Pulmonology

Dr. George Sakoulas is an infectious diseases clinician at Sharp Memorial Hospital in San Diego and professor of pediatrics at the University of California, San Diego School of Medicine. He was the lead investigator in a study published in the May/June 2022 issue of JCOM that found that, when allocated to the appropriate patient type, intravenous immunoglobulin can reduce hospital costs for COVID-19 care. ¹ He joined JCOM’s Editor-in-Chief, Dr. Ebrahim Barkoudah, to discuss the study’s background and highlight its main findings.

The following has been edited for length and clarity.

Dr. Barkoudah Dr. Sakoulas is an investigator and a clinician, bridging both worlds to bring the best evidence to our patients. We’re discussing his new article regarding intravenous immunoglobulin in treating nonventilated COVID-19 patients with moderate-to-severe hypoxia. Dr. Sakoulas, could you please share with our readers the clinical question your study addressed and what your work around COVID-19 management means for clinical practice?

Dr. Sakoulas Thank you. I’m an infectious disease physician. I’ve been treating patients with viral acute respiratory distress syndrome for almost 20 years as an ID doctor. Most of these cases are due to influenza or other viruses. And from time to time, anecdotally and supported by some literature, we’ve been using IVIG, or intravenous immunoglobulin, in some of these cases. And again, I can report anecdotal success with that over the years.

So when COVID emerged in March of 2020, we deployed IVIG in a couple of patients early who were heading downhill. Remember, in March of 2020, we didn’t have the knowledge of steroids helping, patients being ventilated very promptly, and we saw some patients who made a turnaround after treatment with IVIG. We were able to get some support from an industry sponsor and perform and publish a pilot study, enrolling patients early in the pandemic. That study actually showed benefits, which then led the sponsor to fund a phase 3 multicenter clinical trial. Unfortunately, a couple of things happened. First, the trial was designed with the knowledge we had in April of 2020, and again, this is before steroids, before we incorporated proning patients in the ICU, or started ventilating people early. So there were some management changes and evolutions and improvements that happened. And second, the trial was enrolling a very broad repertoire of patients. There were no age limitations, and the trial, ultimately a phase 3 multicenter trial, failed to meet its endpoint.

There were some trends for benefit in younger patients, and as the trial was ongoing, we continued to evolve our knowledge, and we really honed it down to seeing a benefit of using IVIG in patients with COVID with specific criteria in mind. They had to be relatively younger patients, under 65, and not have any major comorbidities. In other words, they weren’t dialysis patients or end-stage disease patients, heart failure patients, cancer or malignancy patients. So, you know, we’re looking at the patients under 65 with obesity, diabetes, and hypertension, who are rapidly declining, going from room air to BiPAP or high-flow oxygen in a short amount of time. And we learned that when using IVIG early, we actually saw patients improve and turn around.

What this article in JCOM highlighted was, number one, incorporating that outcome or that patient type and then looking at the cost of hospitalization of patients who received IVIG versus those that did not. There were 2 groups that were studied. One was the group of patients in that original pilot trial that I discussed who were randomized to receive 1 or the other prospectively; it was an unblinded randomized study. And the second group was a matched case-control study where we had patients treated with IVIG matched by age and comorbidity status and level of hypoxia to patients that did not receive IVIG. We saw a financial benefit in shortening or reducing hospitalizations, really coming down to getting rid of that 20% tail of patients that wound up going to the ICU, getting intubated, and using a high amount of hospital resources that would ramp up the cost of hospitalization. We saw great mitigation of that with IVIG, and even with a small subset of patients, we were able to show a benefit.

Dr. Barkoudah Any thoughts on where we can implement the new findings from your article in our practice at the moment, knowing we now have practice guidelines and protocols to treat COVID-19? There was a tangible benefit in treating the patients the way you approached it in your important work. Could you share with us what would be implementable at the moment?

Dr. Sakoulas I think, fortunately, with the increasing host immunity in the population and decreased virulence of the virus, perhaps we won’t see as many patients of the type that were in these trials going forward, but I suspect we will perhaps in the unvaccinated patients that remain. I believe one-third of the United States is not vaccinated. So there is certainly a vulnerable group of people out there. Potentially, an unvaccinated patient who winds up getting very sick, the patient who is relatively young—what I’m looking at is the 30- to 65-year-old obese, hypertensive, or diabetic patient who comes in and, despite the steroids and the antivirals, rapidly deteriorates into requiring high-flow oxygen. I think implementing IVIG in that patient type would be helpful. I don’t think it’s going to be as helpful in patients who are very elderly, because I think the mechanism of the disease is different in an 80-year-old versus a 50-year-old patient. So again, hopefully, it will not amount to a lot of patients, but I still suspect hospitals are going to see, perhaps in the fall, when they’re expecting a greater number of cases, a trickling of patients that do meet the criteria that I described.

Dr. Barkoudah JCOM’s audience are the QI implementers and hospital leadership. And what caught my eye in your article is your perspective on the pharmacoeconomics of treating COVID-19, and I really appreciate your looking at the cost aspect. Would you talk about the economics of inpatient care, the total care that we provide now that we’re in the age of tocilizumab, and the current state of multiple layers of therapy?

Dr. Sakoulas The reason to look at the economics of it is because IVIG—which is actually not a drug, it’s a blood product—is very expensive. So, we received a considerable amount of administrative pushback implementing this treatment at the beginning outside of the clinical trial setting because it hadn’t been studied on a large scale and because the cost was so high, even though, as a clinician at the bedside, I was seeing a benefit in patients. This study came out of my trying to demonstrate to the folks that are keeping the economics of medicine in mind that, in fact, investing several thousand dollars of treatment in IVIG will save you cost of care, the cost of an ICU bed, the cost of a ventilator, and the cost even of ECMO, which is hugely expensive.

If you look at the numbers in the study, for two-thirds or three-quarters of the patients, your cost of care is actually greater than the controls because you’re giving them IVIG, and it’s increasing the cost of their care, even though three-quarters of the patients are going to do just as well without it. It’s that 20% to 25% of patients that really are going to benefit from it, where you’re reducing your cost of care so much, and you’re getting rid of that very, very expensive 20%, that there’s a cost savings across the board per patient. So, it’s hard to understand when you say you’re losing money on three-quarters of the patients, you’re only saving money on a quarter of the patients, but that cost of saving on that small subset is so substantial it’s really impacting all numbers.

Also, abandoning the outlier principle is sort of an underlying theme in how we think of things. We tend to ignore outliers, not consider them, but I think we really have to pay attention to the more extreme cases because those patients are the ones that drive not just the financial cost of care. Remember, if you’re down to 1 ventilator and you can cut down the use of scarce ICU resources, the cost is sort of even beyond the cost of money. It’s the cost of resources that may become scarce in some settings. So, I think it speaks to that as well.

A lot of the drugs that we use, for example, tocilizumab, were able to be studied in thousands of patients. If you look at the absolute numbers, the benefit of tocilizumab from a magnitude standpoint—low to mid twenties to high twenties—you know, reducing mortality from 29% to 24%. I mean, just take a step back and think about that. Even though it’s statistically significant, try telling a patient, “Well, I’m going to give you this treatment that’s going to reduce mortality from 29% to 24%.” You know, that doesn’t really change anything from a clinical significance standpoint. But they have a P value less than .05, which is our standard, and they were able to do a study with thousands of patients. We didn’t have that luxury with IVIG. No one studied thousands of patients, only retrospectively, and those retrospective studies don’t get the attention because they’re considered biased with all their limitations. But I think one of the difficulties we have here is the balance between statistical and clinical significance. For example, in our pilot study, our ventilation rate was 58% with the non-IVIG patients versus 14% for IVIG patients. So you might say, magnitude-wise, that’s a big number, but the statistical significance of it is borderline because of small numbers.

Anyway, that’s a challenge that we have as clinicians trying to incorporate what’s published—the balancing of statistics, absolute numbers, and practicalities of delivering care. And I think this study highlights some of the nuances that go into that incorporation and those clinical decisions.

Dr. Barkoudah Would you mind sharing with our audience how we can make the connection between the medical outcomes and pharmacoeconomics findings from your article and link it to the bedside and treatment of our patients?

Dr. Sakoulas One of the points this article brings out is the importance of bringing together not just level 1A data, but also small studies with data such as this, where the magnitude of the effect is pretty big but you lose the statistics because of the small numbers. And then also the patients’ aspects of things. I think, as a bedside clinician, you appreciate things, the nuances, much sooner than what percolates out from a level 1A study. Case in point, in the sponsored phase 3 study that we did, and in some other studies that were prospectively done as well, these studies of IVIG simply had an enrollment of patients that was very broad, and not every patient benefits from the same therapy. A great example of this is the sepsis trials with Xigris and those types of agents that failed. You know, there are clinicians to this day who believe that there is a subset of patients that benefit from agents like this. The IVIG story falls a little bit into that category. It comes down to trying to identify the subset of patients that might benefit. And I think we’ve outlined this subset pretty well in our study: the younger, obese diabetic or hypertensive patient who’s rapidly declining.

It really brings together the need to not necessarily toss out these smaller studies, but kind of summarize everything together, and clinicians who are bedside, who are more in tune with the nuances of individual decisions at the individual patient level, might better appreciate these kinds of data. But I think we all have to put it together. IVIG does not make treatment guidelines at national levels and so forth. It’s not even listed in many of them. But there are patients out there who, if you ask them specifically how they felt, including a friend of mine who received the medication, there’s no question from their end, how they felt about this treatment option. Now, some people will get it and will not benefit. We just have to be really tuned into the fact that the same drug does not have the same result for every patient. And just to consider this in the high-risk patients that we talked about in our study.

Dr. Barkoudah While we were prepping for this interview, you made an analogy regarding clinical evidence along the lines of, “Do we need randomized clinical trials to do a parachute-type of experiment,” and we chatted about clinical wisdom. Would you mind sharing with our readers your thoughts on that?

Dr. Sakoulas Sometimes, we try a treatment and it’s very obvious for that particular patient that it helped them. Then you study the treatment in a large trial setting and it doesn’t work. For us bedside clinicians, there are some interventions sometimes that do appear as beneficial as a parachute would be, but yet, there has never been a randomized clinical trial proving that parachutes work. Again, a part of the challenge we have is patients are so different, their immunology is different, the pathogen infecting them is different, the time they present is different. Some present early, some present late. There are just so many moving parts to treating an infection that only a subset of people are going to benefit. And sometimes as clinicians, we’re so nuanced, that we identify a specific subset of patients where we know we can help them. And it’s so obvious for us, like a parachute would be, but to people who are looking at the world from 30,000 feet, they don’t necessarily grasp that because, when you look at all comers, it doesn’t show a benefit.

So the problem is that now those treatments that might help a subset of patients are being denied, and the subset of patients that are going to benefit never get the treatment. Now we have to balance that with a lot of stuff that went on during the pandemic with, you know, ivermectin, hydroxychloroquine, and people pushing those things. Someone asked me once what I thought about hydroxychloroquine, and I said, “Well, somebody in the lab probably showed that it was beneficial, analogous to lighting tissue paper on fire on a plate and taking a cup of water and putting the fire out. Well, now, if you take that cup of water to the Caldor fire that’s burning in California on thousands of acres, you’re not going to be able to put the fire out with that cup of water.” So while it might work in the lab, it’s truly not going to work in a clinical setting. We have to balance individualizing care for patients with some information people are pushing out there that may not be necessarily translatable to the clinical setting.

I think there’s nothing better than being at the bedside, though, and being able to implement something and seeing what works. And really, experience goes a long way in being able to individually treat a patient optimally.

Dr. Barkoudah Thank you for everything you do at the bedside and your work on improving the treatment we have and how we can leverage knowledge to treat our patients. Thank you very much for your time and your scholarly contribution. We appreciate it and I hope the work will continue. We will keep working on treating COVID-19 patients with the best knowledge we have.

Q&A participants: George Sakoulas, MD, Sharp Rees-Stealy Medical Group, La Jolla, CA, and University of California San Diego School of Medicine, San Diego, CA; and Ebrahim Barkoudah, MD, MPH, Department of Medicine, Brigham and Women’s Hospital, Boston, MA.

Disclosures: None reported.

Dr. George Sakoulas is an infectious diseases clinician at Sharp Memorial Hospital in San Diego and professor of pediatrics at the University of California, San Diego School of Medicine. He was the lead investigator in a study published in the May/June 2022 issue of JCOM that found that, when allocated to the appropriate patient type, intravenous immunoglobulin can reduce hospital costs for COVID-19 care. ¹ He joined JCOM’s Editor-in-Chief, Dr. Ebrahim Barkoudah, to discuss the study’s background and highlight its main findings.

The following has been edited for length and clarity.

Dr. Barkoudah Dr. Sakoulas is an investigator and a clinician, bridging both worlds to bring the best evidence to our patients. We’re discussing his new article regarding intravenous immunoglobulin in treating nonventilated COVID-19 patients with moderate-to-severe hypoxia. Dr. Sakoulas, could you please share with our readers the clinical question your study addressed and what your work around COVID-19 management means for clinical practice?

Dr. Sakoulas Thank you. I’m an infectious disease physician. I’ve been treating patients with viral acute respiratory distress syndrome for almost 20 years as an ID doctor. Most of these cases are due to influenza or other viruses. And from time to time, anecdotally and supported by some literature, we’ve been using IVIG, or intravenous immunoglobulin, in some of these cases. And again, I can report anecdotal success with that over the years.

So when COVID emerged in March of 2020, we deployed IVIG in a couple of patients early who were heading downhill. Remember, in March of 2020, we didn’t have the knowledge of steroids helping, patients being ventilated very promptly, and we saw some patients who made a turnaround after treatment with IVIG. We were able to get some support from an industry sponsor and perform and publish a pilot study, enrolling patients early in the pandemic. That study actually showed benefits, which then led the sponsor to fund a phase 3 multicenter clinical trial. Unfortunately, a couple of things happened. First, the trial was designed with the knowledge we had in April of 2020, and again, this is before steroids, before we incorporated proning patients in the ICU, or started ventilating people early. So there were some management changes and evolutions and improvements that happened. And second, the trial was enrolling a very broad repertoire of patients. There were no age limitations, and the trial, ultimately a phase 3 multicenter trial, failed to meet its endpoint.

There were some trends for benefit in younger patients, and as the trial was ongoing, we continued to evolve our knowledge, and we really honed it down to seeing a benefit of using IVIG in patients with COVID with specific criteria in mind. They had to be relatively younger patients, under 65, and not have any major comorbidities. In other words, they weren’t dialysis patients or end-stage disease patients, heart failure patients, cancer or malignancy patients. So, you know, we’re looking at the patients under 65 with obesity, diabetes, and hypertension, who are rapidly declining, going from room air to BiPAP or high-flow oxygen in a short amount of time. And we learned that when using IVIG early, we actually saw patients improve and turn around.

What this article in JCOM highlighted was, number one, incorporating that outcome or that patient type and then looking at the cost of hospitalization of patients who received IVIG versus those that did not. There were 2 groups that were studied. One was the group of patients in that original pilot trial that I discussed who were randomized to receive 1 or the other prospectively; it was an unblinded randomized study. And the second group was a matched case-control study where we had patients treated with IVIG matched by age and comorbidity status and level of hypoxia to patients that did not receive IVIG. We saw a financial benefit in shortening or reducing hospitalizations, really coming down to getting rid of that 20% tail of patients that wound up going to the ICU, getting intubated, and using a high amount of hospital resources that would ramp up the cost of hospitalization. We saw great mitigation of that with IVIG, and even with a small subset of patients, we were able to show a benefit.

Dr. Barkoudah Any thoughts on where we can implement the new findings from your article in our practice at the moment, knowing we now have practice guidelines and protocols to treat COVID-19? There was a tangible benefit in treating the patients the way you approached it in your important work. Could you share with us what would be implementable at the moment?

Dr. Sakoulas I think, fortunately, with the increasing host immunity in the population and decreased virulence of the virus, perhaps we won’t see as many patients of the type that were in these trials going forward, but I suspect we will perhaps in the unvaccinated patients that remain. I believe one-third of the United States is not vaccinated. So there is certainly a vulnerable group of people out there. Potentially, an unvaccinated patient who winds up getting very sick, the patient who is relatively young—what I’m looking at is the 30- to 65-year-old obese, hypertensive, or diabetic patient who comes in and, despite the steroids and the antivirals, rapidly deteriorates into requiring high-flow oxygen. I think implementing IVIG in that patient type would be helpful. I don’t think it’s going to be as helpful in patients who are very elderly, because I think the mechanism of the disease is different in an 80-year-old versus a 50-year-old patient. So again, hopefully, it will not amount to a lot of patients, but I still suspect hospitals are going to see, perhaps in the fall, when they’re expecting a greater number of cases, a trickling of patients that do meet the criteria that I described.

