Pulmonology

This study was published on Medrxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• in analyses of more than 100,000 women that used Mendelian randomization (MR) as a tool to reduce residual confounding.
• The MR analyses showed no significant association between ANM and breast cancer, endometrial cancer, ovarian cancer, coronary heart disease, ischemic stroke, and Alzheimer’s disease.
• The clear lack of a causal effect of ANM on the outcomes of coronary heart disease and ischemic stroke in the MR analyses despite a strong inverse association seen in the observational data of this study (without MR) suggests residual confounding plays a substantial role in driving the observed outcomes.

Why this matters

• The authors said that, to their knowledge, this is the first study that has shown a causal association between older ANM and higher risk of postmenopausal lung cancer.
• This finding was directionally opposite to the significant protective effect of increased ANM documented in an observational analysis of roughly the same data as well as prior reports that did not use MR. This “notable inconsistency” suggests very substantial residual confounding without MR that could be driven by factors such as smoking, diet, and exercise.
• If these results are replicated in additional datasets, it would highlight a need for randomized, controlled trials of antiestrogen therapies in postmenopausal women for the prevention or treatment of lung cancer.

Study design

• The study included data from 106,853 postmenopausal women enrolled in the Women’s Health Initiative (WHI) and 95,464 women who were 37-73 years old included in the UK Biobank (UKB). Analyses for each outcome also included data from smaller numbers of women obtained from several additional datasets.
• The MR analysis used up to 55 single-nucleotide polymorphisms previously discovered through a genome-wide association study of about 70,000 women of European ancestry and independent of all datasets analyzed in the current study. The authors included all single-nucleotide polymorphisms with a consistent direction of effect on ANM.
• The MR analysis for lung cancer included 113,371 women from the two primary datasets and an additional 3012 women from six additional datasets.
• The MR analysis for bone fracture involved 113,239 women from the WHI and UKB only. The MR analysis for osteoporosis involved 137,080 women from the WHI, UKB, and one additional external dataset.

Key results

• Results from a meta-analysis of the MR results using data from the WHI, UKB, and the additional datasets showed ANM was causally associated with an increased risk of lung cancer by an odds ratio of 1.35 for each 5-year increase in ANM. In contrast, the adjusted observational analysis of data just from the WHI and UKB showed a significant 11% relative risk reduction in the incidence of lung cancer for each 5-year increase in ANM.
• The MR results also showed causally protective effects for fracture, with a 24% relative risk reduction, and for osteoporosis, with a 19% relative risk reduction for each 5-year increase in ANM.
• The MR analyses showed no significant association between AMN and outcome for breast cancer, endometrial cancer, ovarian cancer, coronary heart disease, ischemic stroke, and Alzheimer’s disease.

Limitations

The main limitation of the MR study was the potential for inadequate power for assessing some outcomes despite the large overall size of the study cohort. Lack of adequate power may be responsible for some of the nonsignificant associations seen in the study, such as for breast and endometrial cancers, where substantial prior evidence has implicated increased risk through the effects of prolonged exposure to endogenous or exogenous estrogens.

The healthy cohort effect in the UKB is a known weakness of this dataset that may have limited the number of cases and generalizability of findings.

Osteoporosis and Alzheimer’s disease were self-reported.

The study only included participants of European ancestry because most subjects in most of the cohorts examined were White women and the applied MR instruments were found by genome-wide association studies run predominantly in White women. The authors said the causal effects of ANM need study in more diverse populations.
 

Disclosures

• The study received no commercial funding.
• None of the authors had disclosures.

This is a summary of a preprint research study, “Genetic evidence for causal relationships between age at natural menopause and the risk of aging-associated adverse health outcomes,” written by authors primarily based at Stanford University School of Medicine i

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

This study was published on Medrxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• in analyses of more than 100,000 women that used Mendelian randomization (MR) as a tool to reduce residual confounding.
• The MR analyses showed no significant association between ANM and breast cancer, endometrial cancer, ovarian cancer, coronary heart disease, ischemic stroke, and Alzheimer’s disease.
• The clear lack of a causal effect of ANM on the outcomes of coronary heart disease and ischemic stroke in the MR analyses despite a strong inverse association seen in the observational data of this study (without MR) suggests residual confounding plays a substantial role in driving the observed outcomes.

Why this matters

• The authors said that, to their knowledge, this is the first study that has shown a causal association between older ANM and higher risk of postmenopausal lung cancer.
• This finding was directionally opposite to the significant protective effect of increased ANM documented in an observational analysis of roughly the same data as well as prior reports that did not use MR. This “notable inconsistency” suggests very substantial residual confounding without MR that could be driven by factors such as smoking, diet, and exercise.
• If these results are replicated in additional datasets, it would highlight a need for randomized, controlled trials of antiestrogen therapies in postmenopausal women for the prevention or treatment of lung cancer.

Study design

• The study included data from 106,853 postmenopausal women enrolled in the Women’s Health Initiative (WHI) and 95,464 women who were 37-73 years old included in the UK Biobank (UKB). Analyses for each outcome also included data from smaller numbers of women obtained from several additional datasets.
• The MR analysis used up to 55 single-nucleotide polymorphisms previously discovered through a genome-wide association study of about 70,000 women of European ancestry and independent of all datasets analyzed in the current study. The authors included all single-nucleotide polymorphisms with a consistent direction of effect on ANM.
• The MR analysis for lung cancer included 113,371 women from the two primary datasets and an additional 3012 women from six additional datasets.
• The MR analysis for bone fracture involved 113,239 women from the WHI and UKB only. The MR analysis for osteoporosis involved 137,080 women from the WHI, UKB, and one additional external dataset.

Key results

• Results from a meta-analysis of the MR results using data from the WHI, UKB, and the additional datasets showed ANM was causally associated with an increased risk of lung cancer by an odds ratio of 1.35 for each 5-year increase in ANM. In contrast, the adjusted observational analysis of data just from the WHI and UKB showed a significant 11% relative risk reduction in the incidence of lung cancer for each 5-year increase in ANM.
• The MR results also showed causally protective effects for fracture, with a 24% relative risk reduction, and for osteoporosis, with a 19% relative risk reduction for each 5-year increase in ANM.
• The MR analyses showed no significant association between AMN and outcome for breast cancer, endometrial cancer, ovarian cancer, coronary heart disease, ischemic stroke, and Alzheimer’s disease.

Limitations

The main limitation of the MR study was the potential for inadequate power for assessing some outcomes despite the large overall size of the study cohort. Lack of adequate power may be responsible for some of the nonsignificant associations seen in the study, such as for breast and endometrial cancers, where substantial prior evidence has implicated increased risk through the effects of prolonged exposure to endogenous or exogenous estrogens.

The healthy cohort effect in the UKB is a known weakness of this dataset that may have limited the number of cases and generalizability of findings.

Osteoporosis and Alzheimer’s disease were self-reported.

The study only included participants of European ancestry because most subjects in most of the cohorts examined were White women and the applied MR instruments were found by genome-wide association studies run predominantly in White women. The authors said the causal effects of ANM need study in more diverse populations.
 

Disclosures

• The study received no commercial funding.
• None of the authors had disclosures.

This is a summary of a preprint research study, “Genetic evidence for causal relationships between age at natural menopause and the risk of aging-associated adverse health outcomes,” written by authors primarily based at Stanford University School of Medicine i

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

This study was published on Medrxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• in analyses of more than 100,000 women that used Mendelian randomization (MR) as a tool to reduce residual confounding.
• The MR analyses showed no significant association between ANM and breast cancer, endometrial cancer, ovarian cancer, coronary heart disease, ischemic stroke, and Alzheimer’s disease.
• The clear lack of a causal effect of ANM on the outcomes of coronary heart disease and ischemic stroke in the MR analyses despite a strong inverse association seen in the observational data of this study (without MR) suggests residual confounding plays a substantial role in driving the observed outcomes.

Why this matters

• The authors said that, to their knowledge, this is the first study that has shown a causal association between older ANM and higher risk of postmenopausal lung cancer.
• This finding was directionally opposite to the significant protective effect of increased ANM documented in an observational analysis of roughly the same data as well as prior reports that did not use MR. This “notable inconsistency” suggests very substantial residual confounding without MR that could be driven by factors such as smoking, diet, and exercise.
• If these results are replicated in additional datasets, it would highlight a need for randomized, controlled trials of antiestrogen therapies in postmenopausal women for the prevention or treatment of lung cancer.

Study design

• The study included data from 106,853 postmenopausal women enrolled in the Women’s Health Initiative (WHI) and 95,464 women who were 37-73 years old included in the UK Biobank (UKB). Analyses for each outcome also included data from smaller numbers of women obtained from several additional datasets.
• The MR analysis used up to 55 single-nucleotide polymorphisms previously discovered through a genome-wide association study of about 70,000 women of European ancestry and independent of all datasets analyzed in the current study. The authors included all single-nucleotide polymorphisms with a consistent direction of effect on ANM.
• The MR analysis for lung cancer included 113,371 women from the two primary datasets and an additional 3012 women from six additional datasets.
• The MR analysis for bone fracture involved 113,239 women from the WHI and UKB only. The MR analysis for osteoporosis involved 137,080 women from the WHI, UKB, and one additional external dataset.

Key results

• Results from a meta-analysis of the MR results using data from the WHI, UKB, and the additional datasets showed ANM was causally associated with an increased risk of lung cancer by an odds ratio of 1.35 for each 5-year increase in ANM. In contrast, the adjusted observational analysis of data just from the WHI and UKB showed a significant 11% relative risk reduction in the incidence of lung cancer for each 5-year increase in ANM.
• The MR results also showed causally protective effects for fracture, with a 24% relative risk reduction, and for osteoporosis, with a 19% relative risk reduction for each 5-year increase in ANM.
• The MR analyses showed no significant association between AMN and outcome for breast cancer, endometrial cancer, ovarian cancer, coronary heart disease, ischemic stroke, and Alzheimer’s disease.

Limitations

The main limitation of the MR study was the potential for inadequate power for assessing some outcomes despite the large overall size of the study cohort. Lack of adequate power may be responsible for some of the nonsignificant associations seen in the study, such as for breast and endometrial cancers, where substantial prior evidence has implicated increased risk through the effects of prolonged exposure to endogenous or exogenous estrogens.

The healthy cohort effect in the UKB is a known weakness of this dataset that may have limited the number of cases and generalizability of findings.

Osteoporosis and Alzheimer’s disease were self-reported.

The study only included participants of European ancestry because most subjects in most of the cohorts examined were White women and the applied MR instruments were found by genome-wide association studies run predominantly in White women. The authors said the causal effects of ANM need study in more diverse populations.
 

Disclosures

• The study received no commercial funding.
• None of the authors had disclosures.

This is a summary of a preprint research study, “Genetic evidence for causal relationships between age at natural menopause and the risk of aging-associated adverse health outcomes,” written by authors primarily based at Stanford University School of Medicine i

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

Early initiation of the antiviral oseltamivir (Tamiflu) reduces the risk for death in patients hospitalized with community-acquired pneumonia (CAP) but patients have to be tested for influenza first and that is not happening often enough, a large observational cohort of adult patients indicates.

“Early testing allows for early treatment, and we found that early treatment was associated with reduced mortality so testing patients during the flu season is crucial,” senior author Michael Rothberg, MD, MPH, of the Cleveland Clinic said in an interview.

“Even during the flu season, most patients with CAP in our study went untested for influenza [even though] those who received early oseltamivir exhibited lower 14-day in-hospital case fatality ... suggesting more widespread testing might improve patient outcomes,” the authors added.

The study was published online Feb. 5, 2022, in the journal CHEST.
 

Premier database

Data from the Premier Database – a hospital discharge database with information from over 600 hospitals in the United States – were analyzed between July 2010 and June 2015. Microbiological laboratory data was provided by 179 hospitals. “For each year, we evaluated the total percentage of patients tested for influenza A/B within 3 days of hospitalization,” lead author Abhishek Deshpande, MD, PhD, Cleveland Clinic, and colleagues explained.

A total of 166,268 patients with CAP were included in the study, among which only about one-quarter were tested for influenza. Some 11.5% tested positive for the flu, the authors noted. Testing did increase from 15.4% in 2010 to 35.6% in 2015 and it was higher at close to 29% during the influenza season, compared with only about 8% during the summer months.

Patients who were tested for influenza were younger at age 66.6 years, compared with untested patients, who were 70 years of age (P < .001). Tested patients were also less likely to have been admitted from a nursing facility (P < .001), were less likely to have been hospitalized in the preceding 6 months (P < .001) and have fewer comorbidities than those who were not tested (P < .001).

“Both groups had similar illness severities on admission,” the authors observed, “but patients who were tested were less likely to die in the hospital within 14 days,” the authors reported – at 6.7% versus 10.9% for untested patients (P < .001).

More than 80% of patients who tested positive for influenza received an antibacterial on day 1 of their admission, compared with virtually all those who were either not tested or who tested negative, the investigators added (P < .001). The mean duration of antibacterial therapy among patients with a bacterial coinfection was not influenced by influenza test results.

However, among those who tested positive for influenza, almost 60% received oseltamivir on day 1 whereas roughly 30% received treatment on day 2 or later. In fact, almost all patients who received early oseltamivir were tested for influenza on day 1, the investigators pointed out. Patients who received early oseltamivir had a 25% lower risk of death within the first 14 days in hospital at an adjusted odds ratio of 0.75 (95% confidence interval, 0.59-0.96).

Early initiation of the antiviral also reduced the risk of requiring subsequent ICU care by 36% at an aOR of 0.64; invasive mechanical ventilation by 46% at an aOR of 0.54, and the need for vasopressor therapy by 47% at an aOR of 0.53. All results were within the 95% confidence levels.

Early use of antiviral therapy also reduced both the length of hospital stay and the cost of that stay by 12%.
 

ATS-IDSA guidelines

As Dr. Deshpande noted, the American Thoracic Society and the Infectious Diseases Society of America guidelines recommend testing and empiric treatment of influenza in patients hospitalized with CAP. “Testing more inpatients especially during the flu season can reduce other diagnostic testing and improve antimicrobial stewardship,” Deshpande noted.

Thus, while the rate of testing for influenza did increase over the 5-year study interval, “there is substantial room for improvement,” he added, as a positive test clearly does trigger the need for intervention. As Dr. Deshpande also noted, the past two influenza seasons have been mild, but influenza activity has again picked up lately again in many parts of the United States.

With the COVID-19 pandemic overwhelming influenza over the past few years, “differentiating between the two based on symptoms alone can be challenging,” he acknowledged, “and clinicians will need to test and treat accordingly.” This is particularly important given that this study clearly indicates that early treatment with an antiviral can lower the risk of short-term mortality in hospitalized CAP patients.

One limitation of the study was the lack of data on time of symptom onset, which may be an important confounder of the effect of oseltamivir on outcomes, the authors point out. Asked to comment on the findings, Barbara Jones, MD, University of Utah Health, Salt Lake City, noted that timely antivirals for patients with influenza are highly effective at mitigating severe disease and are thus strongly recommended by practice guidelines.