Dr. Barkoudah JCOM’s audience are the QI implementers and hospital leadership. And what caught my eye in your article is your perspective on the pharmacoeconomics of treating COVID-19, and I really appreciate your looking at the cost aspect. Would you talk about the economics of inpatient care, the total care that we provide now that we’re in the age of tocilizumab, and the current state of multiple layers of therapy?

Dr. Sakoulas The reason to look at the economics of it is because IVIG—which is actually not a drug, it’s a blood product—is very expensive. So, we received a considerable amount of administrative pushback implementing this treatment at the beginning outside of the clinical trial setting because it hadn’t been studied on a large scale and because the cost was so high, even though, as a clinician at the bedside, I was seeing a benefit in patients. This study came out of my trying to demonstrate to the folks that are keeping the economics of medicine in mind that, in fact, investing several thousand dollars of treatment in IVIG will save you cost of care, the cost of an ICU bed, the cost of a ventilator, and the cost even of ECMO, which is hugely expensive.

If you look at the numbers in the study, for two-thirds or three-quarters of the patients, your cost of care is actually greater than the controls because you’re giving them IVIG, and it’s increasing the cost of their care, even though three-quarters of the patients are going to do just as well without it. It’s that 20% to 25% of patients that really are going to benefit from it, where you’re reducing your cost of care so much, and you’re getting rid of that very, very expensive 20%, that there’s a cost savings across the board per patient. So, it’s hard to understand when you say you’re losing money on three-quarters of the patients, you’re only saving money on a quarter of the patients, but that cost of saving on that small subset is so substantial it’s really impacting all numbers.

Also, abandoning the outlier principle is sort of an underlying theme in how we think of things. We tend to ignore outliers, not consider them, but I think we really have to pay attention to the more extreme cases because those patients are the ones that drive not just the financial cost of care. Remember, if you’re down to 1 ventilator and you can cut down the use of scarce ICU resources, the cost is sort of even beyond the cost of money. It’s the cost of resources that may become scarce in some settings. So, I think it speaks to that as well.

A lot of the drugs that we use, for example, tocilizumab, were able to be studied in thousands of patients. If you look at the absolute numbers, the benefit of tocilizumab from a magnitude standpoint—low to mid twenties to high twenties—you know, reducing mortality from 29% to 24%. I mean, just take a step back and think about that. Even though it’s statistically significant, try telling a patient, “Well, I’m going to give you this treatment that’s going to reduce mortality from 29% to 24%.” You know, that doesn’t really change anything from a clinical significance standpoint. But they have a P value less than .05, which is our standard, and they were able to do a study with thousands of patients. We didn’t have that luxury with IVIG. No one studied thousands of patients, only retrospectively, and those retrospective studies don’t get the attention because they’re considered biased with all their limitations. But I think one of the difficulties we have here is the balance between statistical and clinical significance. For example, in our pilot study, our ventilation rate was 58% with the non-IVIG patients versus 14% for IVIG patients. So you might say, magnitude-wise, that’s a big number, but the statistical significance of it is borderline because of small numbers.

Anyway, that’s a challenge that we have as clinicians trying to incorporate what’s published—the balancing of statistics, absolute numbers, and practicalities of delivering care. And I think this study highlights some of the nuances that go into that incorporation and those clinical decisions.

Dr. Barkoudah Would you mind sharing with our audience how we can make the connection between the medical outcomes and pharmacoeconomics findings from your article and link it to the bedside and treatment of our patients?

Dr. Sakoulas One of the points this article brings out is the importance of bringing together not just level 1A data, but also small studies with data such as this, where the magnitude of the effect is pretty big but you lose the statistics because of the small numbers. And then also the patients’ aspects of things. I think, as a bedside clinician, you appreciate things, the nuances, much sooner than what percolates out from a level 1A study. Case in point, in the sponsored phase 3 study that we did, and in some other studies that were prospectively done as well, these studies of IVIG simply had an enrollment of patients that was very broad, and not every patient benefits from the same therapy. A great example of this is the sepsis trials with Xigris and those types of agents that failed. You know, there are clinicians to this day who believe that there is a subset of patients that benefit from agents like this. The IVIG story falls a little bit into that category. It comes down to trying to identify the subset of patients that might benefit. And I think we’ve outlined this subset pretty well in our study: the younger, obese diabetic or hypertensive patient who’s rapidly declining.

It really brings together the need to not necessarily toss out these smaller studies, but kind of summarize everything together, and clinicians who are bedside, who are more in tune with the nuances of individual decisions at the individual patient level, might better appreciate these kinds of data. But I think we all have to put it together. IVIG does not make treatment guidelines at national levels and so forth. It’s not even listed in many of them. But there are patients out there who, if you ask them specifically how they felt, including a friend of mine who received the medication, there’s no question from their end, how they felt about this treatment option. Now, some people will get it and will not benefit. We just have to be really tuned into the fact that the same drug does not have the same result for every patient. And just to consider this in the high-risk patients that we talked about in our study.

Dr. Barkoudah While we were prepping for this interview, you made an analogy regarding clinical evidence along the lines of, “Do we need randomized clinical trials to do a parachute-type of experiment,” and we chatted about clinical wisdom. Would you mind sharing with our readers your thoughts on that?

Dr. Sakoulas Sometimes, we try a treatment and it’s very obvious for that particular patient that it helped them. Then you study the treatment in a large trial setting and it doesn’t work. For us bedside clinicians, there are some interventions sometimes that do appear as beneficial as a parachute would be, but yet, there has never been a randomized clinical trial proving that parachutes work. Again, a part of the challenge we have is patients are so different, their immunology is different, the pathogen infecting them is different, the time they present is different. Some present early, some present late. There are just so many moving parts to treating an infection that only a subset of people are going to benefit. And sometimes as clinicians, we’re so nuanced, that we identify a specific subset of patients where we know we can help them. And it’s so obvious for us, like a parachute would be, but to people who are looking at the world from 30,000 feet, they don’t necessarily grasp that because, when you look at all comers, it doesn’t show a benefit.

So the problem is that now those treatments that might help a subset of patients are being denied, and the subset of patients that are going to benefit never get the treatment. Now we have to balance that with a lot of stuff that went on during the pandemic with, you know, ivermectin, hydroxychloroquine, and people pushing those things. Someone asked me once what I thought about hydroxychloroquine, and I said, “Well, somebody in the lab probably showed that it was beneficial, analogous to lighting tissue paper on fire on a plate and taking a cup of water and putting the fire out. Well, now, if you take that cup of water to the Caldor fire that’s burning in California on thousands of acres, you’re not going to be able to put the fire out with that cup of water.” So while it might work in the lab, it’s truly not going to work in a clinical setting. We have to balance individualizing care for patients with some information people are pushing out there that may not be necessarily translatable to the clinical setting.

I think there’s nothing better than being at the bedside, though, and being able to implement something and seeing what works. And really, experience goes a long way in being able to individually treat a patient optimally.

Dr. Barkoudah Thank you for everything you do at the bedside and your work on improving the treatment we have and how we can leverage knowledge to treat our patients. Thank you very much for your time and your scholarly contribution. We appreciate it and I hope the work will continue. We will keep working on treating COVID-19 patients with the best knowledge we have.

Q&A participants: George Sakoulas, MD, Sharp Rees-Stealy Medical Group, La Jolla, CA, and University of California San Diego School of Medicine, San Diego, CA; and Ebrahim Barkoudah, MD, MPH, Department of Medicine, Brigham and Women’s Hospital, Boston, MA.

Disclosures: None reported.

Dr. George Sakoulas is an infectious diseases clinician at Sharp Memorial Hospital in San Diego and professor of pediatrics at the University of California, San Diego School of Medicine. He was the lead investigator in a study published in the May/June 2022 issue of JCOM that found that, when allocated to the appropriate patient type, intravenous immunoglobulin can reduce hospital costs for COVID-19 care. ¹ He joined JCOM’s Editor-in-Chief, Dr. Ebrahim Barkoudah, to discuss the study’s background and highlight its main findings.

The following has been edited for length and clarity.

Dr. Barkoudah Dr. Sakoulas is an investigator and a clinician, bridging both worlds to bring the best evidence to our patients. We’re discussing his new article regarding intravenous immunoglobulin in treating nonventilated COVID-19 patients with moderate-to-severe hypoxia. Dr. Sakoulas, could you please share with our readers the clinical question your study addressed and what your work around COVID-19 management means for clinical practice?

Dr. Sakoulas Thank you. I’m an infectious disease physician. I’ve been treating patients with viral acute respiratory distress syndrome for almost 20 years as an ID doctor. Most of these cases are due to influenza or other viruses. And from time to time, anecdotally and supported by some literature, we’ve been using IVIG, or intravenous immunoglobulin, in some of these cases. And again, I can report anecdotal success with that over the years.

So when COVID emerged in March of 2020, we deployed IVIG in a couple of patients early who were heading downhill. Remember, in March of 2020, we didn’t have the knowledge of steroids helping, patients being ventilated very promptly, and we saw some patients who made a turnaround after treatment with IVIG. We were able to get some support from an industry sponsor and perform and publish a pilot study, enrolling patients early in the pandemic. That study actually showed benefits, which then led the sponsor to fund a phase 3 multicenter clinical trial. Unfortunately, a couple of things happened. First, the trial was designed with the knowledge we had in April of 2020, and again, this is before steroids, before we incorporated proning patients in the ICU, or started ventilating people early. So there were some management changes and evolutions and improvements that happened. And second, the trial was enrolling a very broad repertoire of patients. There were no age limitations, and the trial, ultimately a phase 3 multicenter trial, failed to meet its endpoint.

There were some trends for benefit in younger patients, and as the trial was ongoing, we continued to evolve our knowledge, and we really honed it down to seeing a benefit of using IVIG in patients with COVID with specific criteria in mind. They had to be relatively younger patients, under 65, and not have any major comorbidities. In other words, they weren’t dialysis patients or end-stage disease patients, heart failure patients, cancer or malignancy patients. So, you know, we’re looking at the patients under 65 with obesity, diabetes, and hypertension, who are rapidly declining, going from room air to BiPAP or high-flow oxygen in a short amount of time. And we learned that when using IVIG early, we actually saw patients improve and turn around.

What this article in JCOM highlighted was, number one, incorporating that outcome or that patient type and then looking at the cost of hospitalization of patients who received IVIG versus those that did not. There were 2 groups that were studied. One was the group of patients in that original pilot trial that I discussed who were randomized to receive 1 or the other prospectively; it was an unblinded randomized study. And the second group was a matched case-control study where we had patients treated with IVIG matched by age and comorbidity status and level of hypoxia to patients that did not receive IVIG. We saw a financial benefit in shortening or reducing hospitalizations, really coming down to getting rid of that 20% tail of patients that wound up going to the ICU, getting intubated, and using a high amount of hospital resources that would ramp up the cost of hospitalization. We saw great mitigation of that with IVIG, and even with a small subset of patients, we were able to show a benefit.

Dr. Barkoudah Any thoughts on where we can implement the new findings from your article in our practice at the moment, knowing we now have practice guidelines and protocols to treat COVID-19? There was a tangible benefit in treating the patients the way you approached it in your important work. Could you share with us what would be implementable at the moment?

Dr. Sakoulas I think, fortunately, with the increasing host immunity in the population and decreased virulence of the virus, perhaps we won’t see as many patients of the type that were in these trials going forward, but I suspect we will perhaps in the unvaccinated patients that remain. I believe one-third of the United States is not vaccinated. So there is certainly a vulnerable group of people out there. Potentially, an unvaccinated patient who winds up getting very sick, the patient who is relatively young—what I’m looking at is the 30- to 65-year-old obese, hypertensive, or diabetic patient who comes in and, despite the steroids and the antivirals, rapidly deteriorates into requiring high-flow oxygen. I think implementing IVIG in that patient type would be helpful. I don’t think it’s going to be as helpful in patients who are very elderly, because I think the mechanism of the disease is different in an 80-year-old versus a 50-year-old patient. So again, hopefully, it will not amount to a lot of patients, but I still suspect hospitals are going to see, perhaps in the fall, when they’re expecting a greater number of cases, a trickling of patients that do meet the criteria that I described.

Dr. Barkoudah JCOM’s audience are the QI implementers and hospital leadership. And what caught my eye in your article is your perspective on the pharmacoeconomics of treating COVID-19, and I really appreciate your looking at the cost aspect. Would you talk about the economics of inpatient care, the total care that we provide now that we’re in the age of tocilizumab, and the current state of multiple layers of therapy?

Dr. Sakoulas The reason to look at the economics of it is because IVIG—which is actually not a drug, it’s a blood product—is very expensive. So, we received a considerable amount of administrative pushback implementing this treatment at the beginning outside of the clinical trial setting because it hadn’t been studied on a large scale and because the cost was so high, even though, as a clinician at the bedside, I was seeing a benefit in patients. This study came out of my trying to demonstrate to the folks that are keeping the economics of medicine in mind that, in fact, investing several thousand dollars of treatment in IVIG will save you cost of care, the cost of an ICU bed, the cost of a ventilator, and the cost even of ECMO, which is hugely expensive.

If you look at the numbers in the study, for two-thirds or three-quarters of the patients, your cost of care is actually greater than the controls because you’re giving them IVIG, and it’s increasing the cost of their care, even though three-quarters of the patients are going to do just as well without it. It’s that 20% to 25% of patients that really are going to benefit from it, where you’re reducing your cost of care so much, and you’re getting rid of that very, very expensive 20%, that there’s a cost savings across the board per patient. So, it’s hard to understand when you say you’re losing money on three-quarters of the patients, you’re only saving money on a quarter of the patients, but that cost of saving on that small subset is so substantial it’s really impacting all numbers.

Also, abandoning the outlier principle is sort of an underlying theme in how we think of things. We tend to ignore outliers, not consider them, but I think we really have to pay attention to the more extreme cases because those patients are the ones that drive not just the financial cost of care. Remember, if you’re down to 1 ventilator and you can cut down the use of scarce ICU resources, the cost is sort of even beyond the cost of money. It’s the cost of resources that may become scarce in some settings. So, I think it speaks to that as well.

A lot of the drugs that we use, for example, tocilizumab, were able to be studied in thousands of patients. If you look at the absolute numbers, the benefit of tocilizumab from a magnitude standpoint—low to mid twenties to high twenties—you know, reducing mortality from 29% to 24%. I mean, just take a step back and think about that. Even though it’s statistically significant, try telling a patient, “Well, I’m going to give you this treatment that’s going to reduce mortality from 29% to 24%.” You know, that doesn’t really change anything from a clinical significance standpoint. But they have a P value less than .05, which is our standard, and they were able to do a study with thousands of patients. We didn’t have that luxury with IVIG. No one studied thousands of patients, only retrospectively, and those retrospective studies don’t get the attention because they’re considered biased with all their limitations. But I think one of the difficulties we have here is the balance between statistical and clinical significance. For example, in our pilot study, our ventilation rate was 58% with the non-IVIG patients versus 14% for IVIG patients. So you might say, magnitude-wise, that’s a big number, but the statistical significance of it is borderline because of small numbers.

Anyway, that’s a challenge that we have as clinicians trying to incorporate what’s published—the balancing of statistics, absolute numbers, and practicalities of delivering care. And I think this study highlights some of the nuances that go into that incorporation and those clinical decisions.

Dr. Barkoudah Would you mind sharing with our audience how we can make the connection between the medical outcomes and pharmacoeconomics findings from your article and link it to the bedside and treatment of our patients?

Dr. Sakoulas One of the points this article brings out is the importance of bringing together not just level 1A data, but also small studies with data such as this, where the magnitude of the effect is pretty big but you lose the statistics because of the small numbers. And then also the patients’ aspects of things. I think, as a bedside clinician, you appreciate things, the nuances, much sooner than what percolates out from a level 1A study. Case in point, in the sponsored phase 3 study that we did, and in some other studies that were prospectively done as well, these studies of IVIG simply had an enrollment of patients that was very broad, and not every patient benefits from the same therapy. A great example of this is the sepsis trials with Xigris and those types of agents that failed. You know, there are clinicians to this day who believe that there is a subset of patients that benefit from agents like this. The IVIG story falls a little bit into that category. It comes down to trying to identify the subset of patients that might benefit. And I think we’ve outlined this subset pretty well in our study: the younger, obese diabetic or hypertensive patient who’s rapidly declining.