“However, it is hard for clinicians to keep influenza on the radar and change testing and treatment approaches according to the season and prevalence [of influenza infections],” she said in an interview. “This is an important study that highlights this challenge.

“We need a better understanding of the solutions that have been effective at improving influenza recognition and treatment, possibly by studying facilities that perform well at this process,” she said.

Dr. Deshpande reported receiving research funding to his institution from the Clorox Company and consultant fees from Merck.

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

Early initiation of the antiviral oseltamivir (Tamiflu) reduces the risk for death in patients hospitalized with community-acquired pneumonia (CAP) but patients have to be tested for influenza first and that is not happening often enough, a large observational cohort of adult patients indicates.

“Early testing allows for early treatment, and we found that early treatment was associated with reduced mortality so testing patients during the flu season is crucial,” senior author Michael Rothberg, MD, MPH, of the Cleveland Clinic said in an interview.

“Even during the flu season, most patients with CAP in our study went untested for influenza [even though] those who received early oseltamivir exhibited lower 14-day in-hospital case fatality ... suggesting more widespread testing might improve patient outcomes,” the authors added.

The study was published online Feb. 5, 2022, in the journal CHEST.
 

Premier database

Data from the Premier Database – a hospital discharge database with information from over 600 hospitals in the United States – were analyzed between July 2010 and June 2015. Microbiological laboratory data was provided by 179 hospitals. “For each year, we evaluated the total percentage of patients tested for influenza A/B within 3 days of hospitalization,” lead author Abhishek Deshpande, MD, PhD, Cleveland Clinic, and colleagues explained.

A total of 166,268 patients with CAP were included in the study, among which only about one-quarter were tested for influenza. Some 11.5% tested positive for the flu, the authors noted. Testing did increase from 15.4% in 2010 to 35.6% in 2015 and it was higher at close to 29% during the influenza season, compared with only about 8% during the summer months.

Patients who were tested for influenza were younger at age 66.6 years, compared with untested patients, who were 70 years of age (P < .001). Tested patients were also less likely to have been admitted from a nursing facility (P < .001), were less likely to have been hospitalized in the preceding 6 months (P < .001) and have fewer comorbidities than those who were not tested (P < .001).

“Both groups had similar illness severities on admission,” the authors observed, “but patients who were tested were less likely to die in the hospital within 14 days,” the authors reported – at 6.7% versus 10.9% for untested patients (P < .001).

More than 80% of patients who tested positive for influenza received an antibacterial on day 1 of their admission, compared with virtually all those who were either not tested or who tested negative, the investigators added (P < .001). The mean duration of antibacterial therapy among patients with a bacterial coinfection was not influenced by influenza test results.

However, among those who tested positive for influenza, almost 60% received oseltamivir on day 1 whereas roughly 30% received treatment on day 2 or later. In fact, almost all patients who received early oseltamivir were tested for influenza on day 1, the investigators pointed out. Patients who received early oseltamivir had a 25% lower risk of death within the first 14 days in hospital at an adjusted odds ratio of 0.75 (95% confidence interval, 0.59-0.96).

Early initiation of the antiviral also reduced the risk of requiring subsequent ICU care by 36% at an aOR of 0.64; invasive mechanical ventilation by 46% at an aOR of 0.54, and the need for vasopressor therapy by 47% at an aOR of 0.53. All results were within the 95% confidence levels.

Early use of antiviral therapy also reduced both the length of hospital stay and the cost of that stay by 12%.
 

ATS-IDSA guidelines

As Dr. Deshpande noted, the American Thoracic Society and the Infectious Diseases Society of America guidelines recommend testing and empiric treatment of influenza in patients hospitalized with CAP. “Testing more inpatients especially during the flu season can reduce other diagnostic testing and improve antimicrobial stewardship,” Deshpande noted.

Thus, while the rate of testing for influenza did increase over the 5-year study interval, “there is substantial room for improvement,” he added, as a positive test clearly does trigger the need for intervention. As Dr. Deshpande also noted, the past two influenza seasons have been mild, but influenza activity has again picked up lately again in many parts of the United States.

With the COVID-19 pandemic overwhelming influenza over the past few years, “differentiating between the two based on symptoms alone can be challenging,” he acknowledged, “and clinicians will need to test and treat accordingly.” This is particularly important given that this study clearly indicates that early treatment with an antiviral can lower the risk of short-term mortality in hospitalized CAP patients.

One limitation of the study was the lack of data on time of symptom onset, which may be an important confounder of the effect of oseltamivir on outcomes, the authors point out. Asked to comment on the findings, Barbara Jones, MD, University of Utah Health, Salt Lake City, noted that timely antivirals for patients with influenza are highly effective at mitigating severe disease and are thus strongly recommended by practice guidelines.

“However, it is hard for clinicians to keep influenza on the radar and change testing and treatment approaches according to the season and prevalence [of influenza infections],” she said in an interview. “This is an important study that highlights this challenge.

“We need a better understanding of the solutions that have been effective at improving influenza recognition and treatment, possibly by studying facilities that perform well at this process,” she said.

Dr. Deshpande reported receiving research funding to his institution from the Clorox Company and consultant fees from Merck.

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

Early initiation of the antiviral oseltamivir (Tamiflu) reduces the risk for death in patients hospitalized with community-acquired pneumonia (CAP) but patients have to be tested for influenza first and that is not happening often enough, a large observational cohort of adult patients indicates.

“Early testing allows for early treatment, and we found that early treatment was associated with reduced mortality so testing patients during the flu season is crucial,” senior author Michael Rothberg, MD, MPH, of the Cleveland Clinic said in an interview.

“Even during the flu season, most patients with CAP in our study went untested for influenza [even though] those who received early oseltamivir exhibited lower 14-day in-hospital case fatality ... suggesting more widespread testing might improve patient outcomes,” the authors added.

The study was published online Feb. 5, 2022, in the journal CHEST.
 

Premier database

Data from the Premier Database – a hospital discharge database with information from over 600 hospitals in the United States – were analyzed between July 2010 and June 2015. Microbiological laboratory data was provided by 179 hospitals. “For each year, we evaluated the total percentage of patients tested for influenza A/B within 3 days of hospitalization,” lead author Abhishek Deshpande, MD, PhD, Cleveland Clinic, and colleagues explained.

A total of 166,268 patients with CAP were included in the study, among which only about one-quarter were tested for influenza. Some 11.5% tested positive for the flu, the authors noted. Testing did increase from 15.4% in 2010 to 35.6% in 2015 and it was higher at close to 29% during the influenza season, compared with only about 8% during the summer months.

Patients who were tested for influenza were younger at age 66.6 years, compared with untested patients, who were 70 years of age (P < .001). Tested patients were also less likely to have been admitted from a nursing facility (P < .001), were less likely to have been hospitalized in the preceding 6 months (P < .001) and have fewer comorbidities than those who were not tested (P < .001).

“Both groups had similar illness severities on admission,” the authors observed, “but patients who were tested were less likely to die in the hospital within 14 days,” the authors reported – at 6.7% versus 10.9% for untested patients (P < .001).

More than 80% of patients who tested positive for influenza received an antibacterial on day 1 of their admission, compared with virtually all those who were either not tested or who tested negative, the investigators added (P < .001). The mean duration of antibacterial therapy among patients with a bacterial coinfection was not influenced by influenza test results.

However, among those who tested positive for influenza, almost 60% received oseltamivir on day 1 whereas roughly 30% received treatment on day 2 or later. In fact, almost all patients who received early oseltamivir were tested for influenza on day 1, the investigators pointed out. Patients who received early oseltamivir had a 25% lower risk of death within the first 14 days in hospital at an adjusted odds ratio of 0.75 (95% confidence interval, 0.59-0.96).

Early initiation of the antiviral also reduced the risk of requiring subsequent ICU care by 36% at an aOR of 0.64; invasive mechanical ventilation by 46% at an aOR of 0.54, and the need for vasopressor therapy by 47% at an aOR of 0.53. All results were within the 95% confidence levels.

Early use of antiviral therapy also reduced both the length of hospital stay and the cost of that stay by 12%.
 

ATS-IDSA guidelines

As Dr. Deshpande noted, the American Thoracic Society and the Infectious Diseases Society of America guidelines recommend testing and empiric treatment of influenza in patients hospitalized with CAP. “Testing more inpatients especially during the flu season can reduce other diagnostic testing and improve antimicrobial stewardship,” Deshpande noted.

Thus, while the rate of testing for influenza did increase over the 5-year study interval, “there is substantial room for improvement,” he added, as a positive test clearly does trigger the need for intervention. As Dr. Deshpande also noted, the past two influenza seasons have been mild, but influenza activity has again picked up lately again in many parts of the United States.

With the COVID-19 pandemic overwhelming influenza over the past few years, “differentiating between the two based on symptoms alone can be challenging,” he acknowledged, “and clinicians will need to test and treat accordingly.” This is particularly important given that this study clearly indicates that early treatment with an antiviral can lower the risk of short-term mortality in hospitalized CAP patients.

One limitation of the study was the lack of data on time of symptom onset, which may be an important confounder of the effect of oseltamivir on outcomes, the authors point out. Asked to comment on the findings, Barbara Jones, MD, University of Utah Health, Salt Lake City, noted that timely antivirals for patients with influenza are highly effective at mitigating severe disease and are thus strongly recommended by practice guidelines.

“However, it is hard for clinicians to keep influenza on the radar and change testing and treatment approaches according to the season and prevalence [of influenza infections],” she said in an interview. “This is an important study that highlights this challenge.

“We need a better understanding of the solutions that have been effective at improving influenza recognition and treatment, possibly by studying facilities that perform well at this process,” she said.

Dr. Deshpande reported receiving research funding to his institution from the Clorox Company and consultant fees from Merck.

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

The American Academy of Pediatrics said it supports the Recommended Childhood and Adolescent Immunization Schedule: United States, 2022.

In a policy statement published online Feb. 17 in Pediatrics, the AAP said the updated recommendations differ little from those released last year by the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.

“The only significant change this year was to add the dengue vaccine to the schedule,” Sean T. O’Leary, MD, MPH, vice chair of the AAP’s 2021-2022 Committee on Infectious Diseases and a coauthor of the statement, told this news organization. “But that is really only relevant for children living in endemic areas, primarily Puerto Rico but some other smaller U.S .territories as well.”

Dengue fever also is endemic in American Samoa and the U.S. Virgin Islands.

Notably, a new section has been added on routine recommendations for use of the Dengvaxia vaccine.

The 2022 policy statement addresses regular immunization of children from birth to 18 years and catch-up vaccination for those aged 4 months to 18 years. In addition to the AAP, multiple complementary physician and nurse organizations have approved the updates. The ACIP schedule is revised annually to reflect current recommendations on vaccines licensed by the U.S. Food and Drug Administration.

Most of the other changes this year involve minor updates to clarify language or improve usability. “CDC and AAP are always working to make the schedule as user-friendly as possible, with improvements made every year,” Dr. O’Leary, professor of pediatric infectious diseases at the University of Colorado at Denver, Aurora, said.

In terms of physician acceptance, he added, “I don’t think any of the changes would be considered controversial.”

Among other updates and clarifications:

• For Haemophilus influenzae type b (Hib) vaccination, the text now includes recommendations for the hexavalent Vaxelis vaccine (diphtheria, tetanus, pertussis, polio, Hib, and hepatitis B) for both routine and catch-up vaccination.
• For hepatitis A, the relevant note has been updated to clarify the age for routine vaccination.
• For human papillomavirus (HPV), the note now clarifies when an HPV series is complete with no additional dose recommended.
• The special situations section has been amended to specify which persons with immunocompromising conditions such as HIV should receive three doses of HPV vaccine regardless of age at initial vaccination.
• For measles, mumps, and rubella, routine vaccination now includes recommendations on the combination measles, mumps, rubella, and varicella vaccine.
• For meningococcal serogroup A, C, W, and Y vaccines, the augmented text explains when these can be simultaneously administered with serogroup B meningococcal vaccines, preferably at different anatomic sites. The language for the dosing schedule for Menveo vaccination in infants also has been clarified.
• In the catch-up immunization schedule for late-starting children aged 4 months to 18 years, the text on Hib has been changed so that the minimum interval between dose two and dose three now refers to Vaxelis, while reference to the discontinued Comvax (Hib-Hep B) vaccine has been removed.

As in other years, graphic changes have been made to table coloration and layout to improve accessibility. And as before, the 2022 childhood and adolescent immunization schedule has been updated to ensure consistency between its format and that of the 2022 adult immunization schedules.

The AAP committee stressed that clinically significant adverse events after immunization should be reported to the Vaccine Adverse Event Reporting System.

The full 2022 schedule can be found on the CDC’s website.

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

The American Academy of Pediatrics said it supports the Recommended Childhood and Adolescent Immunization Schedule: United States, 2022.

In a policy statement published online Feb. 17 in Pediatrics, the AAP said the updated recommendations differ little from those released last year by the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.

“The only significant change this year was to add the dengue vaccine to the schedule,” Sean T. O’Leary, MD, MPH, vice chair of the AAP’s 2021-2022 Committee on Infectious Diseases and a coauthor of the statement, told this news organization. “But that is really only relevant for children living in endemic areas, primarily Puerto Rico but some other smaller U.S .territories as well.”

Dengue fever also is endemic in American Samoa and the U.S. Virgin Islands.

Notably, a new section has been added on routine recommendations for use of the Dengvaxia vaccine.

The 2022 policy statement addresses regular immunization of children from birth to 18 years and catch-up vaccination for those aged 4 months to 18 years. In addition to the AAP, multiple complementary physician and nurse organizations have approved the updates. The ACIP schedule is revised annually to reflect current recommendations on vaccines licensed by the U.S. Food and Drug Administration.

Most of the other changes this year involve minor updates to clarify language or improve usability. “CDC and AAP are always working to make the schedule as user-friendly as possible, with improvements made every year,” Dr. O’Leary, professor of pediatric infectious diseases at the University of Colorado at Denver, Aurora, said.

In terms of physician acceptance, he added, “I don’t think any of the changes would be considered controversial.”

Among other updates and clarifications:

• For Haemophilus influenzae type b (Hib) vaccination, the text now includes recommendations for the hexavalent Vaxelis vaccine (diphtheria, tetanus, pertussis, polio, Hib, and hepatitis B) for both routine and catch-up vaccination.
• For hepatitis A, the relevant note has been updated to clarify the age for routine vaccination.
• For human papillomavirus (HPV), the note now clarifies when an HPV series is complete with no additional dose recommended.
• The special situations section has been amended to specify which persons with immunocompromising conditions such as HIV should receive three doses of HPV vaccine regardless of age at initial vaccination.
• For measles, mumps, and rubella, routine vaccination now includes recommendations on the combination measles, mumps, rubella, and varicella vaccine.
• For meningococcal serogroup A, C, W, and Y vaccines, the augmented text explains when these can be simultaneously administered with serogroup B meningococcal vaccines, preferably at different anatomic sites. The language for the dosing schedule for Menveo vaccination in infants also has been clarified.
• In the catch-up immunization schedule for late-starting children aged 4 months to 18 years, the text on Hib has been changed so that the minimum interval between dose two and dose three now refers to Vaxelis, while reference to the discontinued Comvax (Hib-Hep B) vaccine has been removed.