It really brings together the need to not necessarily toss out these smaller studies, but kind of summarize everything together, and clinicians who are bedside, who are more in tune with the nuances of individual decisions at the individual patient level, might better appreciate these kinds of data. But I think we all have to put it together. IVIG does not make treatment guidelines at national levels and so forth. It’s not even listed in many of them. But there are patients out there who, if you ask them specifically how they felt, including a friend of mine who received the medication, there’s no question from their end, how they felt about this treatment option. Now, some people will get it and will not benefit. We just have to be really tuned into the fact that the same drug does not have the same result for every patient. And just to consider this in the high-risk patients that we talked about in our study.

Dr. Barkoudah While we were prepping for this interview, you made an analogy regarding clinical evidence along the lines of, “Do we need randomized clinical trials to do a parachute-type of experiment,” and we chatted about clinical wisdom. Would you mind sharing with our readers your thoughts on that?

Dr. Sakoulas Sometimes, we try a treatment and it’s very obvious for that particular patient that it helped them. Then you study the treatment in a large trial setting and it doesn’t work. For us bedside clinicians, there are some interventions sometimes that do appear as beneficial as a parachute would be, but yet, there has never been a randomized clinical trial proving that parachutes work. Again, a part of the challenge we have is patients are so different, their immunology is different, the pathogen infecting them is different, the time they present is different. Some present early, some present late. There are just so many moving parts to treating an infection that only a subset of people are going to benefit. And sometimes as clinicians, we’re so nuanced, that we identify a specific subset of patients where we know we can help them. And it’s so obvious for us, like a parachute would be, but to people who are looking at the world from 30,000 feet, they don’t necessarily grasp that because, when you look at all comers, it doesn’t show a benefit.

So the problem is that now those treatments that might help a subset of patients are being denied, and the subset of patients that are going to benefit never get the treatment. Now we have to balance that with a lot of stuff that went on during the pandemic with, you know, ivermectin, hydroxychloroquine, and people pushing those things. Someone asked me once what I thought about hydroxychloroquine, and I said, “Well, somebody in the lab probably showed that it was beneficial, analogous to lighting tissue paper on fire on a plate and taking a cup of water and putting the fire out. Well, now, if you take that cup of water to the Caldor fire that’s burning in California on thousands of acres, you’re not going to be able to put the fire out with that cup of water.” So while it might work in the lab, it’s truly not going to work in a clinical setting. We have to balance individualizing care for patients with some information people are pushing out there that may not be necessarily translatable to the clinical setting.

I think there’s nothing better than being at the bedside, though, and being able to implement something and seeing what works. And really, experience goes a long way in being able to individually treat a patient optimally.

Dr. Barkoudah Thank you for everything you do at the bedside and your work on improving the treatment we have and how we can leverage knowledge to treat our patients. Thank you very much for your time and your scholarly contribution. We appreciate it and I hope the work will continue. We will keep working on treating COVID-19 patients with the best knowledge we have.

Q&A participants: George Sakoulas, MD, Sharp Rees-Stealy Medical Group, La Jolla, CA, and University of California San Diego School of Medicine, San Diego, CA; and Ebrahim Barkoudah, MD, MPH, Department of Medicine, Brigham and Women’s Hospital, Boston, MA.

Disclosures: None reported.

An overreliance on spirometry to identify emphysema led to missed cases in Black individuals, particularly men, based on a secondary data analysis of 2,674 people.

“Over the last few years, there has been growing debate around the use of race adjustment in diagnostic algorithms and equations commonly used in medicine,” lead author Gabrielle Yi-Hui Liu, MD, said in an interview. “Whereas, previously it was common to accept racial or ethnic differences in clinical measures and outcomes as inherent differences among populations, there is now more recognition of how racism, socioeconomic status, and environmental exposures can cause these racial differences. Our initial interest in this study was to examine how the use of race-specific spirometry reference equations, and the use of spirometry in general, may be contributing to racial disparities.”

“Previous studies have suggested that the use of race-specific equations in spirometry can exacerbate racial inequities in healthcare outcomes by under-recognition of early disease in Black adults, and this study adds to that evidence,” said Suman Pal, MBBS, of the University of New Mexico, Albuquerque, in an interview.
“By examining the crucial ways in which systemic factors in medicine, such as race-specific equations, exacerbate racial inequities in healthcare, this study is a timely analysis in a moment of national reckoning of structural racism,” said Dr. Pal, who was not involved in the study.

jgaunion/Thinkstock

In a study published in Annals of Internal Medicine, Dr. Liu and colleagues at Northwestern University, Chicago, conducted a secondary analysis of data from the CARDIA Lung study (Coronary Artery Risk Development In Young Adults).

The primary outcome of the study was the prevalence of emphysema among participants with various measures of normal spirometry results, stratified by sex and race. The normal results included an forced expiratory volume in 1 second (FEV₁₎–forced vital capacity (FVC) ratio greater than or equal to 0.7 or greater than or equal to the lower limit of normal. The participants also were stratified by FEV₁ percent predicted, using race-specific reference equations, for FEV₁ between 80% and 99% of predicted, or an FEV₁ between 100% and 120% of predicted.

The study population included 485 Black men, 762 Black women, 659 White men, and 768 White women who received both a CT scan (in 2010-2011) and spirometry (obtained in 2015-2016) in the CARDIA study. The mean age of the participants at the spirometry exam was 55 years.

A total of 5.3% of the participants had emphysema after stratifying by FEV₁-FVC ratio. The prevalence was significantly higher for Black men, compared with White men (12.3% vs. 4.0%; relative risk, 3.0), and for Black women, compared with White women (5.0% vs. 2.6%; RR, 1.9).

The association between Black race and emphysema risk persisted but decreased when the researchers used a race-neutral estimate.

When the participants were stratified by race-specific FEV₁ percent predicted, 6.5% of individuals with a race-specific FEV₁ between 80% and 99% had emphysema. After controlling for factors including age and smoking, emphysema was significantly more prevalent in Black men versus White men (15.5% vs. 4.0%) and in Black women, compared with White women (6.6% vs. 3.4%).

The racial difference persisted in men with a race-specific FEV₁ between 100% and 120% of predicted. Of these, 4.0% had emphysema. The prevalence was significantly higher in Black men, compared with White men (13.9% vs. 2.2%), but similar between Black women and White women (2.6% vs. 2.0%).

The use of race-neutral equations reduced, but did not eliminate, these disparities, the researchers said.

The findings were limited by the lack of CT imaging data from the same visit as the final spirometry collection, the researchers noted. “Given that imaging was obtained 5 years before spirometry and emphysema is an irreversible finding, this may have led to an overall underestimation of the prevalence of emphysema.”
 

Spirometry alone misses cases

“We were surprised by the substantial rates of emphysema we saw among Black men in our cohort with normal spirometry,” Dr. Liu said in an interview. “We did not expect to find than more than one in eight Black men with an FEV₁ between 100% and 120% predicted would have emphysema – a rate more than six times higher than White men with the same range of FEV₁.”

“One takeaway is that we are likely missing a lot of people with impaired respiratory health or true lung disease by only using spirometry to diagnose COPD,” said Dr. Liu. In clinical practice, “physicians should consider ordering CT scans on patients with normal spirometry who have respiratory symptoms such as cough or shortness of breath. If emphysema is found, physicians should discuss mitigating any potential risk factors and consider the use of COPD medications such as inhalers.

“Our findings also support using race-neutral reference equations to interpret spirometry instead of race-specific equations. Racial disparities in rates of emphysema among those with ‘normal’ FEV₁ [between 80% and 120% predicted], were attenuated or eliminated when race-neutral equations were used to calculate FEV₁. This suggests that race-specific equations are normalizing worse lung health in Black adults,” Dr. Liu explained.

“We need to continue research into additional tools that can be used to assess respiratory health and diagnose COPD, while keeping in mind how these tools may affect racial disparities,” said Dr. Liu. “Our study suggests that our reliance on spirometry measures such as FEV₁/FVC ratio and FEV₁ is missing a number of people with respiratory symptoms and CT evidence of lung disease, and that this is disproportionately affecting Black adults in the United States.” Looking ahead, “it is important to find better tools to identify people with impaired respiratory health or early manifestations of disease so we can intercept chronic lung disease before it becomes clinically apparent and patients have sustained significant lung damage.”

The CARDIA study was supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Dr. Liu was supported by a grant from the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Pal had no financial conflicts to disclose.

*This article was updated 7/22/2022.

An overreliance on spirometry to identify emphysema led to missed cases in Black individuals, particularly men, based on a secondary data analysis of 2,674 people.

“Over the last few years, there has been growing debate around the use of race adjustment in diagnostic algorithms and equations commonly used in medicine,” lead author Gabrielle Yi-Hui Liu, MD, said in an interview. “Whereas, previously it was common to accept racial or ethnic differences in clinical measures and outcomes as inherent differences among populations, there is now more recognition of how racism, socioeconomic status, and environmental exposures can cause these racial differences. Our initial interest in this study was to examine how the use of race-specific spirometry reference equations, and the use of spirometry in general, may be contributing to racial disparities.”

“Previous studies have suggested that the use of race-specific equations in spirometry can exacerbate racial inequities in healthcare outcomes by under-recognition of early disease in Black adults, and this study adds to that evidence,” said Suman Pal, MBBS, of the University of New Mexico, Albuquerque, in an interview.
“By examining the crucial ways in which systemic factors in medicine, such as race-specific equations, exacerbate racial inequities in healthcare, this study is a timely analysis in a moment of national reckoning of structural racism,” said Dr. Pal, who was not involved in the study.

jgaunion/Thinkstock

In a study published in Annals of Internal Medicine, Dr. Liu and colleagues at Northwestern University, Chicago, conducted a secondary analysis of data from the CARDIA Lung study (Coronary Artery Risk Development In Young Adults).

The primary outcome of the study was the prevalence of emphysema among participants with various measures of normal spirometry results, stratified by sex and race. The normal results included an forced expiratory volume in 1 second (FEV₁₎–forced vital capacity (FVC) ratio greater than or equal to 0.7 or greater than or equal to the lower limit of normal. The participants also were stratified by FEV₁ percent predicted, using race-specific reference equations, for FEV₁ between 80% and 99% of predicted, or an FEV₁ between 100% and 120% of predicted.

The study population included 485 Black men, 762 Black women, 659 White men, and 768 White women who received both a CT scan (in 2010-2011) and spirometry (obtained in 2015-2016) in the CARDIA study. The mean age of the participants at the spirometry exam was 55 years.

A total of 5.3% of the participants had emphysema after stratifying by FEV₁-FVC ratio. The prevalence was significantly higher for Black men, compared with White men (12.3% vs. 4.0%; relative risk, 3.0), and for Black women, compared with White women (5.0% vs. 2.6%; RR, 1.9).

The association between Black race and emphysema risk persisted but decreased when the researchers used a race-neutral estimate.

When the participants were stratified by race-specific FEV₁ percent predicted, 6.5% of individuals with a race-specific FEV₁ between 80% and 99% had emphysema. After controlling for factors including age and smoking, emphysema was significantly more prevalent in Black men versus White men (15.5% vs. 4.0%) and in Black women, compared with White women (6.6% vs. 3.4%).

The racial difference persisted in men with a race-specific FEV₁ between 100% and 120% of predicted. Of these, 4.0% had emphysema. The prevalence was significantly higher in Black men, compared with White men (13.9% vs. 2.2%), but similar between Black women and White women (2.6% vs. 2.0%).

The use of race-neutral equations reduced, but did not eliminate, these disparities, the researchers said.

The findings were limited by the lack of CT imaging data from the same visit as the final spirometry collection, the researchers noted. “Given that imaging was obtained 5 years before spirometry and emphysema is an irreversible finding, this may have led to an overall underestimation of the prevalence of emphysema.”
 

Spirometry alone misses cases

“We were surprised by the substantial rates of emphysema we saw among Black men in our cohort with normal spirometry,” Dr. Liu said in an interview. “We did not expect to find than more than one in eight Black men with an FEV₁ between 100% and 120% predicted would have emphysema – a rate more than six times higher than White men with the same range of FEV₁.”

“One takeaway is that we are likely missing a lot of people with impaired respiratory health or true lung disease by only using spirometry to diagnose COPD,” said Dr. Liu. In clinical practice, “physicians should consider ordering CT scans on patients with normal spirometry who have respiratory symptoms such as cough or shortness of breath. If emphysema is found, physicians should discuss mitigating any potential risk factors and consider the use of COPD medications such as inhalers.

“Our findings also support using race-neutral reference equations to interpret spirometry instead of race-specific equations. Racial disparities in rates of emphysema among those with ‘normal’ FEV₁ [between 80% and 120% predicted], were attenuated or eliminated when race-neutral equations were used to calculate FEV₁. This suggests that race-specific equations are normalizing worse lung health in Black adults,” Dr. Liu explained.

“We need to continue research into additional tools that can be used to assess respiratory health and diagnose COPD, while keeping in mind how these tools may affect racial disparities,” said Dr. Liu. “Our study suggests that our reliance on spirometry measures such as FEV₁/FVC ratio and FEV₁ is missing a number of people with respiratory symptoms and CT evidence of lung disease, and that this is disproportionately affecting Black adults in the United States.” Looking ahead, “it is important to find better tools to identify people with impaired respiratory health or early manifestations of disease so we can intercept chronic lung disease before it becomes clinically apparent and patients have sustained significant lung damage.”

The CARDIA study was supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Dr. Liu was supported by a grant from the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Pal had no financial conflicts to disclose.

*This article was updated 7/22/2022.

An overreliance on spirometry to identify emphysema led to missed cases in Black individuals, particularly men, based on a secondary data analysis of 2,674 people.

“Over the last few years, there has been growing debate around the use of race adjustment in diagnostic algorithms and equations commonly used in medicine,” lead author Gabrielle Yi-Hui Liu, MD, said in an interview. “Whereas, previously it was common to accept racial or ethnic differences in clinical measures and outcomes as inherent differences among populations, there is now more recognition of how racism, socioeconomic status, and environmental exposures can cause these racial differences. Our initial interest in this study was to examine how the use of race-specific spirometry reference equations, and the use of spirometry in general, may be contributing to racial disparities.”

“Previous studies have suggested that the use of race-specific equations in spirometry can exacerbate racial inequities in healthcare outcomes by under-recognition of early disease in Black adults, and this study adds to that evidence,” said Suman Pal, MBBS, of the University of New Mexico, Albuquerque, in an interview.
“By examining the crucial ways in which systemic factors in medicine, such as race-specific equations, exacerbate racial inequities in healthcare, this study is a timely analysis in a moment of national reckoning of structural racism,” said Dr. Pal, who was not involved in the study.

jgaunion/Thinkstock

In a study published in Annals of Internal Medicine, Dr. Liu and colleagues at Northwestern University, Chicago, conducted a secondary analysis of data from the CARDIA Lung study (Coronary Artery Risk Development In Young Adults).

The primary outcome of the study was the prevalence of emphysema among participants with various measures of normal spirometry results, stratified by sex and race. The normal results included an forced expiratory volume in 1 second (FEV₁₎–forced vital capacity (FVC) ratio greater than or equal to 0.7 or greater than or equal to the lower limit of normal. The participants also were stratified by FEV₁ percent predicted, using race-specific reference equations, for FEV₁ between 80% and 99% of predicted, or an FEV₁ between 100% and 120% of predicted.

The study population included 485 Black men, 762 Black women, 659 White men, and 768 White women who received both a CT scan (in 2010-2011) and spirometry (obtained in 2015-2016) in the CARDIA study. The mean age of the participants at the spirometry exam was 55 years.

A total of 5.3% of the participants had emphysema after stratifying by FEV₁-FVC ratio. The prevalence was significantly higher for Black men, compared with White men (12.3% vs. 4.0%; relative risk, 3.0), and for Black women, compared with White women (5.0% vs. 2.6%; RR, 1.9).

The association between Black race and emphysema risk persisted but decreased when the researchers used a race-neutral estimate.

When the participants were stratified by race-specific FEV₁ percent predicted, 6.5% of individuals with a race-specific FEV₁ between 80% and 99% had emphysema. After controlling for factors including age and smoking, emphysema was significantly more prevalent in Black men versus White men (15.5% vs. 4.0%) and in Black women, compared with White women (6.6% vs. 3.4%).

The racial difference persisted in men with a race-specific FEV₁ between 100% and 120% of predicted. Of these, 4.0% had emphysema. The prevalence was significantly higher in Black men, compared with White men (13.9% vs. 2.2%), but similar between Black women and White women (2.6% vs. 2.0%).

The use of race-neutral equations reduced, but did not eliminate, these disparities, the researchers said.

The findings were limited by the lack of CT imaging data from the same visit as the final spirometry collection, the researchers noted. “Given that imaging was obtained 5 years before spirometry and emphysema is an irreversible finding, this may have led to an overall underestimation of the prevalence of emphysema.”
 

Spirometry alone misses cases

“We were surprised by the substantial rates of emphysema we saw among Black men in our cohort with normal spirometry,” Dr. Liu said in an interview. “We did not expect to find than more than one in eight Black men with an FEV₁ between 100% and 120% predicted would have emphysema – a rate more than six times higher than White men with the same range of FEV₁.”

“One takeaway is that we are likely missing a lot of people with impaired respiratory health or true lung disease by only using spirometry to diagnose COPD,” said Dr. Liu. In clinical practice, “physicians should consider ordering CT scans on patients with normal spirometry who have respiratory symptoms such as cough or shortness of breath. If emphysema is found, physicians should discuss mitigating any potential risk factors and consider the use of COPD medications such as inhalers.

“Our findings also support using race-neutral reference equations to interpret spirometry instead of race-specific equations. Racial disparities in rates of emphysema among those with ‘normal’ FEV₁ [between 80% and 120% predicted], were attenuated or eliminated when race-neutral equations were used to calculate FEV₁. This suggests that race-specific equations are normalizing worse lung health in Black adults,” Dr. Liu explained.

“We need to continue research into additional tools that can be used to assess respiratory health and diagnose COPD, while keeping in mind how these tools may affect racial disparities,” said Dr. Liu. “Our study suggests that our reliance on spirometry measures such as FEV₁/FVC ratio and FEV₁ is missing a number of people with respiratory symptoms and CT evidence of lung disease, and that this is disproportionately affecting Black adults in the United States.” Looking ahead, “it is important to find better tools to identify people with impaired respiratory health or early manifestations of disease so we can intercept chronic lung disease before it becomes clinically apparent and patients have sustained significant lung damage.”

The CARDIA study was supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Dr. Liu was supported by a grant from the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Pal had no financial conflicts to disclose.

*This article was updated 7/22/2022.

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Right ventricular (RV) dilation or dysfunction in patients hospitalized with acute COVID-19 is associated with an elevated risk for in-hospital death.
• The impact of RV dilation or dysfunction on in-hospital mortality is similar for patients with acute COVID-19 and those with influenza, pneumonia, or acute respiratory distress syndrome (ARDS), but COVID-19 patients have greater absolute in-hospital mortality.
• RV dilatation or dysfunction in patients with acute COVID-19 is associated with a diagnosis of venous thromboembolism and subsequent intubation and mechanical ventilation.

Why this matters

• Right ventricular dysfunction increases mortality risk in acute COVID-19, and this study shows that RV dilation and dysfunction among such hospitalized patients has a similar impact on risk for in-hospital death in acute COVID-19 and in other respiratory illnesses.
• The findings suggest that abnormal RV findings should be considered a mortality risk marker in patients with acute respiratory illness, especially COVID-19.

Study design

• The retrospective study involved 225 consecutive patients admitted for acute COVID-19 from March 2020 to February 2021 at four major hospitals in the same metropolitan region and a control group of 6,150 adults admitted to the hospital for influenza, pneumonia, or ARDS; mean age in the study cohort was 63 years.
• All participants underwent echocardiography during their hospitalization, including evaluation of any RV dilation or dysfunction.
• Associations between RV measurements and in-hospital mortality, the primary outcome, were adjusted for potential confounders.

Key results

• Patients in the COVID-19 group were more likely than were those in the control group to be male (66% vs. 54%; P < .001), to identify as Hispanic (38% vs. 15%; P < .001), and to have a higher mean body mass index (29.4 vs. 27.9 kg/m²; P = .008).
• Compared with the control group, patients in the COVID-19 group more often required admission to the intensive care unit (75% vs. 54%; P < .001), mechanical ventilation (P < .001), and initiation of renal replacement therapy (P = .002), and more often were diagnosed with deep-vein thrombosis or pulmonary embolism (25% vs. 14%; P < .001). The median length of hospital stay was 20 days in the COVID-19 group, compared with 10 days in the control group (P < .001).
• In-hospital mortality was 21.3% in the COVID-19 group and 11.8% in the control group (P = .001). Those hospitalized with COVID-19 had an adjusted relative risk (RR) of 1.54 (95% confidence interval [CI], 1.06-2.24; P = .02) for in-hospital mortality, compared with those hospitalized for other respiratory illnesses.
• Mild RV dilation was associated with an adjusted RR of 1.4 (95% CI, 1.17-1.69; P = .0003) for in-hospital death, and moderate to severe RV dilation was associated with an adjusted RR of 2.0 (95% CI, 1.62-2.47; P < .0001).
• The corresponding adjusted risks for mild RV dysfunction and greater-than-mild RV dysfunction were, respectively, 1.39 (95% CI, 1.10-1.77; P = .007) and 1.68 (95% CI, 1.17-2.42; P = .005).
• The RR for in-hospital mortality associated with RV dilation and dysfunction was similar in those with COVID-19 and those with other respiratory illness, but the former had a higher baseline risk that yielded a greater absolute risk in the COVID-19 group.

Limitations

• The study was based primarily on a retrospective review of electronic health records, which poses a risk for misclassification. 
• Echocardiography was performed without blinding operators to patient clinical status, and echocardiograms were interpreted in a single university hospital system, so were not externally validated.
• Because echocardiograms obtained during hospitalization could not be compared with previous echocardiograms, it could not be determined whether any of the patients had preexisting RV dilation or dysfunction.
• Strain imaging was not feasible in many cases.

Disclosures

• The study received no commercial funding.
• The authors disclosed no financial relationships.

This is a summary of a preprint research study, Association of Right Ventricular Dilation and Dysfunction on Echocardiogram With In-Hospital Mortality Among Patients Hospitalized with COVID-19 Compared With Other Acute Respiratory Illness, written by researchers at the University of California, San Francisco, department of medicine, and Zuckerberg San Francisco General Hospital, division of cardiology. A version of this article first appeared on Medscape.com.

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Right ventricular (RV) dilation or dysfunction in patients hospitalized with acute COVID-19 is associated with an elevated risk for in-hospital death.
• The impact of RV dilation or dysfunction on in-hospital mortality is similar for patients with acute COVID-19 and those with influenza, pneumonia, or acute respiratory distress syndrome (ARDS), but COVID-19 patients have greater absolute in-hospital mortality.
• RV dilatation or dysfunction in patients with acute COVID-19 is associated with a diagnosis of venous thromboembolism and subsequent intubation and mechanical ventilation.

Why this matters

• Right ventricular dysfunction increases mortality risk in acute COVID-19, and this study shows that RV dilation and dysfunction among such hospitalized patients has a similar impact on risk for in-hospital death in acute COVID-19 and in other respiratory illnesses.
• The findings suggest that abnormal RV findings should be considered a mortality risk marker in patients with acute respiratory illness, especially COVID-19.

Study design

• The retrospective study involved 225 consecutive patients admitted for acute COVID-19 from March 2020 to February 2021 at four major hospitals in the same metropolitan region and a control group of 6,150 adults admitted to the hospital for influenza, pneumonia, or ARDS; mean age in the study cohort was 63 years.
• All participants underwent echocardiography during their hospitalization, including evaluation of any RV dilation or dysfunction.
• Associations between RV measurements and in-hospital mortality, the primary outcome, were adjusted for potential confounders.

Key results

• Patients in the COVID-19 group were more likely than were those in the control group to be male (66% vs. 54%; P < .001), to identify as Hispanic (38% vs. 15%; P < .001), and to have a higher mean body mass index (29.4 vs. 27.9 kg/m²; P = .008).
• Compared with the control group, patients in the COVID-19 group more often required admission to the intensive care unit (75% vs. 54%; P < .001), mechanical ventilation (P < .001), and initiation of renal replacement therapy (P = .002), and more often were diagnosed with deep-vein thrombosis or pulmonary embolism (25% vs. 14%; P < .001). The median length of hospital stay was 20 days in the COVID-19 group, compared with 10 days in the control group (P < .001).
• In-hospital mortality was 21.3% in the COVID-19 group and 11.8% in the control group (P = .001). Those hospitalized with COVID-19 had an adjusted relative risk (RR) of 1.54 (95% confidence interval [CI], 1.06-2.24; P = .02) for in-hospital mortality, compared with those hospitalized for other respiratory illnesses.
• Mild RV dilation was associated with an adjusted RR of 1.4 (95% CI, 1.17-1.69; P = .0003) for in-hospital death, and moderate to severe RV dilation was associated with an adjusted RR of 2.0 (95% CI, 1.62-2.47; P < .0001).
• The corresponding adjusted risks for mild RV dysfunction and greater-than-mild RV dysfunction were, respectively, 1.39 (95% CI, 1.10-1.77; P = .007) and 1.68 (95% CI, 1.17-2.42; P = .005).
• The RR for in-hospital mortality associated with RV dilation and dysfunction was similar in those with COVID-19 and those with other respiratory illness, but the former had a higher baseline risk that yielded a greater absolute risk in the COVID-19 group.

Limitations

• The study was based primarily on a retrospective review of electronic health records, which poses a risk for misclassification. 
• Echocardiography was performed without blinding operators to patient clinical status, and echocardiograms were interpreted in a single university hospital system, so were not externally validated.
• Because echocardiograms obtained during hospitalization could not be compared with previous echocardiograms, it could not be determined whether any of the patients had preexisting RV dilation or dysfunction.
• Strain imaging was not feasible in many cases.

Disclosures

• The study received no commercial funding.
• The authors disclosed no financial relationships.

This is a summary of a preprint research study, Association of Right Ventricular Dilation and Dysfunction on Echocardiogram With In-Hospital Mortality Among Patients Hospitalized with COVID-19 Compared With Other Acute Respiratory Illness, written by researchers at the University of California, San Francisco, department of medicine, and Zuckerberg San Francisco General Hospital, division of cardiology. A version of this article first appeared on Medscape.com.

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Right ventricular (RV) dilation or dysfunction in patients hospitalized with acute COVID-19 is associated with an elevated risk for in-hospital death.
• The impact of RV dilation or dysfunction on in-hospital mortality is similar for patients with acute COVID-19 and those with influenza, pneumonia, or acute respiratory distress syndrome (ARDS), but COVID-19 patients have greater absolute in-hospital mortality.
• RV dilatation or dysfunction in patients with acute COVID-19 is associated with a diagnosis of venous thromboembolism and subsequent intubation and mechanical ventilation.

Why this matters

• Right ventricular dysfunction increases mortality risk in acute COVID-19, and this study shows that RV dilation and dysfunction among such hospitalized patients has a similar impact on risk for in-hospital death in acute COVID-19 and in other respiratory illnesses.
• The findings suggest that abnormal RV findings should be considered a mortality risk marker in patients with acute respiratory illness, especially COVID-19.

Study design

• The retrospective study involved 225 consecutive patients admitted for acute COVID-19 from March 2020 to February 2021 at four major hospitals in the same metropolitan region and a control group of 6,150 adults admitted to the hospital for influenza, pneumonia, or ARDS; mean age in the study cohort was 63 years.
• All participants underwent echocardiography during their hospitalization, including evaluation of any RV dilation or dysfunction.
• Associations between RV measurements and in-hospital mortality, the primary outcome, were adjusted for potential confounders.

Key results

• Patients in the COVID-19 group were more likely than were those in the control group to be male (66% vs. 54%; P < .001), to identify as Hispanic (38% vs. 15%; P < .001), and to have a higher mean body mass index (29.4 vs. 27.9 kg/m²; P = .008).
• Compared with the control group, patients in the COVID-19 group more often required admission to the intensive care unit (75% vs. 54%; P < .001), mechanical ventilation (P < .001), and initiation of renal replacement therapy (P = .002), and more often were diagnosed with deep-vein thrombosis or pulmonary embolism (25% vs. 14%; P < .001). The median length of hospital stay was 20 days in the COVID-19 group, compared with 10 days in the control group (P < .001).
• In-hospital mortality was 21.3% in the COVID-19 group and 11.8% in the control group (P = .001). Those hospitalized with COVID-19 had an adjusted relative risk (RR) of 1.54 (95% confidence interval [CI], 1.06-2.24; P = .02) for in-hospital mortality, compared with those hospitalized for other respiratory illnesses.
• Mild RV dilation was associated with an adjusted RR of 1.4 (95% CI, 1.17-1.69; P = .0003) for in-hospital death, and moderate to severe RV dilation was associated with an adjusted RR of 2.0 (95% CI, 1.62-2.47; P < .0001).
• The corresponding adjusted risks for mild RV dysfunction and greater-than-mild RV dysfunction were, respectively, 1.39 (95% CI, 1.10-1.77; P = .007) and 1.68 (95% CI, 1.17-2.42; P = .005).
• The RR for in-hospital mortality associated with RV dilation and dysfunction was similar in those with COVID-19 and those with other respiratory illness, but the former had a higher baseline risk that yielded a greater absolute risk in the COVID-19 group.

Limitations

• The study was based primarily on a retrospective review of electronic health records, which poses a risk for misclassification. 
• Echocardiography was performed without blinding operators to patient clinical status, and echocardiograms were interpreted in a single university hospital system, so were not externally validated.
• Because echocardiograms obtained during hospitalization could not be compared with previous echocardiograms, it could not be determined whether any of the patients had preexisting RV dilation or dysfunction.
• Strain imaging was not feasible in many cases.

Disclosures

• The study received no commercial funding.
• The authors disclosed no financial relationships.

This is a summary of a preprint research study, Association of Right Ventricular Dilation and Dysfunction on Echocardiogram With In-Hospital Mortality Among Patients Hospitalized with COVID-19 Compared With Other Acute Respiratory Illness, written by researchers at the University of California, San Francisco, department of medicine, and Zuckerberg San Francisco General Hospital, division of cardiology. A version of this article first appeared on Medscape.com.

Differences in the safety and efficacy between the biologics approved for the treatment of severe eosinophilic asthma are so minimal as to not meet clinically important thresholds, a network meta-analysis shows.

“We know relatively little of the comparative effectiveness or safety of biologics approved for the treatment of asthma [but since] the number of these biologics continue to rise and their indications are increasing, the opportunities to use these biologics will only continue to increase, and we need to know more about their comparative effectiveness to optimize their use,” Ayobami Akenroye, MD, MPH, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said in an interview.

“But the decision to use one biologic or not is complex and goes beyond comparative effectiveness, and factors such as insurance coverage, convenience of self-administration, and comorbidities all play a role in the choice of biologics,” she said, adding that all the outcomes assessed in the study contribute to or reflect a patient’s underlying asthma control.

The study was published online in the Journal of Allergy and Clinical Immunology.
 

Interleukin pathways

Drugs that target various interleukin signaling pathways involved in the pathogenesis of asthma include mepolizumab (Nucala), benralizumab (Fasenra), and dupilumab (Dupixent), all of which have been shown to decrease exacerbation rates, improve lung function, and enhance quality of life for patients with severe eosinophilic asthma. In a Bayesian network meta-analysis that allows for simultaneous comparisons of these three treatments, investigators analyzed eight randomized, placebo-controlled trials that compared each of the drugs with placebo. In total, the trials involved 6,461 patients; the duration of follow-up was between 24 and 56 weeks.

“In the subgroup of patients with eosinophil counts of ≥ 300 cells/mcL, all three biologics were significantly better than placebo in reducing exacerbations,” Dr. Akenroye and colleagues reported. For example, dupilumab reduced the exacerbation risk by 68% at a risk ratio of 0.32 (95% confidence interval, 0.23-0.45), while mepolizumab reduced it by almost as much at 63% (RR, 0.37; 95% CI, 0.30-0.45).

Benralizumab was slightly less effective than the other two biologics, reducing exacerbation risk by 51% (RR, 0.49; 95% CI, 0.43-0.55). “In patients with eosinophil counts of ≥ 300 cells/mcL, all three biologics had a probability of 1 in improving the exacerbation rate by 20% or more ... in comparison to placebo,” the authors wrote.

Regarding each drug’s effect in improving forced expiratory volume in 1 second (FEV₁), the mean difference in milliliters with dupilumab before and after treatment was 230 (95% CI, 160-300), while for benralizumab, the MD was 150 (95% CI, 100-220) before and after treatment. With mepolizumab, the MD in FEV₁ before and after treatment was also 150. In the same subgroup of patients with eosinophil counts of at least300 cells/mcL, all three biologics again had a probability of 1 in improving FEV₁ by 50 mL or more above the placebo effect. A third endpoint that was analyzed was the potential reduction in asthma control questionnaire (ACQ) scores. With mepolizumab, the MD before and after treatment was –0.65 (95% CI, –0.81 to –0.45); with dupilumab, it was –0.48 (95% CI, –0.83 to –0.14); and with dupilumab, it was –0.32 (95% CI, –0.43 to –0.21).