As in other years, graphic changes have been made to table coloration and layout to improve accessibility. And as before, the 2022 childhood and adolescent immunization schedule has been updated to ensure consistency between its format and that of the 2022 adult immunization schedules.

The AAP committee stressed that clinically significant adverse events after immunization should be reported to the Vaccine Adverse Event Reporting System.

The full 2022 schedule can be found on the CDC’s website.

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

The American Academy of Pediatrics said it supports the Recommended Childhood and Adolescent Immunization Schedule: United States, 2022.

In a policy statement published online Feb. 17 in Pediatrics, the AAP said the updated recommendations differ little from those released last year by the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.

“The only significant change this year was to add the dengue vaccine to the schedule,” Sean T. O’Leary, MD, MPH, vice chair of the AAP’s 2021-2022 Committee on Infectious Diseases and a coauthor of the statement, told this news organization. “But that is really only relevant for children living in endemic areas, primarily Puerto Rico but some other smaller U.S .territories as well.”

Dengue fever also is endemic in American Samoa and the U.S. Virgin Islands.

Notably, a new section has been added on routine recommendations for use of the Dengvaxia vaccine.

The 2022 policy statement addresses regular immunization of children from birth to 18 years and catch-up vaccination for those aged 4 months to 18 years. In addition to the AAP, multiple complementary physician and nurse organizations have approved the updates. The ACIP schedule is revised annually to reflect current recommendations on vaccines licensed by the U.S. Food and Drug Administration.

Most of the other changes this year involve minor updates to clarify language or improve usability. “CDC and AAP are always working to make the schedule as user-friendly as possible, with improvements made every year,” Dr. O’Leary, professor of pediatric infectious diseases at the University of Colorado at Denver, Aurora, said.

In terms of physician acceptance, he added, “I don’t think any of the changes would be considered controversial.”

Among other updates and clarifications:

• For Haemophilus influenzae type b (Hib) vaccination, the text now includes recommendations for the hexavalent Vaxelis vaccine (diphtheria, tetanus, pertussis, polio, Hib, and hepatitis B) for both routine and catch-up vaccination.
• For hepatitis A, the relevant note has been updated to clarify the age for routine vaccination.
• For human papillomavirus (HPV), the note now clarifies when an HPV series is complete with no additional dose recommended.
• The special situations section has been amended to specify which persons with immunocompromising conditions such as HIV should receive three doses of HPV vaccine regardless of age at initial vaccination.
• For measles, mumps, and rubella, routine vaccination now includes recommendations on the combination measles, mumps, rubella, and varicella vaccine.
• For meningococcal serogroup A, C, W, and Y vaccines, the augmented text explains when these can be simultaneously administered with serogroup B meningococcal vaccines, preferably at different anatomic sites. The language for the dosing schedule for Menveo vaccination in infants also has been clarified.
• In the catch-up immunization schedule for late-starting children aged 4 months to 18 years, the text on Hib has been changed so that the minimum interval between dose two and dose three now refers to Vaxelis, while reference to the discontinued Comvax (Hib-Hep B) vaccine has been removed.

As in other years, graphic changes have been made to table coloration and layout to improve accessibility. And as before, the 2022 childhood and adolescent immunization schedule has been updated to ensure consistency between its format and that of the 2022 adult immunization schedules.

The AAP committee stressed that clinically significant adverse events after immunization should be reported to the Vaccine Adverse Event Reporting System.

The full 2022 schedule can be found on the CDC’s website.

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

The Centers for Medicare & Medicaid Services (CMS) will expand eligibility guidelines for lung cancer screening with low-dose computed tomography for Medicare recipients.

According to the final decision, announced February 10, CMS will lower the age for screening from 55 to 50 years up to 77 years and reduce criteria for tobacco smoking history from at least 30 pack-years to 20 pack-years. The expanded Medicare recommendation will address racial disparities associated with lung cancer, given evidence that one third of Black patients are diagnosed with lung cancer before age 55.

The updated CMS guidelines align closely with recommendations made by the U.S. Preventive Services Task Force (USPSTF) in March 2021. The USPSTF expanded its guidelines for screening to include individuals ages 50 to 80 years, as well as those who have a 20–pack-year smoking history and who currently smoke or have quit within the past 15 years.

Overall, the expanded guidelines will nearly double the number of individuals who are eligible for screening and have the potential to save significantly more lives by identifying cancers at an earlier, more treatable stage.

“Expanding coverage broadens access for lung cancer screening to at-risk populations,” said Lee Felisher, MD, CMS chief medical officer and director of the Center for Clinical Standards and Quality, in a statement. “Today’s decision not only expands access to quality care but is also critical to improving health outcomes for people by helping to detect lung cancer earlier.”

CMS’s decision also simplifies requirements for counseling and shared decision-making visits and removes an initial requirement for the reading radiologist to document participation in continuing medical education, which will reduce administrative burden. CMS also added a requirement back to the National Coverage Determination criteria that requires radiology imaging facilities to use a standardized lung nodule identification, classification, and reporting system.

The American Lung Association applauds the decision to update eligibility.

“[The] announcement from CMS will give more people enrolled in Medicare access to lifesaving lung cancer screening. Screening for individuals at high risk is the only tool to catch this disease early when it is more curable,” Harold Wimmer, president and CEO of the American Lung Association, said in a statement. “Unfortunately, only 5.7% of people who are eligible have been screened, so it’s important that we talk with our friends and family who are at high risk about getting screened.”

While access to screening will significantly increase, the American Lung Association recommends CMS go a step further and expand eligibility to individuals up to 80 years of age, as the USPSTF recommendations do, as well as remove the recommendation that individuals cease screening once they have stopped smoking for 15 years.

Given the new guidelines, most private insurance plans will need to update screening coverage policies to reflect the updated guidelines for plan years beginning after March 31.

To read the final decision, visit the CMS website.

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

The Centers for Medicare & Medicaid Services (CMS) will expand eligibility guidelines for lung cancer screening with low-dose computed tomography for Medicare recipients.

According to the final decision, announced February 10, CMS will lower the age for screening from 55 to 50 years up to 77 years and reduce criteria for tobacco smoking history from at least 30 pack-years to 20 pack-years. The expanded Medicare recommendation will address racial disparities associated with lung cancer, given evidence that one third of Black patients are diagnosed with lung cancer before age 55.

The updated CMS guidelines align closely with recommendations made by the U.S. Preventive Services Task Force (USPSTF) in March 2021. The USPSTF expanded its guidelines for screening to include individuals ages 50 to 80 years, as well as those who have a 20–pack-year smoking history and who currently smoke or have quit within the past 15 years.

Overall, the expanded guidelines will nearly double the number of individuals who are eligible for screening and have the potential to save significantly more lives by identifying cancers at an earlier, more treatable stage.

“Expanding coverage broadens access for lung cancer screening to at-risk populations,” said Lee Felisher, MD, CMS chief medical officer and director of the Center for Clinical Standards and Quality, in a statement. “Today’s decision not only expands access to quality care but is also critical to improving health outcomes for people by helping to detect lung cancer earlier.”

CMS’s decision also simplifies requirements for counseling and shared decision-making visits and removes an initial requirement for the reading radiologist to document participation in continuing medical education, which will reduce administrative burden. CMS also added a requirement back to the National Coverage Determination criteria that requires radiology imaging facilities to use a standardized lung nodule identification, classification, and reporting system.

The American Lung Association applauds the decision to update eligibility.

“[The] announcement from CMS will give more people enrolled in Medicare access to lifesaving lung cancer screening. Screening for individuals at high risk is the only tool to catch this disease early when it is more curable,” Harold Wimmer, president and CEO of the American Lung Association, said in a statement. “Unfortunately, only 5.7% of people who are eligible have been screened, so it’s important that we talk with our friends and family who are at high risk about getting screened.”

While access to screening will significantly increase, the American Lung Association recommends CMS go a step further and expand eligibility to individuals up to 80 years of age, as the USPSTF recommendations do, as well as remove the recommendation that individuals cease screening once they have stopped smoking for 15 years.

Given the new guidelines, most private insurance plans will need to update screening coverage policies to reflect the updated guidelines for plan years beginning after March 31.

To read the final decision, visit the CMS website.

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

The Centers for Medicare & Medicaid Services (CMS) will expand eligibility guidelines for lung cancer screening with low-dose computed tomography for Medicare recipients.

According to the final decision, announced February 10, CMS will lower the age for screening from 55 to 50 years up to 77 years and reduce criteria for tobacco smoking history from at least 30 pack-years to 20 pack-years. The expanded Medicare recommendation will address racial disparities associated with lung cancer, given evidence that one third of Black patients are diagnosed with lung cancer before age 55.

The updated CMS guidelines align closely with recommendations made by the U.S. Preventive Services Task Force (USPSTF) in March 2021. The USPSTF expanded its guidelines for screening to include individuals ages 50 to 80 years, as well as those who have a 20–pack-year smoking history and who currently smoke or have quit within the past 15 years.

Overall, the expanded guidelines will nearly double the number of individuals who are eligible for screening and have the potential to save significantly more lives by identifying cancers at an earlier, more treatable stage.

“Expanding coverage broadens access for lung cancer screening to at-risk populations,” said Lee Felisher, MD, CMS chief medical officer and director of the Center for Clinical Standards and Quality, in a statement. “Today’s decision not only expands access to quality care but is also critical to improving health outcomes for people by helping to detect lung cancer earlier.”

CMS’s decision also simplifies requirements for counseling and shared decision-making visits and removes an initial requirement for the reading radiologist to document participation in continuing medical education, which will reduce administrative burden. CMS also added a requirement back to the National Coverage Determination criteria that requires radiology imaging facilities to use a standardized lung nodule identification, classification, and reporting system.

The American Lung Association applauds the decision to update eligibility.

“[The] announcement from CMS will give more people enrolled in Medicare access to lifesaving lung cancer screening. Screening for individuals at high risk is the only tool to catch this disease early when it is more curable,” Harold Wimmer, president and CEO of the American Lung Association, said in a statement. “Unfortunately, only 5.7% of people who are eligible have been screened, so it’s important that we talk with our friends and family who are at high risk about getting screened.”

While access to screening will significantly increase, the American Lung Association recommends CMS go a step further and expand eligibility to individuals up to 80 years of age, as the USPSTF recommendations do, as well as remove the recommendation that individuals cease screening once they have stopped smoking for 15 years.

Given the new guidelines, most private insurance plans will need to update screening coverage policies to reflect the updated guidelines for plan years beginning after March 31.

To read the final decision, visit the CMS website.

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

Use of positive airway pressure (PAP) devices for treatment of sleep apnea was first described in 1981. Subsequent use of PAP devices expanded to treat patients with respiratory failure. While the treatment in this population has rapidly gained widespread use and undoubtedly has reduced morbidity and mortality in these populations, policies governing these prescriptions have not really kept up with the burgeoning need.

In 2020, Drs. Peter Gay and Robert Owens brought together a technical expert panel (TEP) to systematically review the CMS policies with an eye to remove “regulatory barriers” to improve access for these patients with the mantra: “the right device gets to the right patient at the right time.”

The panel focused on “Optimal NIV Medicare Access Promotion (ONMAP),” and members with specific expertise were recruited for five patient groups: Thoracic Restrictive Disorders (TRD), COPD, Central Sleep Apnea (CSA), Hypoventilation Syndromes (HVS), and Obstructive Sleep Apnea (OSA). Each group reviewed the current coverage, outlined the deficiencies, and suggested revisions. Herein, I will briefly highlight each group’s most important points.
 

TRD: The goal for this group was to bring the US standards of care closer to the rest of the world. This group advocates that the start of noninvasive ventilation (NIV) should be substantially earlier, to provide the largest improvement in disease outcome and stability. Other prominent features submitted included arterial blood gases (ABG) to not be the only form of CO₂ measurement allowed; paying for a second device if patients are using NIV continuously; qualification for a BiPAP to include if vital capacity is ≤ 80%; and, to obtain a home mechanical ventilator, a patient must either fail BiPAP or have extreme loss of function, high pressure requirements, or need mouthpiece ventilation.

CSA: The big challenges with this diagnosis related to qualifying coverage language in the current policies, which are confusing for many providers. Additionally, these policies often deny certain PAP devices and/or oxygen therapy. The group proposed: a single definition of CSA; eliminate discussion of hypoventilation; mirror qualifying symptoms, and, continuing coverage, to the same as that for OSA treatment; and remove need for a prior failure of BiPAP without a backup rate (BUR). The group also had specific recommendations for when oxygen therapy should be covered in patients with CSA.

COPD: This group also focused on the oxygen therapy and promoting use of devices with a BUR. Two problematic areas included the requirement that nocturnal oxygen saturation must drop to ≤ 88% for at least 5 cumulative minutes, and, that patients must begin with an S mode device (no BUR) for at least 2 months and can only then be prescribed a device with a BUR if CO₂ fails to drop. The group advocates for the removal of both, the need for a nocturnal oximetry test, and, to “try” an S mode device. The panel advocated giving the prescribing physician discretion in making this determination. The panel also provided recommendations on when a home mechanical ventilator (HMV) should be considered instead of BiPAP therapy.

HVS: Hypoventilation syndromes are a heterogeneous group of disorders with hypercapnia, defined as a Paco₂ ≥45 mm Hg. This panel noted that the current coverage criteria are outdated and fail to recognize the spectrum of disease severity and advances in technology, which often leads to circumvention by prescribing more costly home mechanical ventilators (HMV). Consistent with the TRD group, this panel recommended acceptance of surrogate noninvasive end tidal and transcutaneous Pco₂ and venous blood gases in lieu of arterial blood gases. Additionally, they suggested no longer requiring CO₂ measures while using prescribed oxygen; eliminating the need for a sleep study to avoid delays in care for patients being discharged from the hospital; removing spirometry as a requirement; and no longer a failure of BiPAP without a BUR.

OSA: The initial purpose of examining OSA in this process was to examine when BiPAP should be utilized for treatment; however, it necessitated examination of the entire policy for PAP. The areas that were identified as needing revision included: expansion of the symptom list for patients with OSA; revising the “4 hour rule,” suggesting that 2 hours has been proven to provide benefit; eliminating the need for another sleep study to re-qualify for PAP or supplemental oxygen; and embracing telehealth as a way to improve accessibility for follow-up visits.