“Dupilumab was significantly better than benralizumab in improving exacerbations,” the authors noted (RR, 0.66; 95% CI, 0.47-0.94), while mepolizumab was also better than benralizumab (RR, 0.75; 95% CI, 0.60-0.95). On the other hand, both dupilumab and benralizumab led to greater improvements in FEV₁ than mepolizumab, although the effects of dupilumab and benralizumab on ACQ scores were not significantly different for patients whose lower eosinophil counts were between 150 and 299 cells/mcL.

As for safety outcomes, both mepolizumab and benralizumab were associated with a lower risk of serious adverse events, but dupilumab was not different from placebo in terms of overall safety, according to the authors. “The ultimate choice of biologic for each patient would ... depend on multiple factors including cost considerations and timing of administration.

“[However], these results may be helpful to clinicians as they optimize patient care,” they concluded. Limitations to the analysis include the fact that indirect comparisons cannot replace randomized trials that compare the three drugs directly.

It’s estimated that 5%-10% of the 26 million individuals with asthma in the United States have severe disease.

Dr. Akenroye disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Differences in the safety and efficacy between the biologics approved for the treatment of severe eosinophilic asthma are so minimal as to not meet clinically important thresholds, a network meta-analysis shows.

“We know relatively little of the comparative effectiveness or safety of biologics approved for the treatment of asthma [but since] the number of these biologics continue to rise and their indications are increasing, the opportunities to use these biologics will only continue to increase, and we need to know more about their comparative effectiveness to optimize their use,” Ayobami Akenroye, MD, MPH, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said in an interview.

“But the decision to use one biologic or not is complex and goes beyond comparative effectiveness, and factors such as insurance coverage, convenience of self-administration, and comorbidities all play a role in the choice of biologics,” she said, adding that all the outcomes assessed in the study contribute to or reflect a patient’s underlying asthma control.

The study was published online in the Journal of Allergy and Clinical Immunology.
 

Interleukin pathways

Drugs that target various interleukin signaling pathways involved in the pathogenesis of asthma include mepolizumab (Nucala), benralizumab (Fasenra), and dupilumab (Dupixent), all of which have been shown to decrease exacerbation rates, improve lung function, and enhance quality of life for patients with severe eosinophilic asthma. In a Bayesian network meta-analysis that allows for simultaneous comparisons of these three treatments, investigators analyzed eight randomized, placebo-controlled trials that compared each of the drugs with placebo. In total, the trials involved 6,461 patients; the duration of follow-up was between 24 and 56 weeks.

“In the subgroup of patients with eosinophil counts of ≥ 300 cells/mcL, all three biologics were significantly better than placebo in reducing exacerbations,” Dr. Akenroye and colleagues reported. For example, dupilumab reduced the exacerbation risk by 68% at a risk ratio of 0.32 (95% confidence interval, 0.23-0.45), while mepolizumab reduced it by almost as much at 63% (RR, 0.37; 95% CI, 0.30-0.45).

Benralizumab was slightly less effective than the other two biologics, reducing exacerbation risk by 51% (RR, 0.49; 95% CI, 0.43-0.55). “In patients with eosinophil counts of ≥ 300 cells/mcL, all three biologics had a probability of 1 in improving the exacerbation rate by 20% or more ... in comparison to placebo,” the authors wrote.

Regarding each drug’s effect in improving forced expiratory volume in 1 second (FEV₁), the mean difference in milliliters with dupilumab before and after treatment was 230 (95% CI, 160-300), while for benralizumab, the MD was 150 (95% CI, 100-220) before and after treatment. With mepolizumab, the MD in FEV₁ before and after treatment was also 150. In the same subgroup of patients with eosinophil counts of at least300 cells/mcL, all three biologics again had a probability of 1 in improving FEV₁ by 50 mL or more above the placebo effect. A third endpoint that was analyzed was the potential reduction in asthma control questionnaire (ACQ) scores. With mepolizumab, the MD before and after treatment was –0.65 (95% CI, –0.81 to –0.45); with dupilumab, it was –0.48 (95% CI, –0.83 to –0.14); and with dupilumab, it was –0.32 (95% CI, –0.43 to –0.21).

“Dupilumab was significantly better than benralizumab in improving exacerbations,” the authors noted (RR, 0.66; 95% CI, 0.47-0.94), while mepolizumab was also better than benralizumab (RR, 0.75; 95% CI, 0.60-0.95). On the other hand, both dupilumab and benralizumab led to greater improvements in FEV₁ than mepolizumab, although the effects of dupilumab and benralizumab on ACQ scores were not significantly different for patients whose lower eosinophil counts were between 150 and 299 cells/mcL.

As for safety outcomes, both mepolizumab and benralizumab were associated with a lower risk of serious adverse events, but dupilumab was not different from placebo in terms of overall safety, according to the authors. “The ultimate choice of biologic for each patient would ... depend on multiple factors including cost considerations and timing of administration.

“[However], these results may be helpful to clinicians as they optimize patient care,” they concluded. Limitations to the analysis include the fact that indirect comparisons cannot replace randomized trials that compare the three drugs directly.

It’s estimated that 5%-10% of the 26 million individuals with asthma in the United States have severe disease.

Dr. Akenroye disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Differences in the safety and efficacy between the biologics approved for the treatment of severe eosinophilic asthma are so minimal as to not meet clinically important thresholds, a network meta-analysis shows.

“We know relatively little of the comparative effectiveness or safety of biologics approved for the treatment of asthma [but since] the number of these biologics continue to rise and their indications are increasing, the opportunities to use these biologics will only continue to increase, and we need to know more about their comparative effectiveness to optimize their use,” Ayobami Akenroye, MD, MPH, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said in an interview.

“But the decision to use one biologic or not is complex and goes beyond comparative effectiveness, and factors such as insurance coverage, convenience of self-administration, and comorbidities all play a role in the choice of biologics,” she said, adding that all the outcomes assessed in the study contribute to or reflect a patient’s underlying asthma control.

The study was published online in the Journal of Allergy and Clinical Immunology.
 

Interleukin pathways

Drugs that target various interleukin signaling pathways involved in the pathogenesis of asthma include mepolizumab (Nucala), benralizumab (Fasenra), and dupilumab (Dupixent), all of which have been shown to decrease exacerbation rates, improve lung function, and enhance quality of life for patients with severe eosinophilic asthma. In a Bayesian network meta-analysis that allows for simultaneous comparisons of these three treatments, investigators analyzed eight randomized, placebo-controlled trials that compared each of the drugs with placebo. In total, the trials involved 6,461 patients; the duration of follow-up was between 24 and 56 weeks.

“In the subgroup of patients with eosinophil counts of ≥ 300 cells/mcL, all three biologics were significantly better than placebo in reducing exacerbations,” Dr. Akenroye and colleagues reported. For example, dupilumab reduced the exacerbation risk by 68% at a risk ratio of 0.32 (95% confidence interval, 0.23-0.45), while mepolizumab reduced it by almost as much at 63% (RR, 0.37; 95% CI, 0.30-0.45).

Benralizumab was slightly less effective than the other two biologics, reducing exacerbation risk by 51% (RR, 0.49; 95% CI, 0.43-0.55). “In patients with eosinophil counts of ≥ 300 cells/mcL, all three biologics had a probability of 1 in improving the exacerbation rate by 20% or more ... in comparison to placebo,” the authors wrote.

Regarding each drug’s effect in improving forced expiratory volume in 1 second (FEV₁), the mean difference in milliliters with dupilumab before and after treatment was 230 (95% CI, 160-300), while for benralizumab, the MD was 150 (95% CI, 100-220) before and after treatment. With mepolizumab, the MD in FEV₁ before and after treatment was also 150. In the same subgroup of patients with eosinophil counts of at least300 cells/mcL, all three biologics again had a probability of 1 in improving FEV₁ by 50 mL or more above the placebo effect. A third endpoint that was analyzed was the potential reduction in asthma control questionnaire (ACQ) scores. With mepolizumab, the MD before and after treatment was –0.65 (95% CI, –0.81 to –0.45); with dupilumab, it was –0.48 (95% CI, –0.83 to –0.14); and with dupilumab, it was –0.32 (95% CI, –0.43 to –0.21).

“Dupilumab was significantly better than benralizumab in improving exacerbations,” the authors noted (RR, 0.66; 95% CI, 0.47-0.94), while mepolizumab was also better than benralizumab (RR, 0.75; 95% CI, 0.60-0.95). On the other hand, both dupilumab and benralizumab led to greater improvements in FEV₁ than mepolizumab, although the effects of dupilumab and benralizumab on ACQ scores were not significantly different for patients whose lower eosinophil counts were between 150 and 299 cells/mcL.

As for safety outcomes, both mepolizumab and benralizumab were associated with a lower risk of serious adverse events, but dupilumab was not different from placebo in terms of overall safety, according to the authors. “The ultimate choice of biologic for each patient would ... depend on multiple factors including cost considerations and timing of administration.

“[However], these results may be helpful to clinicians as they optimize patient care,” they concluded. Limitations to the analysis include the fact that indirect comparisons cannot replace randomized trials that compare the three drugs directly.

It’s estimated that 5%-10% of the 26 million individuals with asthma in the United States have severe disease.

Dr. Akenroye disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Falsely elevated pulse oximeter readings are leading to less oxygen supplementation for people of color, a recent study finds.

The new research suggests that skin color–related differences in pulse oximeter readings are in fact impacting clinical decision-making, lead author Eric R. Gottlieb, MD, of Brigham and Women’s Hospital and Massachusetts Institute of Technology, both in Boston, and colleagues wrote. This suggests that technology needs to updated to improve health equity, they continued, in their paper published in JAMA Internal Medicine.

“It has been known for decades that these readings are affected by various surface pigmentations, including nail polish and skin melanin, which may affect light absorption and scattering,” the investigators wrote. “This increases the risk of hidden hypoxemia [among patients with darker skin], in which patients have falsely elevated SpO₂ readings, usually defined as 92% or greater, with a blood hemoglobin oxygen saturation less than 88%.”

Although published reports on this phenomenon date back to the 1980s, clinical significance has been largely discounted, they said, citing a 2008 paper on the topic, which stated that “oximetry need not have exact accuracy” to determine if a patient needs oxygen supplementation.
 

‘We’re not providing equal care’

Questioning the validity of this statement, Dr. Gottlieb and colleagues conducted a retrospective cohort study involving 3,069 patients admitted to intensive care at the Beth Israel Deaconess Medical Center in Boston between 2008 and 2019, thereby excluding patients treated during the COVID-19 pandemic. The population consisted of four races/ethnicities: White (87%), Black (7%), Hispanic (4%), and Asian (3%).

Aligning with previous studies, multivariable linear regression analyses showed that Asian, Black, and Hispanic patients had significantly higher SpO₂ readings than White patients in relation to hemoglobin oxygen saturation values, suggesting falsely elevated readings.

Further modeling showed that these same patient groups also received lower oxygen delivery rates, which were not explained directly by race/ethnicity, but instead were mediated by the discrepancy between SpO₂ and hemoglobin oxygen saturation values. In other words, physicians were responding consistently to pulse oximetry readings, rather than exhibiting a direct racial/ethnic bias in their clinical decision-making.

“We’re not providing equal care,” Dr. Gottlieb said in an interview. “It’s not that the patients are sicker, or have other socioeconomic explanations for why this happens to them. It’s us. It’s our technology. And that’s something that really has to be fixed.”

The investigators offered a cautionary view of corrective algorithms, as these “have exacerbated disparities and are subject to ethical concerns;” for example, with glomerular filtration rate estimations in Black patients.

Dr. Gottlieb also cautioned against action by individual physicians, who may now be inclined to change how they interpret pulse oximeter readings based on a patient’s race or ethnicity.

“I don’t think that we can expect physicians, every time they see a patient, to be second guessing whether the number basically reflects the truth,” he said.

Instead, Dr. Gottlieb suggested that the burden of change rests upon the shoulders of institutions, including hospitals and device manufacturers, both of which “really need to take the responsibility” for making sure that pulse oximeters are “equitable and have similar performance across races.”

While Dr. Gottlieb said that skin color likely plays the greatest role in measurement discrepancies, he encouraged stakeholders “to think broadly about this, and not just assume that it’s entirely skin color,” noting a small amount of evidence indicating that blood chemistry may also play a role. Still, he predicted that colorimetry – the direct measurement of skin color – will probably be incorporated into pulse oximeters of the future.
 

Black patients 3X more likely to have hidden hypoxia than White patients

Michael Sjoding, MD, of the University of Michigan, Ann Arbor, was one of the first to raise awareness of skin color–related issues with pulse oximeters during the throes of the COVID-19 pandemic. His study, which involved more than 10,000 patients, showed that Black patients were threefold more likely to have hidden hypoxia than White patients.

The present study shows that such discrepancies are indeed clinically significant, Dr. Sjoding said in an interview. And these data are needed, he added, to bring about change.

“What is being asked is potentially a big deal,” Dr. Sjoding said. “Pulse oximeters are everywhere, and it would be a big undertaking to redesign pulse oximeters and purchase new pulse oximeters. You need a compelling body of evidence to do that. I think it’s there now, clearly. So I’m hopeful that we’re going to finally move forward, towards having devices that we are confident work accurately in everyone.”

Why it has taken so long to gather this evidence, however, is a thornier topic, considering race-related discrepancies in pulse oximeter readings were first documented more than 3 decades ago.

“We sort of rediscovered something that had been known and had been described in the past,” Dr. Sjoding said. He explained how he and many of his colleagues had completed pulmonary fellowships, yet none of them knew of these potential issues with pulse oximeters until they began to observe differences in their own patients during the pandemic.

“I’ll give previous generations of researchers the benefit of the doubt,” Dr. Sjoding said, pointing out that techniques in data gathering and analysis have advanced considerably over the years. “The types of studies that were done before were very different than what we did.”

Yet Dr. Sjoding entertained the possibility that other factors may have been at play.

“I think definitely there’s a social commentary on prioritization of research,” he said.

The study was supported by grants from the National Institutes of Health. The investigators and Dr. Sjoding reported no conflicts of interest.

Falsely elevated pulse oximeter readings are leading to less oxygen supplementation for people of color, a recent study finds.

The new research suggests that skin color–related differences in pulse oximeter readings are in fact impacting clinical decision-making, lead author Eric R. Gottlieb, MD, of Brigham and Women’s Hospital and Massachusetts Institute of Technology, both in Boston, and colleagues wrote. This suggests that technology needs to updated to improve health equity, they continued, in their paper published in JAMA Internal Medicine.

“It has been known for decades that these readings are affected by various surface pigmentations, including nail polish and skin melanin, which may affect light absorption and scattering,” the investigators wrote. “This increases the risk of hidden hypoxemia [among patients with darker skin], in which patients have falsely elevated SpO₂ readings, usually defined as 92% or greater, with a blood hemoglobin oxygen saturation less than 88%.”

Although published reports on this phenomenon date back to the 1980s, clinical significance has been largely discounted, they said, citing a 2008 paper on the topic, which stated that “oximetry need not have exact accuracy” to determine if a patient needs oxygen supplementation.
 

‘We’re not providing equal care’

Questioning the validity of this statement, Dr. Gottlieb and colleagues conducted a retrospective cohort study involving 3,069 patients admitted to intensive care at the Beth Israel Deaconess Medical Center in Boston between 2008 and 2019, thereby excluding patients treated during the COVID-19 pandemic. The population consisted of four races/ethnicities: White (87%), Black (7%), Hispanic (4%), and Asian (3%).

Aligning with previous studies, multivariable linear regression analyses showed that Asian, Black, and Hispanic patients had significantly higher SpO₂ readings than White patients in relation to hemoglobin oxygen saturation values, suggesting falsely elevated readings.

Further modeling showed that these same patient groups also received lower oxygen delivery rates, which were not explained directly by race/ethnicity, but instead were mediated by the discrepancy between SpO₂ and hemoglobin oxygen saturation values. In other words, physicians were responding consistently to pulse oximetry readings, rather than exhibiting a direct racial/ethnic bias in their clinical decision-making.

“We’re not providing equal care,” Dr. Gottlieb said in an interview. “It’s not that the patients are sicker, or have other socioeconomic explanations for why this happens to them. It’s us. It’s our technology. And that’s something that really has to be fixed.”

The investigators offered a cautionary view of corrective algorithms, as these “have exacerbated disparities and are subject to ethical concerns;” for example, with glomerular filtration rate estimations in Black patients.

Dr. Gottlieb also cautioned against action by individual physicians, who may now be inclined to change how they interpret pulse oximeter readings based on a patient’s race or ethnicity.