For details, please review the papers published in the November 2021 issue of the journal CHEST^® (2021; 160[5]:1579-1990, e377-e543).

We now await what CMS will do with our recommendations and work for “the right device to the right patient at the right time.”

Acknowledgment: Drs. Gerald Criner, Nicholas Hill, Babak Mohklesi, Timothy Morgenthaler, and Lisa Wolfe assisted with the content.

Use of positive airway pressure (PAP) devices for treatment of sleep apnea was first described in 1981. Subsequent use of PAP devices expanded to treat patients with respiratory failure. While the treatment in this population has rapidly gained widespread use and undoubtedly has reduced morbidity and mortality in these populations, policies governing these prescriptions have not really kept up with the burgeoning need.

In 2020, Drs. Peter Gay and Robert Owens brought together a technical expert panel (TEP) to systematically review the CMS policies with an eye to remove “regulatory barriers” to improve access for these patients with the mantra: “the right device gets to the right patient at the right time.”

The panel focused on “Optimal NIV Medicare Access Promotion (ONMAP),” and members with specific expertise were recruited for five patient groups: Thoracic Restrictive Disorders (TRD), COPD, Central Sleep Apnea (CSA), Hypoventilation Syndromes (HVS), and Obstructive Sleep Apnea (OSA). Each group reviewed the current coverage, outlined the deficiencies, and suggested revisions. Herein, I will briefly highlight each group’s most important points.
 

TRD: The goal for this group was to bring the US standards of care closer to the rest of the world. This group advocates that the start of noninvasive ventilation (NIV) should be substantially earlier, to provide the largest improvement in disease outcome and stability. Other prominent features submitted included arterial blood gases (ABG) to not be the only form of CO₂ measurement allowed; paying for a second device if patients are using NIV continuously; qualification for a BiPAP to include if vital capacity is ≤ 80%; and, to obtain a home mechanical ventilator, a patient must either fail BiPAP or have extreme loss of function, high pressure requirements, or need mouthpiece ventilation.

CSA: The big challenges with this diagnosis related to qualifying coverage language in the current policies, which are confusing for many providers. Additionally, these policies often deny certain PAP devices and/or oxygen therapy. The group proposed: a single definition of CSA; eliminate discussion of hypoventilation; mirror qualifying symptoms, and, continuing coverage, to the same as that for OSA treatment; and remove need for a prior failure of BiPAP without a backup rate (BUR). The group also had specific recommendations for when oxygen therapy should be covered in patients with CSA.

COPD: This group also focused on the oxygen therapy and promoting use of devices with a BUR. Two problematic areas included the requirement that nocturnal oxygen saturation must drop to ≤ 88% for at least 5 cumulative minutes, and, that patients must begin with an S mode device (no BUR) for at least 2 months and can only then be prescribed a device with a BUR if CO₂ fails to drop. The group advocates for the removal of both, the need for a nocturnal oximetry test, and, to “try” an S mode device. The panel advocated giving the prescribing physician discretion in making this determination. The panel also provided recommendations on when a home mechanical ventilator (HMV) should be considered instead of BiPAP therapy.

HVS: Hypoventilation syndromes are a heterogeneous group of disorders with hypercapnia, defined as a Paco₂ ≥45 mm Hg. This panel noted that the current coverage criteria are outdated and fail to recognize the spectrum of disease severity and advances in technology, which often leads to circumvention by prescribing more costly home mechanical ventilators (HMV). Consistent with the TRD group, this panel recommended acceptance of surrogate noninvasive end tidal and transcutaneous Pco₂ and venous blood gases in lieu of arterial blood gases. Additionally, they suggested no longer requiring CO₂ measures while using prescribed oxygen; eliminating the need for a sleep study to avoid delays in care for patients being discharged from the hospital; removing spirometry as a requirement; and no longer a failure of BiPAP without a BUR.

OSA: The initial purpose of examining OSA in this process was to examine when BiPAP should be utilized for treatment; however, it necessitated examination of the entire policy for PAP. The areas that were identified as needing revision included: expansion of the symptom list for patients with OSA; revising the “4 hour rule,” suggesting that 2 hours has been proven to provide benefit; eliminating the need for another sleep study to re-qualify for PAP or supplemental oxygen; and embracing telehealth as a way to improve accessibility for follow-up visits.

For details, please review the papers published in the November 2021 issue of the journal CHEST^® (2021; 160[5]:1579-1990, e377-e543).

We now await what CMS will do with our recommendations and work for “the right device to the right patient at the right time.”

Acknowledgment: Drs. Gerald Criner, Nicholas Hill, Babak Mohklesi, Timothy Morgenthaler, and Lisa Wolfe assisted with the content.

Use of positive airway pressure (PAP) devices for treatment of sleep apnea was first described in 1981. Subsequent use of PAP devices expanded to treat patients with respiratory failure. While the treatment in this population has rapidly gained widespread use and undoubtedly has reduced morbidity and mortality in these populations, policies governing these prescriptions have not really kept up with the burgeoning need.

In 2020, Drs. Peter Gay and Robert Owens brought together a technical expert panel (TEP) to systematically review the CMS policies with an eye to remove “regulatory barriers” to improve access for these patients with the mantra: “the right device gets to the right patient at the right time.”

The panel focused on “Optimal NIV Medicare Access Promotion (ONMAP),” and members with specific expertise were recruited for five patient groups: Thoracic Restrictive Disorders (TRD), COPD, Central Sleep Apnea (CSA), Hypoventilation Syndromes (HVS), and Obstructive Sleep Apnea (OSA). Each group reviewed the current coverage, outlined the deficiencies, and suggested revisions. Herein, I will briefly highlight each group’s most important points.
 

TRD: The goal for this group was to bring the US standards of care closer to the rest of the world. This group advocates that the start of noninvasive ventilation (NIV) should be substantially earlier, to provide the largest improvement in disease outcome and stability. Other prominent features submitted included arterial blood gases (ABG) to not be the only form of CO₂ measurement allowed; paying for a second device if patients are using NIV continuously; qualification for a BiPAP to include if vital capacity is ≤ 80%; and, to obtain a home mechanical ventilator, a patient must either fail BiPAP or have extreme loss of function, high pressure requirements, or need mouthpiece ventilation.

CSA: The big challenges with this diagnosis related to qualifying coverage language in the current policies, which are confusing for many providers. Additionally, these policies often deny certain PAP devices and/or oxygen therapy. The group proposed: a single definition of CSA; eliminate discussion of hypoventilation; mirror qualifying symptoms, and, continuing coverage, to the same as that for OSA treatment; and remove need for a prior failure of BiPAP without a backup rate (BUR). The group also had specific recommendations for when oxygen therapy should be covered in patients with CSA.

COPD: This group also focused on the oxygen therapy and promoting use of devices with a BUR. Two problematic areas included the requirement that nocturnal oxygen saturation must drop to ≤ 88% for at least 5 cumulative minutes, and, that patients must begin with an S mode device (no BUR) for at least 2 months and can only then be prescribed a device with a BUR if CO₂ fails to drop. The group advocates for the removal of both, the need for a nocturnal oximetry test, and, to “try” an S mode device. The panel advocated giving the prescribing physician discretion in making this determination. The panel also provided recommendations on when a home mechanical ventilator (HMV) should be considered instead of BiPAP therapy.

HVS: Hypoventilation syndromes are a heterogeneous group of disorders with hypercapnia, defined as a Paco₂ ≥45 mm Hg. This panel noted that the current coverage criteria are outdated and fail to recognize the spectrum of disease severity and advances in technology, which often leads to circumvention by prescribing more costly home mechanical ventilators (HMV). Consistent with the TRD group, this panel recommended acceptance of surrogate noninvasive end tidal and transcutaneous Pco₂ and venous blood gases in lieu of arterial blood gases. Additionally, they suggested no longer requiring CO₂ measures while using prescribed oxygen; eliminating the need for a sleep study to avoid delays in care for patients being discharged from the hospital; removing spirometry as a requirement; and no longer a failure of BiPAP without a BUR.

OSA: The initial purpose of examining OSA in this process was to examine when BiPAP should be utilized for treatment; however, it necessitated examination of the entire policy for PAP. The areas that were identified as needing revision included: expansion of the symptom list for patients with OSA; revising the “4 hour rule,” suggesting that 2 hours has been proven to provide benefit; eliminating the need for another sleep study to re-qualify for PAP or supplemental oxygen; and embracing telehealth as a way to improve accessibility for follow-up visits.

For details, please review the papers published in the November 2021 issue of the journal CHEST^® (2021; 160[5]:1579-1990, e377-e543).

We now await what CMS will do with our recommendations and work for “the right device to the right patient at the right time.”

Acknowledgment: Drs. Gerald Criner, Nicholas Hill, Babak Mohklesi, Timothy Morgenthaler, and Lisa Wolfe assisted with the content.

Since the onset of the pandemic, the role for corticosteroids (CS) as a therapy for COVID-19 has evolved. Initially, there was reluctance to use oral corticosteroids (OCS) outside of COVID-19-related sepsis or acute respiratory distress syndrome (ARDS). This was in keeping with community-acquired pneumonia (CAP) guidelines (Metlay JP, et al.Am J Respir Crit Care Med. 2019; 200:e45-e67) and reflected concerns that OCS might worsen outcomes in viral pneumonias. At my hospital, the reluctance to use OCS was extended to inhaled corticosteroids (ICS), with early protocols advising cessation in patients with COVID-19.

In fairness, the hesitation to use ICS was short-lived and reflected attempts to provide reasonable guidance during the early pandemic data vacuum. Over time, OCS therapy has gained acceptance as a treatment for moderate-to-severe COVID-19. On top of this, the relationship between COVID-19 and asthma has proved to be complicated. It seemed intuitive that asthmatics would fair worse in the face of a highly transmissible respiratory pathogen. Data on COVID-19 and asthma provide a mixed picture, though. It also appears that the interaction varies by phenotype (Zhu Z, et al. J Allergy Clin Immunol. 2020;146:327-329).

Improvements with OCS and the complicated interaction between COVID-19 and asthma led some to speculate that ICS, the primary treatment for asthma, may actually be protective. There is biologic plausibility to support this concept. Generally, we’ve seen a variety of immunomodulators show efficacy against moderate or severe disease. Specific to ICS, data have shown a down-regulation in COVID-19 gene expression and reduction in proteins required by the virus for cell entry. This includes a reduction in the evil, much maligned ACE-2 receptor (Peters M, et al. Am J Respir Crit Care Med. 2020;202:83-90).

Like much with COVID-19, the initial asthma phenotype and ICS data were observational and hypothesis- generating, at best. More recently, a series of randomized trials has tested the effects of ICS in patients with milder forms of COVID-19. The data are promising and are worth a thorough review by all physicians caring for COVID-19 outside of the hospital.

The STOIC trial (Ramakrishnan S, et al. Lancet Respir Med. 2021;9:763–772) randomized 146 patients to budesonide via dry powder inhaler (DPI), 800 ug twice per day (BID), versus usual care. The primary outcome was clinical deterioration, defined as presentation to acute or emergency care or need for hospitalization. There was a number of secondary outcomes designed to assess time-to-recovery, predominantly by self-report via questionnaires. The results were nothing short of spectacular. There was a significant difference in the primary outcome with a number-needed to treat (NNT) of only 8 to prevent one instance of COVID-19 deterioration. A number of the secondary outcomes reached significance, as well.

The PRINCIPLE trial, only available in preprint form (https://tinyurl.com/mr4cah7j), also randomized patients to budesonide via ICS vs usual care. PRINCIPLE is one of those cool, adaptive platform trials designed to evaluate multiple therapies simultaneously that have gained popularity in the pandemic era. These trials include predefined criteria for success and futility that allow treatments to be added and others to be dropped. The dosage of budesonide was identical to that in STOIC, and, again, it was delivered via DPI. By design, patients were older with co-morbidities, and there were two primary outcomes. The first was a composite of hospitalization and death, and the second was time to recovery.

The PRINCIPLE preprint is only an interim analysis. There were 751 and 1,028 patients who received budesonide and usual care, respectively. Time to recovery was significantly shorter in the budesonide group, but budesonide failed to meet their prespecified criteria for reducing hospitalization/death. The authors noted that the composite outcome of hospitalization or death did not occur at the rates originally anticipated, presumably due to high vaccination rates. This may have led to type II error.

In a third trial published online in November (Clemency BM, et al. JAMA Intern Med. 2021;10.1001/jamainternmed.2021.6759), patients were randomized to 640 micrograms per day of the ICS ciclesonide. Delivery was via metered-dose inhaler (MDI) for a total duration of 30 days. Unlike the STOIC and PRINCIPLE trials, this one wasn’t open label. It was blinded and placebo-controlled. The investigators found no difference in their primary outcome, time to resolution of symptoms. Ciclesonide did reduce the composite secondary outcome of ED visits or hospital admissions. The number needed to treat was 23.

Please indulge me while I overreact. It seems we’ve got a positive signal in all three. In the era of the Omnicron variant and limited health resources, a widely available therapy that curtails symptoms and prevents acute care visits and hospitalizations could have a tremendous impact. It doesn’t require administration in a clinic and, in theory, efficacy shouldn’t be affected by future mutations of the virus.

A more sober look mutes my enthusiasm. First, as the authors of the ciclesonide article note, open-label trials tracking subjective outcomes via self-assessment can be prone to bias. The ciclesonide trial was double-blinded and didn’t find a difference in time to symptom resolution, only the two open-label trials did. Second, the largest study (PRINCIPLE) didn’t show a difference in escalation of care.

Given, they defined “escalation” as hospitalization or death, and vaccines and patient selection (enrolled only outpatients with mild disease) made proving a statistical reduction difficult. However, in the text they state there wasn’t an improvement in “health care services use” either. In essence, the largest trial showed no change in escalation of care, and the trial with the best design did not show reduction in symptoms.

Although three randomized trials are enough for the inevitable meta-analysis that’ll be published soon; don’t expect it to shed much light. Combining data won’t be particularly helpful because the PRINCIPLE trial is larger than the other two combined, so its results will dominate any statistical analysis of combined data. Not to worry though – there are several more ICS COVID-19 trials underway (NCT04355637, NCT04331054, NCT04193878, NCT04330586, NCT04331054, NCT04331470, NCT04355637, NCT04356495, and NCT04381364). Providers will have to decide for themselves whether what we have so far is sufficient to change practice.

Dr. Holley is Program Director, Pulmonary and Critical Care Medicine Fellowship; and Associate Professor of Medicine USU, Walter Reed National Military Medical Center, Bethesda, Maryland. He also serves as Section Editor for Pulmonary Perspectives^®.

Since the onset of the pandemic, the role for corticosteroids (CS) as a therapy for COVID-19 has evolved. Initially, there was reluctance to use oral corticosteroids (OCS) outside of COVID-19-related sepsis or acute respiratory distress syndrome (ARDS). This was in keeping with community-acquired pneumonia (CAP) guidelines (Metlay JP, et al.Am J Respir Crit Care Med. 2019; 200:e45-e67) and reflected concerns that OCS might worsen outcomes in viral pneumonias. At my hospital, the reluctance to use OCS was extended to inhaled corticosteroids (ICS), with early protocols advising cessation in patients with COVID-19.

In fairness, the hesitation to use ICS was short-lived and reflected attempts to provide reasonable guidance during the early pandemic data vacuum. Over time, OCS therapy has gained acceptance as a treatment for moderate-to-severe COVID-19. On top of this, the relationship between COVID-19 and asthma has proved to be complicated. It seemed intuitive that asthmatics would fair worse in the face of a highly transmissible respiratory pathogen. Data on COVID-19 and asthma provide a mixed picture, though. It also appears that the interaction varies by phenotype (Zhu Z, et al. J Allergy Clin Immunol. 2020;146:327-329).

Improvements with OCS and the complicated interaction between COVID-19 and asthma led some to speculate that ICS, the primary treatment for asthma, may actually be protective. There is biologic plausibility to support this concept. Generally, we’ve seen a variety of immunomodulators show efficacy against moderate or severe disease. Specific to ICS, data have shown a down-regulation in COVID-19 gene expression and reduction in proteins required by the virus for cell entry. This includes a reduction in the evil, much maligned ACE-2 receptor (Peters M, et al. Am J Respir Crit Care Med. 2020;202:83-90).

Like much with COVID-19, the initial asthma phenotype and ICS data were observational and hypothesis- generating, at best. More recently, a series of randomized trials has tested the effects of ICS in patients with milder forms of COVID-19. The data are promising and are worth a thorough review by all physicians caring for COVID-19 outside of the hospital.

The STOIC trial (Ramakrishnan S, et al. Lancet Respir Med. 2021;9:763–772) randomized 146 patients to budesonide via dry powder inhaler (DPI), 800 ug twice per day (BID), versus usual care. The primary outcome was clinical deterioration, defined as presentation to acute or emergency care or need for hospitalization. There was a number of secondary outcomes designed to assess time-to-recovery, predominantly by self-report via questionnaires. The results were nothing short of spectacular. There was a significant difference in the primary outcome with a number-needed to treat (NNT) of only 8 to prevent one instance of COVID-19 deterioration. A number of the secondary outcomes reached significance, as well.

The PRINCIPLE trial, only available in preprint form (https://tinyurl.com/mr4cah7j), also randomized patients to budesonide via ICS vs usual care. PRINCIPLE is one of those cool, adaptive platform trials designed to evaluate multiple therapies simultaneously that have gained popularity in the pandemic era. These trials include predefined criteria for success and futility that allow treatments to be added and others to be dropped. The dosage of budesonide was identical to that in STOIC, and, again, it was delivered via DPI. By design, patients were older with co-morbidities, and there were two primary outcomes. The first was a composite of hospitalization and death, and the second was time to recovery.

The PRINCIPLE preprint is only an interim analysis. There were 751 and 1,028 patients who received budesonide and usual care, respectively. Time to recovery was significantly shorter in the budesonide group, but budesonide failed to meet their prespecified criteria for reducing hospitalization/death. The authors noted that the composite outcome of hospitalization or death did not occur at the rates originally anticipated, presumably due to high vaccination rates. This may have led to type II error.

In a third trial published online in November (Clemency BM, et al. JAMA Intern Med. 2021;10.1001/jamainternmed.2021.6759), patients were randomized to 640 micrograms per day of the ICS ciclesonide. Delivery was via metered-dose inhaler (MDI) for a total duration of 30 days. Unlike the STOIC and PRINCIPLE trials, this one wasn’t open label. It was blinded and placebo-controlled. The investigators found no difference in their primary outcome, time to resolution of symptoms. Ciclesonide did reduce the composite secondary outcome of ED visits or hospital admissions. The number needed to treat was 23.

Please indulge me while I overreact. It seems we’ve got a positive signal in all three. In the era of the Omnicron variant and limited health resources, a widely available therapy that curtails symptoms and prevents acute care visits and hospitalizations could have a tremendous impact. It doesn’t require administration in a clinic and, in theory, efficacy shouldn’t be affected by future mutations of the virus.

A more sober look mutes my enthusiasm. First, as the authors of the ciclesonide article note, open-label trials tracking subjective outcomes via self-assessment can be prone to bias. The ciclesonide trial was double-blinded and didn’t find a difference in time to symptom resolution, only the two open-label trials did. Second, the largest study (PRINCIPLE) didn’t show a difference in escalation of care.

Given, they defined “escalation” as hospitalization or death, and vaccines and patient selection (enrolled only outpatients with mild disease) made proving a statistical reduction difficult. However, in the text they state there wasn’t an improvement in “health care services use” either. In essence, the largest trial showed no change in escalation of care, and the trial with the best design did not show reduction in symptoms.

Although three randomized trials are enough for the inevitable meta-analysis that’ll be published soon; don’t expect it to shed much light. Combining data won’t be particularly helpful because the PRINCIPLE trial is larger than the other two combined, so its results will dominate any statistical analysis of combined data. Not to worry though – there are several more ICS COVID-19 trials underway (NCT04355637, NCT04331054, NCT04193878, NCT04330586, NCT04331054, NCT04331470, NCT04355637, NCT04356495, and NCT04381364). Providers will have to decide for themselves whether what we have so far is sufficient to change practice.

Dr. Holley is Program Director, Pulmonary and Critical Care Medicine Fellowship; and Associate Professor of Medicine USU, Walter Reed National Military Medical Center, Bethesda, Maryland. He also serves as Section Editor for Pulmonary Perspectives^®.

Since the onset of the pandemic, the role for corticosteroids (CS) as a therapy for COVID-19 has evolved. Initially, there was reluctance to use oral corticosteroids (OCS) outside of COVID-19-related sepsis or acute respiratory distress syndrome (ARDS). This was in keeping with community-acquired pneumonia (CAP) guidelines (Metlay JP, et al.Am J Respir Crit Care Med. 2019; 200:e45-e67) and reflected concerns that OCS might worsen outcomes in viral pneumonias. At my hospital, the reluctance to use OCS was extended to inhaled corticosteroids (ICS), with early protocols advising cessation in patients with COVID-19.

In fairness, the hesitation to use ICS was short-lived and reflected attempts to provide reasonable guidance during the early pandemic data vacuum. Over time, OCS therapy has gained acceptance as a treatment for moderate-to-severe COVID-19. On top of this, the relationship between COVID-19 and asthma has proved to be complicated. It seemed intuitive that asthmatics would fair worse in the face of a highly transmissible respiratory pathogen. Data on COVID-19 and asthma provide a mixed picture, though. It also appears that the interaction varies by phenotype (Zhu Z, et al. J Allergy Clin Immunol. 2020;146:327-329).

Improvements with OCS and the complicated interaction between COVID-19 and asthma led some to speculate that ICS, the primary treatment for asthma, may actually be protective. There is biologic plausibility to support this concept. Generally, we’ve seen a variety of immunomodulators show efficacy against moderate or severe disease. Specific to ICS, data have shown a down-regulation in COVID-19 gene expression and reduction in proteins required by the virus for cell entry. This includes a reduction in the evil, much maligned ACE-2 receptor (Peters M, et al. Am J Respir Crit Care Med. 2020;202:83-90).

Like much with COVID-19, the initial asthma phenotype and ICS data were observational and hypothesis- generating, at best. More recently, a series of randomized trials has tested the effects of ICS in patients with milder forms of COVID-19. The data are promising and are worth a thorough review by all physicians caring for COVID-19 outside of the hospital.

The STOIC trial (Ramakrishnan S, et al. Lancet Respir Med. 2021;9:763–772) randomized 146 patients to budesonide via dry powder inhaler (DPI), 800 ug twice per day (BID), versus usual care. The primary outcome was clinical deterioration, defined as presentation to acute or emergency care or need for hospitalization. There was a number of secondary outcomes designed to assess time-to-recovery, predominantly by self-report via questionnaires. The results were nothing short of spectacular. There was a significant difference in the primary outcome with a number-needed to treat (NNT) of only 8 to prevent one instance of COVID-19 deterioration. A number of the secondary outcomes reached significance, as well.

The PRINCIPLE trial, only available in preprint form (https://tinyurl.com/mr4cah7j), also randomized patients to budesonide via ICS vs usual care. PRINCIPLE is one of those cool, adaptive platform trials designed to evaluate multiple therapies simultaneously that have gained popularity in the pandemic era. These trials include predefined criteria for success and futility that allow treatments to be added and others to be dropped. The dosage of budesonide was identical to that in STOIC, and, again, it was delivered via DPI. By design, patients were older with co-morbidities, and there were two primary outcomes. The first was a composite of hospitalization and death, and the second was time to recovery.

The PRINCIPLE preprint is only an interim analysis. There were 751 and 1,028 patients who received budesonide and usual care, respectively. Time to recovery was significantly shorter in the budesonide group, but budesonide failed to meet their prespecified criteria for reducing hospitalization/death. The authors noted that the composite outcome of hospitalization or death did not occur at the rates originally anticipated, presumably due to high vaccination rates. This may have led to type II error.

In a third trial published online in November (Clemency BM, et al. JAMA Intern Med. 2021;10.1001/jamainternmed.2021.6759), patients were randomized to 640 micrograms per day of the ICS ciclesonide. Delivery was via metered-dose inhaler (MDI) for a total duration of 30 days. Unlike the STOIC and PRINCIPLE trials, this one wasn’t open label. It was blinded and placebo-controlled. The investigators found no difference in their primary outcome, time to resolution of symptoms. Ciclesonide did reduce the composite secondary outcome of ED visits or hospital admissions. The number needed to treat was 23.

Please indulge me while I overreact. It seems we’ve got a positive signal in all three. In the era of the Omnicron variant and limited health resources, a widely available therapy that curtails symptoms and prevents acute care visits and hospitalizations could have a tremendous impact. It doesn’t require administration in a clinic and, in theory, efficacy shouldn’t be affected by future mutations of the virus.

A more sober look mutes my enthusiasm. First, as the authors of the ciclesonide article note, open-label trials tracking subjective outcomes via self-assessment can be prone to bias. The ciclesonide trial was double-blinded and didn’t find a difference in time to symptom resolution, only the two open-label trials did. Second, the largest study (PRINCIPLE) didn’t show a difference in escalation of care.

Given, they defined “escalation” as hospitalization or death, and vaccines and patient selection (enrolled only outpatients with mild disease) made proving a statistical reduction difficult. However, in the text they state there wasn’t an improvement in “health care services use” either. In essence, the largest trial showed no change in escalation of care, and the trial with the best design did not show reduction in symptoms.

Although three randomized trials are enough for the inevitable meta-analysis that’ll be published soon; don’t expect it to shed much light. Combining data won’t be particularly helpful because the PRINCIPLE trial is larger than the other two combined, so its results will dominate any statistical analysis of combined data. Not to worry though – there are several more ICS COVID-19 trials underway (NCT04355637, NCT04331054, NCT04193878, NCT04330586, NCT04331054, NCT04331470, NCT04355637, NCT04356495, and NCT04381364). Providers will have to decide for themselves whether what we have so far is sufficient to change practice.

Dr. Holley is Program Director, Pulmonary and Critical Care Medicine Fellowship; and Associate Professor of Medicine USU, Walter Reed National Military Medical Center, Bethesda, Maryland. He also serves as Section Editor for Pulmonary Perspectives^®.

Younger and older patients with severe chronic obstructive pulmonary disease have similar pulmonary and physical health limitations, based on data from 1,058 adults.

Although chronic obstructive pulmonary disease (COPD) generally appears in older patients, the prevalence among adults aged 45-55 years was 6.5% in 2014-2015, wrote Rosanne J.H.C.G. Beijers, PhD, of Maastricht (the Netherlands) University Medical Center, and colleagues. However, data on the early-onset COPD phenotype are limited. In particular, the extent to which younger patients with early-onset severe COPD experienced the same physical and mental health problems as older patients with similar degree of airflow limitation has not been examined, they said.

In a study published in Clinical Nutrition, the researchers analyzed data from adults with COPD who were referred for pulmonary rehabilitation at a single center between July 2013 and August 2018. Severe disease was defined as FEV1< 50%, and early onset was defined as younger than 55 years. The mean age difference between older and younger patient groups was 15.8 years.

The study population included 79 individuals with early-onset severe disease, 54 with early-onset mild to moderate disease, 158 older adults with severe disease, and 103 older adults with mild to moderate disease. The researchers compared disease markers including body composition, physical performance, and mental health between the groups. A significantly greater proportion of the early-onset group were women, compared to the older group (64% vs. 44%).

In comparing early-onset and older patients with severe COPD, the researchers found that clinical characteristics were similar for body composition, skeletal muscle index, fat percentage, and bone mineral content, and for physical performance factors including the percent predicted maximal work capacity (Wmax), 6-minute walk test, and isokinetic strength. However, a higher prevalence of depression appeared in the early-onset severe-disease patients, compared with the older severe-disease patients (51.9% vs. 32.7%; P = .029).

Although the prevalence of depression was not based on a clinical diagnosis, this finding should prompt health care professionals to pay more attention to psychosocial and emotional well-being in early-onset severe COPD patients, the researchers noted.

In comparing early-onset severe-disease patients and early-onset patients with mild to moderate disease, patients with early-onset severe COPD had significantly lower exercise performance, based on a 6-minute walk test and percent predicted Wmax. However, body composition and isokinetic muscle strength were not significantly different between both early-onset groups.

The findings were limited by several factors including the relatively small number of early-onset patients and the lack of data on whether older patients were diagnosed with severe COPD at a younger age, and more research using age and lung function at the time of diagnosis is needed, the researchers noted. However, the results highlight the importance of early identification of patients at risk for early-onset severe COPD, they said. “Within these individuals at risk, special attention should also be paid to the development of extrapulmonary disease manifestations such as exercise limitations, impaired body composition, and psychological and emotional problems,” the researchers said. “Subsequently, intervention strategies need to be applied that not only focus on the regular advice of quitting smoking but also include decreasing the exposure to air pollutants and promoting a healthy lifestyle including physical activity and a healthy diet,” they added.

The study received no outside funding. Lead author Dr. Beijers had no financial conflicts to disclose.

Younger and older patients with severe chronic obstructive pulmonary disease have similar pulmonary and physical health limitations, based on data from 1,058 adults.

Although chronic obstructive pulmonary disease (COPD) generally appears in older patients, the prevalence among adults aged 45-55 years was 6.5% in 2014-2015, wrote Rosanne J.H.C.G. Beijers, PhD, of Maastricht (the Netherlands) University Medical Center, and colleagues. However, data on the early-onset COPD phenotype are limited. In particular, the extent to which younger patients with early-onset severe COPD experienced the same physical and mental health problems as older patients with similar degree of airflow limitation has not been examined, they said.