“I don’t think that we can expect physicians, every time they see a patient, to be second guessing whether the number basically reflects the truth,” he said.

Instead, Dr. Gottlieb suggested that the burden of change rests upon the shoulders of institutions, including hospitals and device manufacturers, both of which “really need to take the responsibility” for making sure that pulse oximeters are “equitable and have similar performance across races.”

While Dr. Gottlieb said that skin color likely plays the greatest role in measurement discrepancies, he encouraged stakeholders “to think broadly about this, and not just assume that it’s entirely skin color,” noting a small amount of evidence indicating that blood chemistry may also play a role. Still, he predicted that colorimetry – the direct measurement of skin color – will probably be incorporated into pulse oximeters of the future.
 

Black patients 3X more likely to have hidden hypoxia than White patients

Michael Sjoding, MD, of the University of Michigan, Ann Arbor, was one of the first to raise awareness of skin color–related issues with pulse oximeters during the throes of the COVID-19 pandemic. His study, which involved more than 10,000 patients, showed that Black patients were threefold more likely to have hidden hypoxia than White patients.

The present study shows that such discrepancies are indeed clinically significant, Dr. Sjoding said in an interview. And these data are needed, he added, to bring about change.

“What is being asked is potentially a big deal,” Dr. Sjoding said. “Pulse oximeters are everywhere, and it would be a big undertaking to redesign pulse oximeters and purchase new pulse oximeters. You need a compelling body of evidence to do that. I think it’s there now, clearly. So I’m hopeful that we’re going to finally move forward, towards having devices that we are confident work accurately in everyone.”

Why it has taken so long to gather this evidence, however, is a thornier topic, considering race-related discrepancies in pulse oximeter readings were first documented more than 3 decades ago.

“We sort of rediscovered something that had been known and had been described in the past,” Dr. Sjoding said. He explained how he and many of his colleagues had completed pulmonary fellowships, yet none of them knew of these potential issues with pulse oximeters until they began to observe differences in their own patients during the pandemic.

“I’ll give previous generations of researchers the benefit of the doubt,” Dr. Sjoding said, pointing out that techniques in data gathering and analysis have advanced considerably over the years. “The types of studies that were done before were very different than what we did.”

Yet Dr. Sjoding entertained the possibility that other factors may have been at play.

“I think definitely there’s a social commentary on prioritization of research,” he said.

The study was supported by grants from the National Institutes of Health. The investigators and Dr. Sjoding reported no conflicts of interest.

Falsely elevated pulse oximeter readings are leading to less oxygen supplementation for people of color, a recent study finds.

The new research suggests that skin color–related differences in pulse oximeter readings are in fact impacting clinical decision-making, lead author Eric R. Gottlieb, MD, of Brigham and Women’s Hospital and Massachusetts Institute of Technology, both in Boston, and colleagues wrote. This suggests that technology needs to updated to improve health equity, they continued, in their paper published in JAMA Internal Medicine.

“It has been known for decades that these readings are affected by various surface pigmentations, including nail polish and skin melanin, which may affect light absorption and scattering,” the investigators wrote. “This increases the risk of hidden hypoxemia [among patients with darker skin], in which patients have falsely elevated SpO₂ readings, usually defined as 92% or greater, with a blood hemoglobin oxygen saturation less than 88%.”

Although published reports on this phenomenon date back to the 1980s, clinical significance has been largely discounted, they said, citing a 2008 paper on the topic, which stated that “oximetry need not have exact accuracy” to determine if a patient needs oxygen supplementation.
 

‘We’re not providing equal care’

Questioning the validity of this statement, Dr. Gottlieb and colleagues conducted a retrospective cohort study involving 3,069 patients admitted to intensive care at the Beth Israel Deaconess Medical Center in Boston between 2008 and 2019, thereby excluding patients treated during the COVID-19 pandemic. The population consisted of four races/ethnicities: White (87%), Black (7%), Hispanic (4%), and Asian (3%).

Aligning with previous studies, multivariable linear regression analyses showed that Asian, Black, and Hispanic patients had significantly higher SpO₂ readings than White patients in relation to hemoglobin oxygen saturation values, suggesting falsely elevated readings.

Further modeling showed that these same patient groups also received lower oxygen delivery rates, which were not explained directly by race/ethnicity, but instead were mediated by the discrepancy between SpO₂ and hemoglobin oxygen saturation values. In other words, physicians were responding consistently to pulse oximetry readings, rather than exhibiting a direct racial/ethnic bias in their clinical decision-making.

“We’re not providing equal care,” Dr. Gottlieb said in an interview. “It’s not that the patients are sicker, or have other socioeconomic explanations for why this happens to them. It’s us. It’s our technology. And that’s something that really has to be fixed.”

The investigators offered a cautionary view of corrective algorithms, as these “have exacerbated disparities and are subject to ethical concerns;” for example, with glomerular filtration rate estimations in Black patients.

Dr. Gottlieb also cautioned against action by individual physicians, who may now be inclined to change how they interpret pulse oximeter readings based on a patient’s race or ethnicity.

“I don’t think that we can expect physicians, every time they see a patient, to be second guessing whether the number basically reflects the truth,” he said.

Instead, Dr. Gottlieb suggested that the burden of change rests upon the shoulders of institutions, including hospitals and device manufacturers, both of which “really need to take the responsibility” for making sure that pulse oximeters are “equitable and have similar performance across races.”

While Dr. Gottlieb said that skin color likely plays the greatest role in measurement discrepancies, he encouraged stakeholders “to think broadly about this, and not just assume that it’s entirely skin color,” noting a small amount of evidence indicating that blood chemistry may also play a role. Still, he predicted that colorimetry – the direct measurement of skin color – will probably be incorporated into pulse oximeters of the future.
 

Black patients 3X more likely to have hidden hypoxia than White patients

Michael Sjoding, MD, of the University of Michigan, Ann Arbor, was one of the first to raise awareness of skin color–related issues with pulse oximeters during the throes of the COVID-19 pandemic. His study, which involved more than 10,000 patients, showed that Black patients were threefold more likely to have hidden hypoxia than White patients.

The present study shows that such discrepancies are indeed clinically significant, Dr. Sjoding said in an interview. And these data are needed, he added, to bring about change.

“What is being asked is potentially a big deal,” Dr. Sjoding said. “Pulse oximeters are everywhere, and it would be a big undertaking to redesign pulse oximeters and purchase new pulse oximeters. You need a compelling body of evidence to do that. I think it’s there now, clearly. So I’m hopeful that we’re going to finally move forward, towards having devices that we are confident work accurately in everyone.”

Why it has taken so long to gather this evidence, however, is a thornier topic, considering race-related discrepancies in pulse oximeter readings were first documented more than 3 decades ago.

“We sort of rediscovered something that had been known and had been described in the past,” Dr. Sjoding said. He explained how he and many of his colleagues had completed pulmonary fellowships, yet none of them knew of these potential issues with pulse oximeters until they began to observe differences in their own patients during the pandemic.

“I’ll give previous generations of researchers the benefit of the doubt,” Dr. Sjoding said, pointing out that techniques in data gathering and analysis have advanced considerably over the years. “The types of studies that were done before were very different than what we did.”

Yet Dr. Sjoding entertained the possibility that other factors may have been at play.

“I think definitely there’s a social commentary on prioritization of research,” he said.

The study was supported by grants from the National Institutes of Health. The investigators and Dr. Sjoding reported no conflicts of interest.

Adults with severe asthma (SA) experienced significantly fewer exacerbations on biologic therapies, compared with those who did not use biologics, based on data from more than 2,000 individuals.

The development of biologics to target specific inflammatory pathways “has transformed the management of uncontrolled SA,” but data on the real-world use of biologics in severe asthma patients treated by subspecialists are limited, wrote Reynold A. Panettieri, Jr., MD, of Rutgers, State University of New Jersey, New Brunswick, and colleagues.

In a study published in the Annals of Allergy, Asthma & Immunology, the researchers reviewed data from CHRONICLE, an ongoing, prospective, real-world noninterventional study of adults aged 18 years and older with severe asthma in the United States.

The study population included 2,847 patients enrolled in the CHRONICLE study between February 2018 and February 2021; 68.8% were women, 74.6% were White. The patients ranged in age from 18 to 89 years, with a mean age of 54.2 years.

Biologic use was defined as patients who started or had ongoing use of biologics between 12 months before enrollment and the patient’s most recent data collection. Switches were defined as stopping one biologic and starting another within 6 months; stops were defined as discontinuing a biologic without switching to another within 6 months. A total of 66% of the patients were using biologics at the time of study enrollment. The most common biologic was omalizumab (47%), followed by benralizumab (27%), mepolizumab (26%), and dupilumab (18%).

Overall, 89% of the patients had ongoing biologic use, 16% had biologic switches, and 13% had stops.

Patients who started biologics or switched biologics had significant reductions in asthma exacerbations at 6 months, compared with nonbiologic users of 58% (1.80 vs. 0.76 per patient-year) and 49% (1.47 vs. 0.75 per patient-year), respectively (P < .001 for both). Asthma exacerbations declined by 70% among biologics users for whom data were available for 12 months before and 12 months after starting biologics.

Exacerbations decreased at 6 months after biologic initiation across all subgroups of patients, notably patients with pre-biologic FEV₁ < 80% and patients with FEV₁ ≥ 80% (66% and 53%, respectively); never smokers and current/former smokers (63% and 50%, respectively); and patients with COPD and without COPD (58% and 52%, respectively).

The researchers also found a greater reduction in exacerbations among patients who switched from anti-IgE therapy to anti–IL-5/IL-5R/IL-4R therapy, compared with those who switched among anti–IL-5/IL-5R/IL-4R therapies (58% vs. 46%).

Patients who stopped or switched biologics appeared to have more severe or treatment-refractory disease than those with ongoing biologic use, the researchers noted. The most common reason for stopping or switching was worsening symptoms.

The study findings were limited by several factors, including the focus only on adults in the United States with subspecialist-treated SA, which may limit generalizability to children or other populations, the researchers noted. Other limitations included the variation in clinical decisions and insurance coverage and the inability to conduct longitudinal assessments, they said.

The results demonstrate that starting or switching biologics was consistently associated with fewer exacerbations in severe asthma. However, more research is needed to determine why some patients were not receiving biologics because they were not considered clinically eligible by their subspecialist health care providers, the researchers concluded.

The current study and the CHRONICLE study were supported by AstraZeneca. Lead author Dr. Panettieri disclosed serving on the advisory boards for and receiving grant support from AstraZeneca, Sanofi, Genentech, Regeneron, and Novartis.

Adults with severe asthma (SA) experienced significantly fewer exacerbations on biologic therapies, compared with those who did not use biologics, based on data from more than 2,000 individuals.

The development of biologics to target specific inflammatory pathways “has transformed the management of uncontrolled SA,” but data on the real-world use of biologics in severe asthma patients treated by subspecialists are limited, wrote Reynold A. Panettieri, Jr., MD, of Rutgers, State University of New Jersey, New Brunswick, and colleagues.

In a study published in the Annals of Allergy, Asthma & Immunology, the researchers reviewed data from CHRONICLE, an ongoing, prospective, real-world noninterventional study of adults aged 18 years and older with severe asthma in the United States.

The study population included 2,847 patients enrolled in the CHRONICLE study between February 2018 and February 2021; 68.8% were women, 74.6% were White. The patients ranged in age from 18 to 89 years, with a mean age of 54.2 years.

Biologic use was defined as patients who started or had ongoing use of biologics between 12 months before enrollment and the patient’s most recent data collection. Switches were defined as stopping one biologic and starting another within 6 months; stops were defined as discontinuing a biologic without switching to another within 6 months. A total of 66% of the patients were using biologics at the time of study enrollment. The most common biologic was omalizumab (47%), followed by benralizumab (27%), mepolizumab (26%), and dupilumab (18%).

Overall, 89% of the patients had ongoing biologic use, 16% had biologic switches, and 13% had stops.

Patients who started biologics or switched biologics had significant reductions in asthma exacerbations at 6 months, compared with nonbiologic users of 58% (1.80 vs. 0.76 per patient-year) and 49% (1.47 vs. 0.75 per patient-year), respectively (P < .001 for both). Asthma exacerbations declined by 70% among biologics users for whom data were available for 12 months before and 12 months after starting biologics.

Exacerbations decreased at 6 months after biologic initiation across all subgroups of patients, notably patients with pre-biologic FEV₁ < 80% and patients with FEV₁ ≥ 80% (66% and 53%, respectively); never smokers and current/former smokers (63% and 50%, respectively); and patients with COPD and without COPD (58% and 52%, respectively).

The researchers also found a greater reduction in exacerbations among patients who switched from anti-IgE therapy to anti–IL-5/IL-5R/IL-4R therapy, compared with those who switched among anti–IL-5/IL-5R/IL-4R therapies (58% vs. 46%).

Patients who stopped or switched biologics appeared to have more severe or treatment-refractory disease than those with ongoing biologic use, the researchers noted. The most common reason for stopping or switching was worsening symptoms.

The study findings were limited by several factors, including the focus only on adults in the United States with subspecialist-treated SA, which may limit generalizability to children or other populations, the researchers noted. Other limitations included the variation in clinical decisions and insurance coverage and the inability to conduct longitudinal assessments, they said.

The results demonstrate that starting or switching biologics was consistently associated with fewer exacerbations in severe asthma. However, more research is needed to determine why some patients were not receiving biologics because they were not considered clinically eligible by their subspecialist health care providers, the researchers concluded.

The current study and the CHRONICLE study were supported by AstraZeneca. Lead author Dr. Panettieri disclosed serving on the advisory boards for and receiving grant support from AstraZeneca, Sanofi, Genentech, Regeneron, and Novartis.

Adults with severe asthma (SA) experienced significantly fewer exacerbations on biologic therapies, compared with those who did not use biologics, based on data from more than 2,000 individuals.

The development of biologics to target specific inflammatory pathways “has transformed the management of uncontrolled SA,” but data on the real-world use of biologics in severe asthma patients treated by subspecialists are limited, wrote Reynold A. Panettieri, Jr., MD, of Rutgers, State University of New Jersey, New Brunswick, and colleagues.

In a study published in the Annals of Allergy, Asthma & Immunology, the researchers reviewed data from CHRONICLE, an ongoing, prospective, real-world noninterventional study of adults aged 18 years and older with severe asthma in the United States.

The study population included 2,847 patients enrolled in the CHRONICLE study between February 2018 and February 2021; 68.8% were women, 74.6% were White. The patients ranged in age from 18 to 89 years, with a mean age of 54.2 years.

Biologic use was defined as patients who started or had ongoing use of biologics between 12 months before enrollment and the patient’s most recent data collection. Switches were defined as stopping one biologic and starting another within 6 months; stops were defined as discontinuing a biologic without switching to another within 6 months. A total of 66% of the patients were using biologics at the time of study enrollment. The most common biologic was omalizumab (47%), followed by benralizumab (27%), mepolizumab (26%), and dupilumab (18%).

Overall, 89% of the patients had ongoing biologic use, 16% had biologic switches, and 13% had stops.

Patients who started biologics or switched biologics had significant reductions in asthma exacerbations at 6 months, compared with nonbiologic users of 58% (1.80 vs. 0.76 per patient-year) and 49% (1.47 vs. 0.75 per patient-year), respectively (P < .001 for both). Asthma exacerbations declined by 70% among biologics users for whom data were available for 12 months before and 12 months after starting biologics.

Exacerbations decreased at 6 months after biologic initiation across all subgroups of patients, notably patients with pre-biologic FEV₁ < 80% and patients with FEV₁ ≥ 80% (66% and 53%, respectively); never smokers and current/former smokers (63% and 50%, respectively); and patients with COPD and without COPD (58% and 52%, respectively).

The researchers also found a greater reduction in exacerbations among patients who switched from anti-IgE therapy to anti–IL-5/IL-5R/IL-4R therapy, compared with those who switched among anti–IL-5/IL-5R/IL-4R therapies (58% vs. 46%).

Patients who stopped or switched biologics appeared to have more severe or treatment-refractory disease than those with ongoing biologic use, the researchers noted. The most common reason for stopping or switching was worsening symptoms.

The study findings were limited by several factors, including the focus only on adults in the United States with subspecialist-treated SA, which may limit generalizability to children or other populations, the researchers noted. Other limitations included the variation in clinical decisions and insurance coverage and the inability to conduct longitudinal assessments, they said.

The results demonstrate that starting or switching biologics was consistently associated with fewer exacerbations in severe asthma. However, more research is needed to determine why some patients were not receiving biologics because they were not considered clinically eligible by their subspecialist health care providers, the researchers concluded.