In a study published in Clinical Nutrition, the researchers analyzed data from adults with COPD who were referred for pulmonary rehabilitation at a single center between July 2013 and August 2018. Severe disease was defined as FEV1< 50%, and early onset was defined as younger than 55 years. The mean age difference between older and younger patient groups was 15.8 years.

The study population included 79 individuals with early-onset severe disease, 54 with early-onset mild to moderate disease, 158 older adults with severe disease, and 103 older adults with mild to moderate disease. The researchers compared disease markers including body composition, physical performance, and mental health between the groups. A significantly greater proportion of the early-onset group were women, compared to the older group (64% vs. 44%).

In comparing early-onset and older patients with severe COPD, the researchers found that clinical characteristics were similar for body composition, skeletal muscle index, fat percentage, and bone mineral content, and for physical performance factors including the percent predicted maximal work capacity (Wmax), 6-minute walk test, and isokinetic strength. However, a higher prevalence of depression appeared in the early-onset severe-disease patients, compared with the older severe-disease patients (51.9% vs. 32.7%; P = .029).

Although the prevalence of depression was not based on a clinical diagnosis, this finding should prompt health care professionals to pay more attention to psychosocial and emotional well-being in early-onset severe COPD patients, the researchers noted.

In comparing early-onset severe-disease patients and early-onset patients with mild to moderate disease, patients with early-onset severe COPD had significantly lower exercise performance, based on a 6-minute walk test and percent predicted Wmax. However, body composition and isokinetic muscle strength were not significantly different between both early-onset groups.

The findings were limited by several factors including the relatively small number of early-onset patients and the lack of data on whether older patients were diagnosed with severe COPD at a younger age, and more research using age and lung function at the time of diagnosis is needed, the researchers noted. However, the results highlight the importance of early identification of patients at risk for early-onset severe COPD, they said. “Within these individuals at risk, special attention should also be paid to the development of extrapulmonary disease manifestations such as exercise limitations, impaired body composition, and psychological and emotional problems,” the researchers said. “Subsequently, intervention strategies need to be applied that not only focus on the regular advice of quitting smoking but also include decreasing the exposure to air pollutants and promoting a healthy lifestyle including physical activity and a healthy diet,” they added.

The study received no outside funding. Lead author Dr. Beijers had no financial conflicts to disclose.

Younger and older patients with severe chronic obstructive pulmonary disease have similar pulmonary and physical health limitations, based on data from 1,058 adults.

Although chronic obstructive pulmonary disease (COPD) generally appears in older patients, the prevalence among adults aged 45-55 years was 6.5% in 2014-2015, wrote Rosanne J.H.C.G. Beijers, PhD, of Maastricht (the Netherlands) University Medical Center, and colleagues. However, data on the early-onset COPD phenotype are limited. In particular, the extent to which younger patients with early-onset severe COPD experienced the same physical and mental health problems as older patients with similar degree of airflow limitation has not been examined, they said.

In a study published in Clinical Nutrition, the researchers analyzed data from adults with COPD who were referred for pulmonary rehabilitation at a single center between July 2013 and August 2018. Severe disease was defined as FEV1< 50%, and early onset was defined as younger than 55 years. The mean age difference between older and younger patient groups was 15.8 years.

The study population included 79 individuals with early-onset severe disease, 54 with early-onset mild to moderate disease, 158 older adults with severe disease, and 103 older adults with mild to moderate disease. The researchers compared disease markers including body composition, physical performance, and mental health between the groups. A significantly greater proportion of the early-onset group were women, compared to the older group (64% vs. 44%).

In comparing early-onset and older patients with severe COPD, the researchers found that clinical characteristics were similar for body composition, skeletal muscle index, fat percentage, and bone mineral content, and for physical performance factors including the percent predicted maximal work capacity (Wmax), 6-minute walk test, and isokinetic strength. However, a higher prevalence of depression appeared in the early-onset severe-disease patients, compared with the older severe-disease patients (51.9% vs. 32.7%; P = .029).

Although the prevalence of depression was not based on a clinical diagnosis, this finding should prompt health care professionals to pay more attention to psychosocial and emotional well-being in early-onset severe COPD patients, the researchers noted.

In comparing early-onset severe-disease patients and early-onset patients with mild to moderate disease, patients with early-onset severe COPD had significantly lower exercise performance, based on a 6-minute walk test and percent predicted Wmax. However, body composition and isokinetic muscle strength were not significantly different between both early-onset groups.

The findings were limited by several factors including the relatively small number of early-onset patients and the lack of data on whether older patients were diagnosed with severe COPD at a younger age, and more research using age and lung function at the time of diagnosis is needed, the researchers noted. However, the results highlight the importance of early identification of patients at risk for early-onset severe COPD, they said. “Within these individuals at risk, special attention should also be paid to the development of extrapulmonary disease manifestations such as exercise limitations, impaired body composition, and psychological and emotional problems,” the researchers said. “Subsequently, intervention strategies need to be applied that not only focus on the regular advice of quitting smoking but also include decreasing the exposure to air pollutants and promoting a healthy lifestyle including physical activity and a healthy diet,” they added.

The study received no outside funding. Lead author Dr. Beijers had no financial conflicts to disclose.

In a specialty clinic, dupilumab (Dupixent) injections significantly improved symptoms for patients with chronic rhinosinusitis with nasal polyps, based on provisional data from more than 100 adults.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a significant burden among working-age adults. Symptom control remains a challenge for many of these patients, and the cost in lost productivity and health care consumption can be substantial, write Rik J.L. van der Lans, MD, of the University of Amsterdam, and colleagues.

Dupilumab, a biologic that targets components of the type 2 inflammatory pathway, represents a new option that has shown effectiveness in clinical trials for regulatory approval, they said.

A new observational study tests dupilumab in patients who met criteria for biological treatment proposed in a recent major systematic review. The findings were published in the journal Allergy.

In the study, the researchers identified 131 adults older than 18 years (mean age 51.7) with CRSwNP treated at a single tertiary care center. Participants received 300 mg of dupilumab subcutaneous injection every 2 weeks for at least 12 weeks.

The primary outcomes were scores on several measures, including the SinoNasal Outcome Test-22 (SNOT-22, scale of 0-110), the bilateral Nasal Polyp Score (NPS, scale of 0-8), and the Sniffin’ Sticks-12 identification test (SSIT-12, scale of 0-6 anosmia, 7-10 hyposmia, 11-12 normosmia).

The mean scores on all three outcomes improved significantly from baseline to both 24 weeks and 48 weeks. Scores on the SNOT-22 improved from 52.4 at baseline to 18.5 and 16.8 at weeks 24 and 48, respectively. NPS improved from 5.4 at baseline to 1.6 and 1.0, respectively. SSIT-12 scores improved from 3.6 at baseline to 7.3 and 8.3, respectively.

At baseline, 95.8% of the patients had uncontrolled chronic rhinosinusitis, but at 24 and 48 weeks, respectively, 24.3% and 6.2% were uncontrolled.

Approximately half of the patients experienced treatment-emergent adverse events, but these were “mild and decreased in occurrence and intensity throughout treatment,” the researchers say.

For patients with a strong response, the researchers also tested an extension of the interval between doses to 4 weeks and 6 weeks, in a provisional indication of continued established control at these timepoints.

The study findings were limited by several factors, including the potential for selection bias, and data from only the first patient cohort, the researchers noted. However, the results were strengthened by the real-life context, standardized indications, and long-term follow up for almost a year, they said.

More research is needed on nonacademic patient cohorts, but the current data confirm the effectiveness of dupilumab as an add-on for difficult-to-treat CRSwNP, they concluded. The findings also validate the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2020) inclusion criteria for biologic treatment, they said.

The new study is important because of the need for verification of results from randomized controlled trials using real-world data, Dr. Van der Lans told this news organization.

“For example, differences in treatment efficacy might result from differing indication criteria, and the inclusion/exclusion criteria in the RCTs might have excluded patients one would encounter in daily practice,” he said. “With our prospective observational cohort, we are seeking to verify efficacy, monitor pharmacovigilance, and evaluate and advance the indication criteria and positioning of biologicals registered for CRSwNP, such as dupilumab.”

These cross-sectional results suggest dupilumab is more effective in preventing possibly harmful escape treatments, such as oral corticosteroids and/or surgery, than reported by the registration trials.

“Additionally, it appears possible to maintain established CRS-control during response-dependent, stepwise, interdose interval prolongation of up to 6 weeks, which is officially an off-label dosing interval,” he said. “This would greatly benefit patients’ treatment burden and direct costs,” he said. However, both findings require corroboration by anticipated longitudinal results in 2022, he noted.

The key message for clinicians in practice: “Biologicals like dupilumab are a potent and promising treatment for severe CRSwNP when conventional medical and surgical therapy fails,” he emphasized.

Looking ahead, important research objectives include head-on comparison studies of the diverse biological agents, establishing biomarkers to guide preferential therapy, and evaluating the economics of biologics compared with conventional therapy, Dr. Van der Lans added. Such research is vital not only for improving patient-centered care but to sustain the use of biologicals in a health-economic perspective.

One of the greatest criticisms of biologic therapy for CRSwNP is cost, particularly in a setting of ever-increasing health care costs. A recent review noted the average cost per year is greater than $30,000.
 

Real-life study verifies effectiveness

“As the authors pointed out, this is a real-life, prospective observational cohort with a decently large size, evaluating the therapeutic efficacy of add-on dupilumab,” said Seong H. Cho, MD, of the University of South Florida, Tampa, in an interview.

“Dupilumab is the first FDA-approved biologic to treat severe chronic rhinosinusitis with nasal polyps based on two phase 3 clinical trials,” said Dr. Cho, who was not involved with the study. “It has been more than 2 years since dupilumab was approved for severe CRSwNP by the FDA and EMA. This real-life, prospective, observational study with a decent size verified the efficacy of dupilumab as an add-on treatment when used with a proper indication such as EPOS2020 indication criteria.

“I am not surprised by the efficacy of dupilumab on severe CRSwNP, based on my clinical experience. My clinical observation is similar to the results of this study. This study verifies that dupilumab is highly efficacious in treating refractory and severe CRSwNP in a real-life setting by improving all subjective and objective clinical outcomes such as SNOT-22, NPS, and smell test score,” he said. The study also confirms that a stepwise, interdose interval prolongation from every 2-4 weeks for CRSwNP patients with good response should be a consideration for clinical practice, he added. 

The cost-effectiveness of dupilumab is the main barrier to more consistent use, Dr. Cho said. “There is no evidence that dupilumab can change the course of the disease, and we don’t know how long patients need to be on this drug. Therefore, nasal polyps need to be refractory and severe enough to use dupilumab and other biologics,” he explained.

Consequently, proper indication criteria, such as the EPOS2020 indication criteria for biologics, should be established before initiating dupilumab, Dr. Cho noted.

“Generally, endoscopic sinus surgery would be preferred in sinus-surgery naive CRSwNP patients, unless surgery is contraindicated or refused by patients because of cost-effectiveness rather than the superior efficacy,” he said. “If surgery fails, then dupilumab can be considered. In addition, proper evaluation of nasal polyp severity would be important.”

“One should establish an objective NPS by endoscopic exam before initiation of dupilumab. This baseline score would be an important marker to assess the efficacy of dupilumab in the course of treatment.”

Monitoring of the NPS together with the patient’s symptom improvement would be essential to implementing a stepwise, interdose interval prolongation to reduce the cost, he emphasized. 

“The most crucial additional research is establishing suitable biomarkers for the response of dupilumab and other biologics,” said Dr. Cho. “Overall, the performance of dupilumab seems to be good. But there are patients unresponsive to dupilumab, even more to other recently FDA-approved biologics for CRSwNP.”

Blood eosinophils and exhaled nitric oxide can be a good biomarker for type 2 asthma, Dr. Cho added. “Still, there is no evidence that these biomarkers are decent for CRSwNP, even though CRSwNP is mostly considered as type 2 disease. Therefore, it would be essential to find promising biomarkers for severe CRSwNP.”

Dr. Van der Lans disclosed serving as a consultant for GlaxoSmithKline, and several coauthors disclosed relationships with companies including Sanofi and Novartis. The patient registry from which the study population was drawn is cofunded by Sanofi and Novartis. Dr. Cho has disclosed no relevant financial relationships.

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

In a specialty clinic, dupilumab (Dupixent) injections significantly improved symptoms for patients with chronic rhinosinusitis with nasal polyps, based on provisional data from more than 100 adults.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a significant burden among working-age adults. Symptom control remains a challenge for many of these patients, and the cost in lost productivity and health care consumption can be substantial, write Rik J.L. van der Lans, MD, of the University of Amsterdam, and colleagues.

Dupilumab, a biologic that targets components of the type 2 inflammatory pathway, represents a new option that has shown effectiveness in clinical trials for regulatory approval, they said.

A new observational study tests dupilumab in patients who met criteria for biological treatment proposed in a recent major systematic review. The findings were published in the journal Allergy.

In the study, the researchers identified 131 adults older than 18 years (mean age 51.7) with CRSwNP treated at a single tertiary care center. Participants received 300 mg of dupilumab subcutaneous injection every 2 weeks for at least 12 weeks.

The primary outcomes were scores on several measures, including the SinoNasal Outcome Test-22 (SNOT-22, scale of 0-110), the bilateral Nasal Polyp Score (NPS, scale of 0-8), and the Sniffin’ Sticks-12 identification test (SSIT-12, scale of 0-6 anosmia, 7-10 hyposmia, 11-12 normosmia).

The mean scores on all three outcomes improved significantly from baseline to both 24 weeks and 48 weeks. Scores on the SNOT-22 improved from 52.4 at baseline to 18.5 and 16.8 at weeks 24 and 48, respectively. NPS improved from 5.4 at baseline to 1.6 and 1.0, respectively. SSIT-12 scores improved from 3.6 at baseline to 7.3 and 8.3, respectively.

At baseline, 95.8% of the patients had uncontrolled chronic rhinosinusitis, but at 24 and 48 weeks, respectively, 24.3% and 6.2% were uncontrolled.

Approximately half of the patients experienced treatment-emergent adverse events, but these were “mild and decreased in occurrence and intensity throughout treatment,” the researchers say.

For patients with a strong response, the researchers also tested an extension of the interval between doses to 4 weeks and 6 weeks, in a provisional indication of continued established control at these timepoints.

The study findings were limited by several factors, including the potential for selection bias, and data from only the first patient cohort, the researchers noted. However, the results were strengthened by the real-life context, standardized indications, and long-term follow up for almost a year, they said.

More research is needed on nonacademic patient cohorts, but the current data confirm the effectiveness of dupilumab as an add-on for difficult-to-treat CRSwNP, they concluded. The findings also validate the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2020) inclusion criteria for biologic treatment, they said.

The new study is important because of the need for verification of results from randomized controlled trials using real-world data, Dr. Van der Lans told this news organization.