The current study and the CHRONICLE study were supported by AstraZeneca. Lead author Dr. Panettieri disclosed serving on the advisory boards for and receiving grant support from AstraZeneca, Sanofi, Genentech, Regeneron, and Novartis.

Chronic obstructive pulmonary disease (COPD) was among the significant predictors of hospital readmission in older adults with fractures, based on data from nearly 400 individuals.

Fractures in the elderly remain a major health concern, and readmissions are common; however, “The predictive factors for hospital readmission of elderly people with fractures are multifactorial and complex,” Lara Cristina da Cunha Guimarães, MSN, of State School of Public Health Candido Santiago, State Department of Health of Goiás (Brazil), and colleagues wrote.

Previous research suggests that readmissions risk may be greater in patients with preadmission conditions including pulmonary and cardiac disease, history of stroke and other neurological conditions, and other factors associated with aging in general, they said.

In a study published in the journal Injury , the researchers reviewed data from 376 adults aged 60 years and older in a trauma referral hospital in Brazil who had suffered fractures and were hospitalized between Sept. 1, 2016, and Feb. 28, 2017. The primary outcome was readmission up to one year after discharge from the initial hospitalization for fracture.

Approximately half of the patients experienced femur fractures (53.2%), and the most frequent cause was falling from standing height (72.9%). The overall incidence of readmission was 20.7%. A total of 30.5% of readmissions were related to the fracture, and surgical-site infections were the most common cause of fracture-related complications.

More than half (58.3%) of the readmissions were related to clinical complications.

In a multivariate analysis, several clinical factors not related to fractures were independently associated with readmission, including a previous diagnosis of COPD, age between 60 and 69 years, a fracture of the femur, and delirium at the time of the first hospitalization for fracture.

Pneumonia was the most frequent cause of clinical complications, reflecting data from other recent studies, the researchers noted. “Elderly people with COPD are more susceptible to infections, such as pneumonia, which was a cause of frequent readmissions in the population studied. The presence of COPD can contribute to imbalance in the pulmonary microbiome, mucus production and persistent inflammation of the airways, and structural damage, which increases exposure of the pulmonary mucosa to pathogens.” COPD also can be associated with cardiovascular, mental, and musculoskeletal diseases that can further complicate and delay recovery from fractures.

The study findings were limited by the potential for incomplete information in medical records. However, the results indicate a range of causes and conditions associated with hospital readmission after fractures in older adults, they said. Recognizing these factors can guide plans for transitions from hospital to home care to reduce complications and readmissions.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Chronic obstructive pulmonary disease (COPD) was among the significant predictors of hospital readmission in older adults with fractures, based on data from nearly 400 individuals.

Fractures in the elderly remain a major health concern, and readmissions are common; however, “The predictive factors for hospital readmission of elderly people with fractures are multifactorial and complex,” Lara Cristina da Cunha Guimarães, MSN, of State School of Public Health Candido Santiago, State Department of Health of Goiás (Brazil), and colleagues wrote.

Previous research suggests that readmissions risk may be greater in patients with preadmission conditions including pulmonary and cardiac disease, history of stroke and other neurological conditions, and other factors associated with aging in general, they said.

In a study published in the journal Injury , the researchers reviewed data from 376 adults aged 60 years and older in a trauma referral hospital in Brazil who had suffered fractures and were hospitalized between Sept. 1, 2016, and Feb. 28, 2017. The primary outcome was readmission up to one year after discharge from the initial hospitalization for fracture.

Approximately half of the patients experienced femur fractures (53.2%), and the most frequent cause was falling from standing height (72.9%). The overall incidence of readmission was 20.7%. A total of 30.5% of readmissions were related to the fracture, and surgical-site infections were the most common cause of fracture-related complications.

More than half (58.3%) of the readmissions were related to clinical complications.

In a multivariate analysis, several clinical factors not related to fractures were independently associated with readmission, including a previous diagnosis of COPD, age between 60 and 69 years, a fracture of the femur, and delirium at the time of the first hospitalization for fracture.

Pneumonia was the most frequent cause of clinical complications, reflecting data from other recent studies, the researchers noted. “Elderly people with COPD are more susceptible to infections, such as pneumonia, which was a cause of frequent readmissions in the population studied. The presence of COPD can contribute to imbalance in the pulmonary microbiome, mucus production and persistent inflammation of the airways, and structural damage, which increases exposure of the pulmonary mucosa to pathogens.” COPD also can be associated with cardiovascular, mental, and musculoskeletal diseases that can further complicate and delay recovery from fractures.

The study findings were limited by the potential for incomplete information in medical records. However, the results indicate a range of causes and conditions associated with hospital readmission after fractures in older adults, they said. Recognizing these factors can guide plans for transitions from hospital to home care to reduce complications and readmissions.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Chronic obstructive pulmonary disease (COPD) was among the significant predictors of hospital readmission in older adults with fractures, based on data from nearly 400 individuals.

Fractures in the elderly remain a major health concern, and readmissions are common; however, “The predictive factors for hospital readmission of elderly people with fractures are multifactorial and complex,” Lara Cristina da Cunha Guimarães, MSN, of State School of Public Health Candido Santiago, State Department of Health of Goiás (Brazil), and colleagues wrote.

Previous research suggests that readmissions risk may be greater in patients with preadmission conditions including pulmonary and cardiac disease, history of stroke and other neurological conditions, and other factors associated with aging in general, they said.

In a study published in the journal Injury , the researchers reviewed data from 376 adults aged 60 years and older in a trauma referral hospital in Brazil who had suffered fractures and were hospitalized between Sept. 1, 2016, and Feb. 28, 2017. The primary outcome was readmission up to one year after discharge from the initial hospitalization for fracture.

Approximately half of the patients experienced femur fractures (53.2%), and the most frequent cause was falling from standing height (72.9%). The overall incidence of readmission was 20.7%. A total of 30.5% of readmissions were related to the fracture, and surgical-site infections were the most common cause of fracture-related complications.

More than half (58.3%) of the readmissions were related to clinical complications.

In a multivariate analysis, several clinical factors not related to fractures were independently associated with readmission, including a previous diagnosis of COPD, age between 60 and 69 years, a fracture of the femur, and delirium at the time of the first hospitalization for fracture.

Pneumonia was the most frequent cause of clinical complications, reflecting data from other recent studies, the researchers noted. “Elderly people with COPD are more susceptible to infections, such as pneumonia, which was a cause of frequent readmissions in the population studied. The presence of COPD can contribute to imbalance in the pulmonary microbiome, mucus production and persistent inflammation of the airways, and structural damage, which increases exposure of the pulmonary mucosa to pathogens.” COPD also can be associated with cardiovascular, mental, and musculoskeletal diseases that can further complicate and delay recovery from fractures.

The study findings were limited by the potential for incomplete information in medical records. However, the results indicate a range of causes and conditions associated with hospital readmission after fractures in older adults, they said. Recognizing these factors can guide plans for transitions from hospital to home care to reduce complications and readmissions.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Young children with allergies may be more likely to develop attention-deficit/hyperactivity disorder and autism spectrum disorder (ASD) by the time they’re 18, according to a large retrospective study.

“Our study provides strong evidence for the association between allergic disorders in early childhood and the development of ADHD,” Shay Nemet, MD, of the Kaplan Medical Center, Rehovot, Israel, and colleagues write in Pediatric Allergy and Immunology. “The risk of those children to develop ASD was less significant.”

The researchers analyzed data from 117,022 consecutive children diagnosed with at least one allergic disorder – asthma, conjunctivitis, rhinitis, and drug, food, or skin allergy – and 116,968 children without allergies in the Clalit Health Services pediatric database. The children had been treated from 2000 to 2018; the mean follow-up period was 11 years.

The children who were diagnosed with one or more allergies (mean age, 4.5 years) were significantly more likely to develop ADHD (odds ratio, 2.45; 95% confidence interval, 2.39-2.51), ASD (OR, 1.17; 95% CI, 1.08-1.27), or both ADHD and ASD (OR, 1.56; 95% CI, 1.35-1.79) than were the control children who did not have allergies.

Children diagnosed with rhinitis (OR, 3.96; 95% CI, 3.80-4.12) and conjunctivitis (OR, 3.63; 95% CI, 3.53-3.74) were the most likely to develop ADHD.
 

Allergy correlation with ADHD and ASD

Cy B. Nadler, PhD, a clinical psychologist and the director of Autism Services at Children’s Mercy Kansas City, Missouri, told this news organization that children and adults with neurodevelopmental differences are also more likely to have other health problems.

“Clinicians practicing in subspecialties such as allergy and immunology may have opportunities to help psychologists identify developmental and behavioral concerns early in childhood,” he added.

“Studies like this can’t be accomplished without large health care databases, but this approach has drawbacks, too,” Dr. Nadler said in an email. “Without more information about these patients’ co-occurring medical and behavioral conditions, we are almost certainly missing important contributors to the observed associations.”

Dr. Nadler, who was not involved in the study, noted that in the multivariable analysis that controlled for age at study entry, gender, and number of annual visits, the link between allergy and ASD diagnosis was not significant.

“It is important to remember not to interpret these study results as causal,” he added.

Desha M. Jordan, MD, FAAP, an assistant professor of pediatrics at UPMC Children’s Hospital of Pittsburgh, called the study “an interesting new area that has been speculated about for some time” and “one of the first I have seen with statistically significant correlations found between ADHD, ASD, and allergic conditions.”
 

More questions for future studies

Health care providers need to understand the potential sequelae of allergic conditions so that they can manage their patients appropriately, she advised.

Although symptoms and diagnoses were confirmed for all patients, the study’s retrospective design and the possibility of recall bias were limitations, said Dr. Jordan in an email. She also was not involved in the study.

“For example, the family of a child diagnosed with ADHD or ASD may have been more mindful of anything out of the norm in that child’s past, while the family of a child without these conditions may not have recalled allergic symptoms as important,” she explained.

Another question that arises is whether some patients were treated and managed well while others were not and whether this disparity in care affected the development or severity of ADHD or ASD, she added.

“Is a patient with a well-controlled allergic condition less likely to develop ADHD or ASD than a patient with an uncontrolled allergic condition? Does a well-controlled patient ever return to the same probability of getting ADHD or ASD as a nonallergic patient?”

“While this study expands our understanding of these conditions and their interrelationships, it also brings up many additional questions and opens a new segment of research,” Dr. Jordan said. “More studies in this area are necessary to confirm the findings of this paper.”

The study was partially funded by the Israel Ambulatory Pediatric Association. The authors, Dr. Nadler, and Dr. Jordan report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Young children with allergies may be more likely to develop attention-deficit/hyperactivity disorder and autism spectrum disorder (ASD) by the time they’re 18, according to a large retrospective study.

“Our study provides strong evidence for the association between allergic disorders in early childhood and the development of ADHD,” Shay Nemet, MD, of the Kaplan Medical Center, Rehovot, Israel, and colleagues write in Pediatric Allergy and Immunology. “The risk of those children to develop ASD was less significant.”

The researchers analyzed data from 117,022 consecutive children diagnosed with at least one allergic disorder – asthma, conjunctivitis, rhinitis, and drug, food, or skin allergy – and 116,968 children without allergies in the Clalit Health Services pediatric database. The children had been treated from 2000 to 2018; the mean follow-up period was 11 years.

The children who were diagnosed with one or more allergies (mean age, 4.5 years) were significantly more likely to develop ADHD (odds ratio, 2.45; 95% confidence interval, 2.39-2.51), ASD (OR, 1.17; 95% CI, 1.08-1.27), or both ADHD and ASD (OR, 1.56; 95% CI, 1.35-1.79) than were the control children who did not have allergies.

Children diagnosed with rhinitis (OR, 3.96; 95% CI, 3.80-4.12) and conjunctivitis (OR, 3.63; 95% CI, 3.53-3.74) were the most likely to develop ADHD.
 

Allergy correlation with ADHD and ASD

Cy B. Nadler, PhD, a clinical psychologist and the director of Autism Services at Children’s Mercy Kansas City, Missouri, told this news organization that children and adults with neurodevelopmental differences are also more likely to have other health problems.

“Clinicians practicing in subspecialties such as allergy and immunology may have opportunities to help psychologists identify developmental and behavioral concerns early in childhood,” he added.

“Studies like this can’t be accomplished without large health care databases, but this approach has drawbacks, too,” Dr. Nadler said in an email. “Without more information about these patients’ co-occurring medical and behavioral conditions, we are almost certainly missing important contributors to the observed associations.”

Dr. Nadler, who was not involved in the study, noted that in the multivariable analysis that controlled for age at study entry, gender, and number of annual visits, the link between allergy and ASD diagnosis was not significant.

“It is important to remember not to interpret these study results as causal,” he added.

Desha M. Jordan, MD, FAAP, an assistant professor of pediatrics at UPMC Children’s Hospital of Pittsburgh, called the study “an interesting new area that has been speculated about for some time” and “one of the first I have seen with statistically significant correlations found between ADHD, ASD, and allergic conditions.”
 

More questions for future studies

Health care providers need to understand the potential sequelae of allergic conditions so that they can manage their patients appropriately, she advised.

Although symptoms and diagnoses were confirmed for all patients, the study’s retrospective design and the possibility of recall bias were limitations, said Dr. Jordan in an email. She also was not involved in the study.

“For example, the family of a child diagnosed with ADHD or ASD may have been more mindful of anything out of the norm in that child’s past, while the family of a child without these conditions may not have recalled allergic symptoms as important,” she explained.

Another question that arises is whether some patients were treated and managed well while others were not and whether this disparity in care affected the development or severity of ADHD or ASD, she added.

“Is a patient with a well-controlled allergic condition less likely to develop ADHD or ASD than a patient with an uncontrolled allergic condition? Does a well-controlled patient ever return to the same probability of getting ADHD or ASD as a nonallergic patient?”

“While this study expands our understanding of these conditions and their interrelationships, it also brings up many additional questions and opens a new segment of research,” Dr. Jordan said. “More studies in this area are necessary to confirm the findings of this paper.”

The study was partially funded by the Israel Ambulatory Pediatric Association. The authors, Dr. Nadler, and Dr. Jordan report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Young children with allergies may be more likely to develop attention-deficit/hyperactivity disorder and autism spectrum disorder (ASD) by the time they’re 18, according to a large retrospective study.

“Our study provides strong evidence for the association between allergic disorders in early childhood and the development of ADHD,” Shay Nemet, MD, of the Kaplan Medical Center, Rehovot, Israel, and colleagues write in Pediatric Allergy and Immunology. “The risk of those children to develop ASD was less significant.”

The researchers analyzed data from 117,022 consecutive children diagnosed with at least one allergic disorder – asthma, conjunctivitis, rhinitis, and drug, food, or skin allergy – and 116,968 children without allergies in the Clalit Health Services pediatric database. The children had been treated from 2000 to 2018; the mean follow-up period was 11 years.

The children who were diagnosed with one or more allergies (mean age, 4.5 years) were significantly more likely to develop ADHD (odds ratio, 2.45; 95% confidence interval, 2.39-2.51), ASD (OR, 1.17; 95% CI, 1.08-1.27), or both ADHD and ASD (OR, 1.56; 95% CI, 1.35-1.79) than were the control children who did not have allergies.

Children diagnosed with rhinitis (OR, 3.96; 95% CI, 3.80-4.12) and conjunctivitis (OR, 3.63; 95% CI, 3.53-3.74) were the most likely to develop ADHD.
 

Allergy correlation with ADHD and ASD

Cy B. Nadler, PhD, a clinical psychologist and the director of Autism Services at Children’s Mercy Kansas City, Missouri, told this news organization that children and adults with neurodevelopmental differences are also more likely to have other health problems.

“Clinicians practicing in subspecialties such as allergy and immunology may have opportunities to help psychologists identify developmental and behavioral concerns early in childhood,” he added.

“Studies like this can’t be accomplished without large health care databases, but this approach has drawbacks, too,” Dr. Nadler said in an email. “Without more information about these patients’ co-occurring medical and behavioral conditions, we are almost certainly missing important contributors to the observed associations.”

Dr. Nadler, who was not involved in the study, noted that in the multivariable analysis that controlled for age at study entry, gender, and number of annual visits, the link between allergy and ASD diagnosis was not significant.

“It is important to remember not to interpret these study results as causal,” he added.

Desha M. Jordan, MD, FAAP, an assistant professor of pediatrics at UPMC Children’s Hospital of Pittsburgh, called the study “an interesting new area that has been speculated about for some time” and “one of the first I have seen with statistically significant correlations found between ADHD, ASD, and allergic conditions.”
 

More questions for future studies

Health care providers need to understand the potential sequelae of allergic conditions so that they can manage their patients appropriately, she advised.