“For example, differences in treatment efficacy might result from differing indication criteria, and the inclusion/exclusion criteria in the RCTs might have excluded patients one would encounter in daily practice,” he said. “With our prospective observational cohort, we are seeking to verify efficacy, monitor pharmacovigilance, and evaluate and advance the indication criteria and positioning of biologicals registered for CRSwNP, such as dupilumab.”

These cross-sectional results suggest dupilumab is more effective in preventing possibly harmful escape treatments, such as oral corticosteroids and/or surgery, than reported by the registration trials.

“Additionally, it appears possible to maintain established CRS-control during response-dependent, stepwise, interdose interval prolongation of up to 6 weeks, which is officially an off-label dosing interval,” he said. “This would greatly benefit patients’ treatment burden and direct costs,” he said. However, both findings require corroboration by anticipated longitudinal results in 2022, he noted.

The key message for clinicians in practice: “Biologicals like dupilumab are a potent and promising treatment for severe CRSwNP when conventional medical and surgical therapy fails,” he emphasized.

Looking ahead, important research objectives include head-on comparison studies of the diverse biological agents, establishing biomarkers to guide preferential therapy, and evaluating the economics of biologics compared with conventional therapy, Dr. Van der Lans added. Such research is vital not only for improving patient-centered care but to sustain the use of biologicals in a health-economic perspective.

One of the greatest criticisms of biologic therapy for CRSwNP is cost, particularly in a setting of ever-increasing health care costs. A recent review noted the average cost per year is greater than $30,000.
 

Real-life study verifies effectiveness

“As the authors pointed out, this is a real-life, prospective observational cohort with a decently large size, evaluating the therapeutic efficacy of add-on dupilumab,” said Seong H. Cho, MD, of the University of South Florida, Tampa, in an interview.

“Dupilumab is the first FDA-approved biologic to treat severe chronic rhinosinusitis with nasal polyps based on two phase 3 clinical trials,” said Dr. Cho, who was not involved with the study. “It has been more than 2 years since dupilumab was approved for severe CRSwNP by the FDA and EMA. This real-life, prospective, observational study with a decent size verified the efficacy of dupilumab as an add-on treatment when used with a proper indication such as EPOS2020 indication criteria.

“I am not surprised by the efficacy of dupilumab on severe CRSwNP, based on my clinical experience. My clinical observation is similar to the results of this study. This study verifies that dupilumab is highly efficacious in treating refractory and severe CRSwNP in a real-life setting by improving all subjective and objective clinical outcomes such as SNOT-22, NPS, and smell test score,” he said. The study also confirms that a stepwise, interdose interval prolongation from every 2-4 weeks for CRSwNP patients with good response should be a consideration for clinical practice, he added. 

The cost-effectiveness of dupilumab is the main barrier to more consistent use, Dr. Cho said. “There is no evidence that dupilumab can change the course of the disease, and we don’t know how long patients need to be on this drug. Therefore, nasal polyps need to be refractory and severe enough to use dupilumab and other biologics,” he explained.

Consequently, proper indication criteria, such as the EPOS2020 indication criteria for biologics, should be established before initiating dupilumab, Dr. Cho noted.

“Generally, endoscopic sinus surgery would be preferred in sinus-surgery naive CRSwNP patients, unless surgery is contraindicated or refused by patients because of cost-effectiveness rather than the superior efficacy,” he said. “If surgery fails, then dupilumab can be considered. In addition, proper evaluation of nasal polyp severity would be important.”

“One should establish an objective NPS by endoscopic exam before initiation of dupilumab. This baseline score would be an important marker to assess the efficacy of dupilumab in the course of treatment.”

Monitoring of the NPS together with the patient’s symptom improvement would be essential to implementing a stepwise, interdose interval prolongation to reduce the cost, he emphasized. 

“The most crucial additional research is establishing suitable biomarkers for the response of dupilumab and other biologics,” said Dr. Cho. “Overall, the performance of dupilumab seems to be good. But there are patients unresponsive to dupilumab, even more to other recently FDA-approved biologics for CRSwNP.”

Blood eosinophils and exhaled nitric oxide can be a good biomarker for type 2 asthma, Dr. Cho added. “Still, there is no evidence that these biomarkers are decent for CRSwNP, even though CRSwNP is mostly considered as type 2 disease. Therefore, it would be essential to find promising biomarkers for severe CRSwNP.”

Dr. Van der Lans disclosed serving as a consultant for GlaxoSmithKline, and several coauthors disclosed relationships with companies including Sanofi and Novartis. The patient registry from which the study population was drawn is cofunded by Sanofi and Novartis. Dr. Cho has disclosed no relevant financial relationships.

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

In a specialty clinic, dupilumab (Dupixent) injections significantly improved symptoms for patients with chronic rhinosinusitis with nasal polyps, based on provisional data from more than 100 adults.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a significant burden among working-age adults. Symptom control remains a challenge for many of these patients, and the cost in lost productivity and health care consumption can be substantial, write Rik J.L. van der Lans, MD, of the University of Amsterdam, and colleagues.

Dupilumab, a biologic that targets components of the type 2 inflammatory pathway, represents a new option that has shown effectiveness in clinical trials for regulatory approval, they said.

A new observational study tests dupilumab in patients who met criteria for biological treatment proposed in a recent major systematic review. The findings were published in the journal Allergy.

In the study, the researchers identified 131 adults older than 18 years (mean age 51.7) with CRSwNP treated at a single tertiary care center. Participants received 300 mg of dupilumab subcutaneous injection every 2 weeks for at least 12 weeks.

The primary outcomes were scores on several measures, including the SinoNasal Outcome Test-22 (SNOT-22, scale of 0-110), the bilateral Nasal Polyp Score (NPS, scale of 0-8), and the Sniffin’ Sticks-12 identification test (SSIT-12, scale of 0-6 anosmia, 7-10 hyposmia, 11-12 normosmia).

The mean scores on all three outcomes improved significantly from baseline to both 24 weeks and 48 weeks. Scores on the SNOT-22 improved from 52.4 at baseline to 18.5 and 16.8 at weeks 24 and 48, respectively. NPS improved from 5.4 at baseline to 1.6 and 1.0, respectively. SSIT-12 scores improved from 3.6 at baseline to 7.3 and 8.3, respectively.

At baseline, 95.8% of the patients had uncontrolled chronic rhinosinusitis, but at 24 and 48 weeks, respectively, 24.3% and 6.2% were uncontrolled.

Approximately half of the patients experienced treatment-emergent adverse events, but these were “mild and decreased in occurrence and intensity throughout treatment,” the researchers say.

For patients with a strong response, the researchers also tested an extension of the interval between doses to 4 weeks and 6 weeks, in a provisional indication of continued established control at these timepoints.

The study findings were limited by several factors, including the potential for selection bias, and data from only the first patient cohort, the researchers noted. However, the results were strengthened by the real-life context, standardized indications, and long-term follow up for almost a year, they said.

More research is needed on nonacademic patient cohorts, but the current data confirm the effectiveness of dupilumab as an add-on for difficult-to-treat CRSwNP, they concluded. The findings also validate the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2020) inclusion criteria for biologic treatment, they said.

The new study is important because of the need for verification of results from randomized controlled trials using real-world data, Dr. Van der Lans told this news organization.

“For example, differences in treatment efficacy might result from differing indication criteria, and the inclusion/exclusion criteria in the RCTs might have excluded patients one would encounter in daily practice,” he said. “With our prospective observational cohort, we are seeking to verify efficacy, monitor pharmacovigilance, and evaluate and advance the indication criteria and positioning of biologicals registered for CRSwNP, such as dupilumab.”

These cross-sectional results suggest dupilumab is more effective in preventing possibly harmful escape treatments, such as oral corticosteroids and/or surgery, than reported by the registration trials.

“Additionally, it appears possible to maintain established CRS-control during response-dependent, stepwise, interdose interval prolongation of up to 6 weeks, which is officially an off-label dosing interval,” he said. “This would greatly benefit patients’ treatment burden and direct costs,” he said. However, both findings require corroboration by anticipated longitudinal results in 2022, he noted.

The key message for clinicians in practice: “Biologicals like dupilumab are a potent and promising treatment for severe CRSwNP when conventional medical and surgical therapy fails,” he emphasized.

Looking ahead, important research objectives include head-on comparison studies of the diverse biological agents, establishing biomarkers to guide preferential therapy, and evaluating the economics of biologics compared with conventional therapy, Dr. Van der Lans added. Such research is vital not only for improving patient-centered care but to sustain the use of biologicals in a health-economic perspective.

One of the greatest criticisms of biologic therapy for CRSwNP is cost, particularly in a setting of ever-increasing health care costs. A recent review noted the average cost per year is greater than $30,000.
 

Real-life study verifies effectiveness

“As the authors pointed out, this is a real-life, prospective observational cohort with a decently large size, evaluating the therapeutic efficacy of add-on dupilumab,” said Seong H. Cho, MD, of the University of South Florida, Tampa, in an interview.

“Dupilumab is the first FDA-approved biologic to treat severe chronic rhinosinusitis with nasal polyps based on two phase 3 clinical trials,” said Dr. Cho, who was not involved with the study. “It has been more than 2 years since dupilumab was approved for severe CRSwNP by the FDA and EMA. This real-life, prospective, observational study with a decent size verified the efficacy of dupilumab as an add-on treatment when used with a proper indication such as EPOS2020 indication criteria.

“I am not surprised by the efficacy of dupilumab on severe CRSwNP, based on my clinical experience. My clinical observation is similar to the results of this study. This study verifies that dupilumab is highly efficacious in treating refractory and severe CRSwNP in a real-life setting by improving all subjective and objective clinical outcomes such as SNOT-22, NPS, and smell test score,” he said. The study also confirms that a stepwise, interdose interval prolongation from every 2-4 weeks for CRSwNP patients with good response should be a consideration for clinical practice, he added. 

The cost-effectiveness of dupilumab is the main barrier to more consistent use, Dr. Cho said. “There is no evidence that dupilumab can change the course of the disease, and we don’t know how long patients need to be on this drug. Therefore, nasal polyps need to be refractory and severe enough to use dupilumab and other biologics,” he explained.

Consequently, proper indication criteria, such as the EPOS2020 indication criteria for biologics, should be established before initiating dupilumab, Dr. Cho noted.

“Generally, endoscopic sinus surgery would be preferred in sinus-surgery naive CRSwNP patients, unless surgery is contraindicated or refused by patients because of cost-effectiveness rather than the superior efficacy,” he said. “If surgery fails, then dupilumab can be considered. In addition, proper evaluation of nasal polyp severity would be important.”

“One should establish an objective NPS by endoscopic exam before initiation of dupilumab. This baseline score would be an important marker to assess the efficacy of dupilumab in the course of treatment.”

Monitoring of the NPS together with the patient’s symptom improvement would be essential to implementing a stepwise, interdose interval prolongation to reduce the cost, he emphasized. 

“The most crucial additional research is establishing suitable biomarkers for the response of dupilumab and other biologics,” said Dr. Cho. “Overall, the performance of dupilumab seems to be good. But there are patients unresponsive to dupilumab, even more to other recently FDA-approved biologics for CRSwNP.”

Blood eosinophils and exhaled nitric oxide can be a good biomarker for type 2 asthma, Dr. Cho added. “Still, there is no evidence that these biomarkers are decent for CRSwNP, even though CRSwNP is mostly considered as type 2 disease. Therefore, it would be essential to find promising biomarkers for severe CRSwNP.”

Dr. Van der Lans disclosed serving as a consultant for GlaxoSmithKline, and several coauthors disclosed relationships with companies including Sanofi and Novartis. The patient registry from which the study population was drawn is cofunded by Sanofi and Novartis. Dr. Cho has disclosed no relevant financial relationships.

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

Sepsis is an alarmingly common cause behind ICU admissions in patients with multiple sclerosis (MS), a retrospective, population-based cohort study indicates.

Furthermore, it contributes to a disproportionately high percentage of the short-term mortality risk among patients with MS admitted to the ICU, findings also show. Short-term mortality risk was defined in the study as a combination of in-hospital death or discharge to hospice.

“We found that the risk of short-term mortality in critically ill patients with MS is four times higher among those with sepsis ... so sepsis appears to be comparatively more lethal among patients with MS than in the general population,” Lavi Oud, MD, professor of medicine, Texas Tech University HSC at the Permian Basin, Odessa, said in an email.

“[Although] the specific mechanisms underlying the markedly higher risk of sepsis among patients with MS compared to the general population remain to be fully elucidated ... it’s thought that the risk may stem from the dysfunction of the immune system in these patients related to MS itself and to the potentially adverse effect of the immunomodulating therapy we use in these patients,” he added.

The study was published online Jan. 11 in the Journal of Critical Care.
 

Sepsis rates

The Texas Inpatient Public Use Data File was used to identify adults with a diagnosis of MS admitted to the hospital between 2010 and 2017. Among the 19,837 patients with MS admitted to the ICU during the study interval, almost one-third (31.5%) had sepsis, investigators report. “The rate of sepsis among ICU admissions increased with age, ranging from 20.8% among those aged 18-44 to 39.4% among those aged 65 years or older,” investigators note.

The most common site of infection among MS patients admitted to the ICU were urinary in nature (65.2%), followed by respiratory (36.1%). A smaller proportion of infections (7.6%) involved the skin and soft tissues, researchers note. A full one-quarter of patients developed septic shock in response to their infection while the length of stay among patients with sepsis (mean of 10.9 days) was substantially longer than it was for those without sepsis (mean of 5.6 days), they observe.

At a mean total hospital cost of $121,797 for each ICU patient with sepsis, the cost of caring for each patient was nearly twofold higher than the mean total cost of taking care of ICU patients without sepsis (mean total cost, $65,179). On adjusted analysis, sepsis was associated with a 42.7% (95% confidence interval, 38.9-46.5; P < .0001) longer length of hospital stay and a 26.2% (95% CI, 23.1-29.1; P < .0001) higher total hospital cost compared with patients without sepsis, the authors point out.

Indeed, ICU admissions with sepsis accounted for 47.3% of all hospital days and for 46.1% of the aggregate hospital charges among all MS patients admitted to the ICU.

“The adjusted probability of short-term mortality was 13.4% (95% CI, 13.0-13.7) among ICU admissions with sepsis and 3.3% (95% CI, 3.2-3.4) among ICU admissions without sepsis,” the authors report.

This translated into a 44% higher risk of short-term mortality at an adjusted odds ratio of 1.44 (95% CI, 1.23-1.69; P < .0001) for those with sepsis, compared with those without, they add. Among all ICU admissions, sepsis was reported in over two-thirds of documented short-term mortality events. The risk of short-term mortality was also almost threefold higher among patients with sepsis who were age 65 years and older compared with patients aged 18-44. 