Although symptoms and diagnoses were confirmed for all patients, the study’s retrospective design and the possibility of recall bias were limitations, said Dr. Jordan in an email. She also was not involved in the study.

“For example, the family of a child diagnosed with ADHD or ASD may have been more mindful of anything out of the norm in that child’s past, while the family of a child without these conditions may not have recalled allergic symptoms as important,” she explained.

Another question that arises is whether some patients were treated and managed well while others were not and whether this disparity in care affected the development or severity of ADHD or ASD, she added.

“Is a patient with a well-controlled allergic condition less likely to develop ADHD or ASD than a patient with an uncontrolled allergic condition? Does a well-controlled patient ever return to the same probability of getting ADHD or ASD as a nonallergic patient?”

“While this study expands our understanding of these conditions and their interrelationships, it also brings up many additional questions and opens a new segment of research,” Dr. Jordan said. “More studies in this area are necessary to confirm the findings of this paper.”

The study was partially funded by the Israel Ambulatory Pediatric Association. The authors, Dr. Nadler, and Dr. Jordan report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In an online statement the U.S. Centers for Disease Control and Prevention announced its decision to recommend higher-dose and adjuvanted influenza vaccines for people aged 65 years or older. Fluzone High-Dose Quadrivalent, Flublok Quadrivalent, and Fluad Quadrivalent flu vaccines are among those specified in the release.

The organization says that these higher-dose vaccines may be more effective for the aging population, who often have difficulty mounting a strong enough immune response to protect themselves against the flu virus. People older than 65 years struggle the most during flu season and have the highest proportion of hospitalizations and deaths from flu, according to the release.

But the CDC believes that higher-dose vaccines have the potential to better protect against that danger. One study, from The New England Journal of Medicine, reported that high-dose/adjuvanted vaccines prevented flu in older patients 24% better than did lower-dose/nonadjuvanted vaccines.

These types of vaccines work by creating a larger immune response than a standard vaccine dose. In particular, adjuvanted vaccines contain an extra ingredient within them that helps the immune system produce a stronger reaction to the vaccine. These may be things like aluminum salts, which signal the body to respond faster. Higher-dose vaccines similarly promote a stronger immune response by having more particles of the target virus in their mixture. In theory, this means the body will create an enhanced response to the vaccine. For example, a higher-dose vaccine may quadruple the amount of antigens, compared with the standard dose.

The hope is that this recommendation may increase vaccine use across the board, says José Romero, MD, the director of the CDC’s National Center for Immunization and Respiratory Diseases. As quoted in the CDC announcement, Dr. Romero said that this may help reduce racial inequities in access to flu vaccines. A 2019 meta-analysis concluded that Black and Hispanic people are around 30%-40% less likely to get the flu vaccine. So increasing the access to this medication “could help reduce health disparities by making these vaccines more available to racial and ethnic minority groups,” said Dr. Romero.

The decision, spearheaded by CDC Director Rochelle Walensky, MD, follows recommendations from the Advisory Committee on Immunization Practices, which presented on this topic during a June 22 meeting. It is now part of official CDC policy and will continue to be developed as the 2022-2023 flu season approaches.

In addition, the organization says they’ll reveal more details for their plan later this summer, in their Morbidity and Mortality Weekly Report (MMWR). For now, seniors should know that they should try to get the recommended high-dose vaccines, but if they can’t, then a standard dose of whatever their provider has on hand will do.

At this point, there is still no specific vaccine recommendation for people aged under 65 years. The CDC historically avoids specifying one type of vaccine over another and says each should still be effective in younger patients.

A version of this article first appeared on Medscape.com.

In an online statement the U.S. Centers for Disease Control and Prevention announced its decision to recommend higher-dose and adjuvanted influenza vaccines for people aged 65 years or older. Fluzone High-Dose Quadrivalent, Flublok Quadrivalent, and Fluad Quadrivalent flu vaccines are among those specified in the release.

The organization says that these higher-dose vaccines may be more effective for the aging population, who often have difficulty mounting a strong enough immune response to protect themselves against the flu virus. People older than 65 years struggle the most during flu season and have the highest proportion of hospitalizations and deaths from flu, according to the release.

But the CDC believes that higher-dose vaccines have the potential to better protect against that danger. One study, from The New England Journal of Medicine, reported that high-dose/adjuvanted vaccines prevented flu in older patients 24% better than did lower-dose/nonadjuvanted vaccines.

These types of vaccines work by creating a larger immune response than a standard vaccine dose. In particular, adjuvanted vaccines contain an extra ingredient within them that helps the immune system produce a stronger reaction to the vaccine. These may be things like aluminum salts, which signal the body to respond faster. Higher-dose vaccines similarly promote a stronger immune response by having more particles of the target virus in their mixture. In theory, this means the body will create an enhanced response to the vaccine. For example, a higher-dose vaccine may quadruple the amount of antigens, compared with the standard dose.

The hope is that this recommendation may increase vaccine use across the board, says José Romero, MD, the director of the CDC’s National Center for Immunization and Respiratory Diseases. As quoted in the CDC announcement, Dr. Romero said that this may help reduce racial inequities in access to flu vaccines. A 2019 meta-analysis concluded that Black and Hispanic people are around 30%-40% less likely to get the flu vaccine. So increasing the access to this medication “could help reduce health disparities by making these vaccines more available to racial and ethnic minority groups,” said Dr. Romero.

The decision, spearheaded by CDC Director Rochelle Walensky, MD, follows recommendations from the Advisory Committee on Immunization Practices, which presented on this topic during a June 22 meeting. It is now part of official CDC policy and will continue to be developed as the 2022-2023 flu season approaches.

In addition, the organization says they’ll reveal more details for their plan later this summer, in their Morbidity and Mortality Weekly Report (MMWR). For now, seniors should know that they should try to get the recommended high-dose vaccines, but if they can’t, then a standard dose of whatever their provider has on hand will do.

At this point, there is still no specific vaccine recommendation for people aged under 65 years. The CDC historically avoids specifying one type of vaccine over another and says each should still be effective in younger patients.

A version of this article first appeared on Medscape.com.

In an online statement the U.S. Centers for Disease Control and Prevention announced its decision to recommend higher-dose and adjuvanted influenza vaccines for people aged 65 years or older. Fluzone High-Dose Quadrivalent, Flublok Quadrivalent, and Fluad Quadrivalent flu vaccines are among those specified in the release.

The organization says that these higher-dose vaccines may be more effective for the aging population, who often have difficulty mounting a strong enough immune response to protect themselves against the flu virus. People older than 65 years struggle the most during flu season and have the highest proportion of hospitalizations and deaths from flu, according to the release.

But the CDC believes that higher-dose vaccines have the potential to better protect against that danger. One study, from The New England Journal of Medicine, reported that high-dose/adjuvanted vaccines prevented flu in older patients 24% better than did lower-dose/nonadjuvanted vaccines.

These types of vaccines work by creating a larger immune response than a standard vaccine dose. In particular, adjuvanted vaccines contain an extra ingredient within them that helps the immune system produce a stronger reaction to the vaccine. These may be things like aluminum salts, which signal the body to respond faster. Higher-dose vaccines similarly promote a stronger immune response by having more particles of the target virus in their mixture. In theory, this means the body will create an enhanced response to the vaccine. For example, a higher-dose vaccine may quadruple the amount of antigens, compared with the standard dose.

The hope is that this recommendation may increase vaccine use across the board, says José Romero, MD, the director of the CDC’s National Center for Immunization and Respiratory Diseases. As quoted in the CDC announcement, Dr. Romero said that this may help reduce racial inequities in access to flu vaccines. A 2019 meta-analysis concluded that Black and Hispanic people are around 30%-40% less likely to get the flu vaccine. So increasing the access to this medication “could help reduce health disparities by making these vaccines more available to racial and ethnic minority groups,” said Dr. Romero.

The decision, spearheaded by CDC Director Rochelle Walensky, MD, follows recommendations from the Advisory Committee on Immunization Practices, which presented on this topic during a June 22 meeting. It is now part of official CDC policy and will continue to be developed as the 2022-2023 flu season approaches.

In addition, the organization says they’ll reveal more details for their plan later this summer, in their Morbidity and Mortality Weekly Report (MMWR). For now, seniors should know that they should try to get the recommended high-dose vaccines, but if they can’t, then a standard dose of whatever their provider has on hand will do.

At this point, there is still no specific vaccine recommendation for people aged under 65 years. The CDC historically avoids specifying one type of vaccine over another and says each should still be effective in younger patients.

A version of this article first appeared on Medscape.com.

Air pollution levels mediated the impact of temperature on oxygen saturation in adults with chronic obstructive pulmonary disease (COPD) based on data from 117 individuals.

COPD is attributed to environmental factors including air pollution, and air pollution has been linked to increased risk of hospitalization and mortality because of acute COPD exacerbation, wrote Huan Minh Tran, PhD, of Taipei (Taiwan) Medical University and colleagues. However, the effects of air pollution on climate-associated health outcomes in COPD have not been explored, they said.

In a study published in Science of The Total Environment the researchers identified 117 adult COPD patients at a single center in Taiwan. They measured lung function, 6-minute walking distance, oxygen desaturation, white blood cell count, and percent emphysema (defined as low attenuation area [LAA]) and linked them to 0- to 1-year, 0- to 3-year, and 0- to 5-year lags in exposures to relative humidity (RH), temperature, and air pollution. The mean age of the participants was 72.9 years; 93% were men.

Pollution was defined in terms of fine particulate matter (PM2.5).

Overall, an increase in RH by 1% was associated with increases in forced expiratory volume in 1 second (FEV₁), eosinophils, and lymphocytes.

A 1% increase in RH also was associated with a decrease in the total-lobe LAA.

As for temperature, an increase of 1° C was associated with decreased oxygen desaturation and with decreases in right-, left-, and upper-lobe LAA values.

When the researchers examined the impact of pollution, they found that a 1 mcg/m³ increase in PM2.5 was associated with a decrease in the FEV₁ as well as with an increase in oxygen desaturation. A 1 mcg/m³ increase in PM10 and PM2.5 was associated with increases in the total-, right-, left, and upper-lobe LAA; increases in lower-lobe LAA were associated with an increase in PM2.5 only.

“This is reasonable because PM2.5 can travel and deposit in distal parts of the lung, while PM10 is preferably deposited in the larger airways of the upper lung regions,” the researchers wrote in their discussion.

A one part per billion increase in nitrogen dioxide (NO₂) was associated with decreased FEV₁ and increased upper-lobe LAA.

“We observed that NO₂ fully mediated the association between RH and FEV₁, while PM2.5 fully mediated associations of temperature with oxygen saturation and emphysema severity in COPD patients,” the researchers added.

The study findings were limited by several factors including the relatively small and homogeneous male, Taiwanese population, which may limit generalizability, the researchers noted. Other limitations included the lack of control for factors such as body mass index, occupational exposure, comorbidities, medication use, and indoor air pollution, they said.

However, the results suggest that air pollution could have an effect on the established associations between climate and adverse health outcomes in COPD, and more research is needed. Climate change–related air pollution is an important public health issue, especially with regards to respiratory disease,” they concluded.

The study was supported by the Ministry of Science and Technology of Taiwan. The researchers had no financial conflicts to disclose.

Air pollution levels mediated the impact of temperature on oxygen saturation in adults with chronic obstructive pulmonary disease (COPD) based on data from 117 individuals.

COPD is attributed to environmental factors including air pollution, and air pollution has been linked to increased risk of hospitalization and mortality because of acute COPD exacerbation, wrote Huan Minh Tran, PhD, of Taipei (Taiwan) Medical University and colleagues. However, the effects of air pollution on climate-associated health outcomes in COPD have not been explored, they said.

In a study published in Science of The Total Environment the researchers identified 117 adult COPD patients at a single center in Taiwan. They measured lung function, 6-minute walking distance, oxygen desaturation, white blood cell count, and percent emphysema (defined as low attenuation area [LAA]) and linked them to 0- to 1-year, 0- to 3-year, and 0- to 5-year lags in exposures to relative humidity (RH), temperature, and air pollution. The mean age of the participants was 72.9 years; 93% were men.

Pollution was defined in terms of fine particulate matter (PM2.5).

Overall, an increase in RH by 1% was associated with increases in forced expiratory volume in 1 second (FEV₁), eosinophils, and lymphocytes.

A 1% increase in RH also was associated with a decrease in the total-lobe LAA.

As for temperature, an increase of 1° C was associated with decreased oxygen desaturation and with decreases in right-, left-, and upper-lobe LAA values.

When the researchers examined the impact of pollution, they found that a 1 mcg/m³ increase in PM2.5 was associated with a decrease in the FEV₁ as well as with an increase in oxygen desaturation. A 1 mcg/m³ increase in PM10 and PM2.5 was associated with increases in the total-, right-, left, and upper-lobe LAA; increases in lower-lobe LAA were associated with an increase in PM2.5 only.

“This is reasonable because PM2.5 can travel and deposit in distal parts of the lung, while PM10 is preferably deposited in the larger airways of the upper lung regions,” the researchers wrote in their discussion.

A one part per billion increase in nitrogen dioxide (NO₂) was associated with decreased FEV₁ and increased upper-lobe LAA.

“We observed that NO₂ fully mediated the association between RH and FEV₁, while PM2.5 fully mediated associations of temperature with oxygen saturation and emphysema severity in COPD patients,” the researchers added.

The study findings were limited by several factors including the relatively small and homogeneous male, Taiwanese population, which may limit generalizability, the researchers noted. Other limitations included the lack of control for factors such as body mass index, occupational exposure, comorbidities, medication use, and indoor air pollution, they said.

However, the results suggest that air pollution could have an effect on the established associations between climate and adverse health outcomes in COPD, and more research is needed. Climate change–related air pollution is an important public health issue, especially with regards to respiratory disease,” they concluded.

The study was supported by the Ministry of Science and Technology of Taiwan. The researchers had no financial conflicts to disclose.

Air pollution levels mediated the impact of temperature on oxygen saturation in adults with chronic obstructive pulmonary disease (COPD) based on data from 117 individuals.

COPD is attributed to environmental factors including air pollution, and air pollution has been linked to increased risk of hospitalization and mortality because of acute COPD exacerbation, wrote Huan Minh Tran, PhD, of Taipei (Taiwan) Medical University and colleagues. However, the effects of air pollution on climate-associated health outcomes in COPD have not been explored, they said.

In a study published in Science of The Total Environment the researchers identified 117 adult COPD patients at a single center in Taiwan. They measured lung function, 6-minute walking distance, oxygen desaturation, white blood cell count, and percent emphysema (defined as low attenuation area [LAA]) and linked them to 0- to 1-year, 0- to 3-year, and 0- to 5-year lags in exposures to relative humidity (RH), temperature, and air pollution. The mean age of the participants was 72.9 years; 93% were men.

Pollution was defined in terms of fine particulate matter (PM2.5).

Overall, an increase in RH by 1% was associated with increases in forced expiratory volume in 1 second (FEV₁), eosinophils, and lymphocytes.

A 1% increase in RH also was associated with a decrease in the total-lobe LAA.

As for temperature, an increase of 1° C was associated with decreased oxygen desaturation and with decreases in right-, left-, and upper-lobe LAA values.

When the researchers examined the impact of pollution, they found that a 1 mcg/m³ increase in PM2.5 was associated with a decrease in the FEV₁ as well as with an increase in oxygen desaturation. A 1 mcg/m³ increase in PM10 and PM2.5 was associated with increases in the total-, right-, left, and upper-lobe LAA; increases in lower-lobe LAA were associated with an increase in PM2.5 only.

“This is reasonable because PM2.5 can travel and deposit in distal parts of the lung, while PM10 is preferably deposited in the larger airways of the upper lung regions,” the researchers wrote in their discussion.

A one part per billion increase in nitrogen dioxide (NO₂) was associated with decreased FEV₁ and increased upper-lobe LAA.

“We observed that NO₂ fully mediated the association between RH and FEV₁, while PM2.5 fully mediated associations of temperature with oxygen saturation and emphysema severity in COPD patients,” the researchers added.

The study findings were limited by several factors including the relatively small and homogeneous male, Taiwanese population, which may limit generalizability, the researchers noted. Other limitations included the lack of control for factors such as body mass index, occupational exposure, comorbidities, medication use, and indoor air pollution, they said.

However, the results suggest that air pollution could have an effect on the established associations between climate and adverse health outcomes in COPD, and more research is needed. Climate change–related air pollution is an important public health issue, especially with regards to respiratory disease,” they concluded.

The study was supported by the Ministry of Science and Technology of Taiwan. The researchers had no financial conflicts to disclose.