As Dr. Oud noted, there is no specific test for sepsis, and it can initially present in an atypical manner, especially in older, frailer, chronically ill patients as well as in patients with immune dysfunction. “Thus, considering sepsis as a possible cause of new deterioration in a patient’s condition is essential, along with the timely start of sepsis-related care,” Dr. Oud observed.

A limitation of the study was that the dataset did not include information on the type of MS a patient had, the duration of their illness, the treatment received, the level of disease activity, or the level of disability.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

Sepsis is an alarmingly common cause behind ICU admissions in patients with multiple sclerosis (MS), a retrospective, population-based cohort study indicates.

Furthermore, it contributes to a disproportionately high percentage of the short-term mortality risk among patients with MS admitted to the ICU, findings also show. Short-term mortality risk was defined in the study as a combination of in-hospital death or discharge to hospice.

“We found that the risk of short-term mortality in critically ill patients with MS is four times higher among those with sepsis ... so sepsis appears to be comparatively more lethal among patients with MS than in the general population,” Lavi Oud, MD, professor of medicine, Texas Tech University HSC at the Permian Basin, Odessa, said in an email.

“[Although] the specific mechanisms underlying the markedly higher risk of sepsis among patients with MS compared to the general population remain to be fully elucidated ... it’s thought that the risk may stem from the dysfunction of the immune system in these patients related to MS itself and to the potentially adverse effect of the immunomodulating therapy we use in these patients,” he added.

The study was published online Jan. 11 in the Journal of Critical Care.
 

Sepsis rates

The Texas Inpatient Public Use Data File was used to identify adults with a diagnosis of MS admitted to the hospital between 2010 and 2017. Among the 19,837 patients with MS admitted to the ICU during the study interval, almost one-third (31.5%) had sepsis, investigators report. “The rate of sepsis among ICU admissions increased with age, ranging from 20.8% among those aged 18-44 to 39.4% among those aged 65 years or older,” investigators note.

The most common site of infection among MS patients admitted to the ICU were urinary in nature (65.2%), followed by respiratory (36.1%). A smaller proportion of infections (7.6%) involved the skin and soft tissues, researchers note. A full one-quarter of patients developed septic shock in response to their infection while the length of stay among patients with sepsis (mean of 10.9 days) was substantially longer than it was for those without sepsis (mean of 5.6 days), they observe.

At a mean total hospital cost of $121,797 for each ICU patient with sepsis, the cost of caring for each patient was nearly twofold higher than the mean total cost of taking care of ICU patients without sepsis (mean total cost, $65,179). On adjusted analysis, sepsis was associated with a 42.7% (95% confidence interval, 38.9-46.5; P < .0001) longer length of hospital stay and a 26.2% (95% CI, 23.1-29.1; P < .0001) higher total hospital cost compared with patients without sepsis, the authors point out.

Indeed, ICU admissions with sepsis accounted for 47.3% of all hospital days and for 46.1% of the aggregate hospital charges among all MS patients admitted to the ICU.

“The adjusted probability of short-term mortality was 13.4% (95% CI, 13.0-13.7) among ICU admissions with sepsis and 3.3% (95% CI, 3.2-3.4) among ICU admissions without sepsis,” the authors report.

This translated into a 44% higher risk of short-term mortality at an adjusted odds ratio of 1.44 (95% CI, 1.23-1.69; P < .0001) for those with sepsis, compared with those without, they add. Among all ICU admissions, sepsis was reported in over two-thirds of documented short-term mortality events. The risk of short-term mortality was also almost threefold higher among patients with sepsis who were age 65 years and older compared with patients aged 18-44. 

As Dr. Oud noted, there is no specific test for sepsis, and it can initially present in an atypical manner, especially in older, frailer, chronically ill patients as well as in patients with immune dysfunction. “Thus, considering sepsis as a possible cause of new deterioration in a patient’s condition is essential, along with the timely start of sepsis-related care,” Dr. Oud observed.

A limitation of the study was that the dataset did not include information on the type of MS a patient had, the duration of their illness, the treatment received, the level of disease activity, or the level of disability.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

Sepsis is an alarmingly common cause behind ICU admissions in patients with multiple sclerosis (MS), a retrospective, population-based cohort study indicates.

Furthermore, it contributes to a disproportionately high percentage of the short-term mortality risk among patients with MS admitted to the ICU, findings also show. Short-term mortality risk was defined in the study as a combination of in-hospital death or discharge to hospice.

“We found that the risk of short-term mortality in critically ill patients with MS is four times higher among those with sepsis ... so sepsis appears to be comparatively more lethal among patients with MS than in the general population,” Lavi Oud, MD, professor of medicine, Texas Tech University HSC at the Permian Basin, Odessa, said in an email.

“[Although] the specific mechanisms underlying the markedly higher risk of sepsis among patients with MS compared to the general population remain to be fully elucidated ... it’s thought that the risk may stem from the dysfunction of the immune system in these patients related to MS itself and to the potentially adverse effect of the immunomodulating therapy we use in these patients,” he added.

The study was published online Jan. 11 in the Journal of Critical Care.
 

Sepsis rates

The Texas Inpatient Public Use Data File was used to identify adults with a diagnosis of MS admitted to the hospital between 2010 and 2017. Among the 19,837 patients with MS admitted to the ICU during the study interval, almost one-third (31.5%) had sepsis, investigators report. “The rate of sepsis among ICU admissions increased with age, ranging from 20.8% among those aged 18-44 to 39.4% among those aged 65 years or older,” investigators note.

The most common site of infection among MS patients admitted to the ICU were urinary in nature (65.2%), followed by respiratory (36.1%). A smaller proportion of infections (7.6%) involved the skin and soft tissues, researchers note. A full one-quarter of patients developed septic shock in response to their infection while the length of stay among patients with sepsis (mean of 10.9 days) was substantially longer than it was for those without sepsis (mean of 5.6 days), they observe.

At a mean total hospital cost of $121,797 for each ICU patient with sepsis, the cost of caring for each patient was nearly twofold higher than the mean total cost of taking care of ICU patients without sepsis (mean total cost, $65,179). On adjusted analysis, sepsis was associated with a 42.7% (95% confidence interval, 38.9-46.5; P < .0001) longer length of hospital stay and a 26.2% (95% CI, 23.1-29.1; P < .0001) higher total hospital cost compared with patients without sepsis, the authors point out.

Indeed, ICU admissions with sepsis accounted for 47.3% of all hospital days and for 46.1% of the aggregate hospital charges among all MS patients admitted to the ICU.

“The adjusted probability of short-term mortality was 13.4% (95% CI, 13.0-13.7) among ICU admissions with sepsis and 3.3% (95% CI, 3.2-3.4) among ICU admissions without sepsis,” the authors report.

This translated into a 44% higher risk of short-term mortality at an adjusted odds ratio of 1.44 (95% CI, 1.23-1.69; P < .0001) for those with sepsis, compared with those without, they add. Among all ICU admissions, sepsis was reported in over two-thirds of documented short-term mortality events. The risk of short-term mortality was also almost threefold higher among patients with sepsis who were age 65 years and older compared with patients aged 18-44. 

As Dr. Oud noted, there is no specific test for sepsis, and it can initially present in an atypical manner, especially in older, frailer, chronically ill patients as well as in patients with immune dysfunction. “Thus, considering sepsis as a possible cause of new deterioration in a patient’s condition is essential, along with the timely start of sepsis-related care,” Dr. Oud observed.

A limitation of the study was that the dataset did not include information on the type of MS a patient had, the duration of their illness, the treatment received, the level of disease activity, or the level of disability.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

Use of e-cigarettes was not more effective than other methods at helping cigarette smokers quit, authors of new research found.

From 2013 to 2017, e-cigarette sales in the United States nearly doubled, driven by a rapid uptake of use by adolescents, wrote Riufeng Chen, MD, of the University of California, San Diego, and colleagues, in their paper published in Tobacco Control. However, the subsequent effect of increased e-cigarette use on smoking cessation have not been examined, they said.

In their study, Dr. Chen and colleagues analyzed data from 3,578 previous-year smokers with a recent quit attempt and 1,323 recent former smokers who were part of the PATH cohort in 2017. The participants reported using e-cigarettes or other products to quit cigarette smoking. The primary outcomes were at least 12 months of cigarette abstinence, and tobacco abstinence in 2019. In 2017, 32.8% of established smokers reported trying to quit. Of these, 12.6% used e-cigarettes to help them quit. Cigarette abstinence for at least 12 months for these individuals was 9.9%, which was lower than for those who used either nicotine replacement therapy or a pharmaceutical aid only (15.2%), and about half of the 18.6% abstinence in those who used no products to help them quit.

“In our study, e-cigarettes resulted in seven fewer successful quitters than those who used pharmaceutical aids,” emphasized corresponding author, John P. Pierce, PhD, of the University of California, San Diego.

Among smokers attempting to quit, the adjusted risk difference for cigarette abstinence for a least 12 months with e-cigarettes vs. pharmaceutical aids was –7.3%, and –7.7% for e-cigarettes vs. other smoking cessation methods.

*“Among recent former smokers who had switched to daily use of e-cigarettes in 2017, 43.2% had successfully quit cigarette smoking by 2019, which was similar to those who used e-cigarettes on a nondaily basis (34.6%) or to those who switched to another tobacco product, whether daily (43.6%) or nondaily (44.7%),” the researchers wrote.

The rapid growth in e-cigarette use between 2014 and 2017 has been attributed in part to aggressive marketing of high-nicotine e-cigarettes, they said. “The high-nicotine JUUL e-cigarette has been noted as the closest match to cigarettes in both nicotine delivery and user satisfaction, which should make it one of the best candidates as a product to which smokers could switch in order to maintain their nicotine habit,” they said in their discussion of the findings.

More research needed

The researchers acknowledged the need to review more recent data.

“When we looked ahead to 2019, recent former smokers had started using high-nicotine e-cigarettes. The effectiveness of high-nicotine e-cigarettes at preventing relapse will require another follow-up PATH survey,” they said.

Among recent former smokers, 2.2% reported switching to a high-nicotine e-cigarette. Although individuals who switched to e-cigarettes showed a higher rate of relapse to cigarettes than those who did not switch to other tobacco or e-cigarette products, this difference was not significant.

The study findings were limited by several factors including the observational design and inability to control for all potential confounding factors, the researchers noted. However, the results were strengthened by the use of a large and representative study population, and the inclusion of biological samples to validate self-reported smoking, they said.
 

Several findings surprised study author

Dr. Pierce said he was surprised by several aspects of the study findings.

“First of all, contrary to what we expected, there was a 25% decline in using e-cigarettes to quit, compared to the previous year (not the 40% increase that was expected from the increase in e-cigarette sales) and almost no smokers were using high-nicotine JUUL products to help them quit,” he said. “In this study, e-cigarettes were much less helpful (7 less successful quitters per 100) than pharmaceutical cessation aids in helping people quit,” he added.

“The fact that the proportion of smokers using e-cigarettes for cessation dropped from 17% to 12% was unexpected, and it suggests that the belief that they are a cessation aid is declining,” he said.

The implication for clinical practice is that e-cigarettes are not a useful tool for smoking cessation, Dr. Pierce said. “We are not finding any evidence in this very large nationally representative study that smokers who switch to getting their nicotine from e-cigarettes are less likely to relapse back to cigarette smoking,” he said.

“We don’t know about the high-nicotine versions,” he added. 
 

New review advises against e-cigarettes for cessation

A recent review article published in JAMA supported the use of pharmacotherapy and behavioral support for smokers wanting to quit. In the review, Nancy A. Rigotti, MD, of Massachusetts General Hospital, Boston, and colleagues summarized the evidence for managing tobacco smoking in clinical practice.

“The health risk from cigarette smoking is primarily due to chemicals produced by the burning of tobacco and not to nicotine,” they noted. However, the physical dependence on nicotine makes quitting a challenge, but it is one worth pursuing, the authors said.

The authors of this review identified 30 reviews, 12 randomized clinical trials, and 7 recent guidelines and evidence reviews. Their key message: Pharmacotherapy and behavioral support are effective when used alone, but even more effective when combined. Pharmacotherapy helps reduce the symptoms of nicotine withdrawal, while behavioral intervention tackles the challenge of changing learned behaviors associated with smoking, the researchers said.

Although combining medications, such as varenicline and nicotine replacement therapy or bupropion might improve successful quit rates, these combinations have not been well studied, they noted.

With regard to e-cigarettes, the researchers cited a 2021 Cochrane review of 16,759 individuals who used e-cigarettes for smoking cessation, which found no evidence of harm, but insufficient evidence to asses the balance of risks vs. benefits.

In addition to the lack of randomized trials, “the FDA regulates e-cigarettes as tobacco products, not as medical products and has not evaluated any e-cigarette for medical use as a cessation aid,” the authors of the new review noted.

The review was limited by several factors, including the lack of quality assessment for the selected studies and the exclusion of pharmacotherapy not licensed in the United States.

Commenting on the JAMA paper, Dr. Pierce said, “This review looks like a number of Cochrane Reports that have been published recently. Of course, it only considers randomized trials and not population evidence.”

“If public health had limited itself to this form of evidence, then we still would not know that smoking caused cancer,” he noted. “Randomized trials are very important for testing new drugs; they use selected populations and provide considerable support that is not available in the real world. Sometimes they do not generalize to the population.”
 

Findings may guide patient conversations

The Tobacco Control study was important, because few studies on e-cigarettes have been conducted, said Linda Girgis, MD, a family physician in private practice in South River, N.J., in an interview.

“As clinicians, we do not have a lot of data available in order to make clinical decisions that are evidence based. Also, getting patients to quit smoking is often very difficult, and having more tools available is a great benefit; however, we need to have the evidence that these tools are effective,” she said.

Dr. Girgis also said she was not surprised by the findings.

“Patients still have the same concerns from e-cigarettes regarding nicotine exposure, but just to a lesser degree; and we still don’t know the long-term effects of e-cigarette use, she said. Based on these studies, recommending e-cigarettes for smokers looking to quit may not be the best method, she noted.

“While it may seem reasonable that exposing lungs to lower doses of nicotine will reduce harm, we need to see actual evidence of this. Also, we also need to study the additives that are frequently used in e-cigs, such as artificial flavorings, to see what harms they may pose, she emphasized.

With regard to the JAMA review, Dr. Girgis said she agreed with the recommendations for pharmacotherapy and behavior therapy as first-line treatments for smoking cessation. “There is evidence regarding the efficacy and safety of these methods, and they have been used for decades,” she said.

Dr. Girgis added that there is a role for e-cigarettes in smoking cessation strategies as a method of harm reduction, but pointed out the problem of many people thinking these products are safe and not understanding the hazards they pose.

“They think they can replace smoking with e-cigarettes and be safe from the health risks associated with smoking. I think if the plan were to switch to e-cigarettes for a short period and then quit, there would be a role,” Dr. Girgis said. “However, replacing one risk for another may reduce harm, but doesn’t eliminate it.”

“To continue to use e-cigarettes indefinitely should not be the goal,” she added.

The Tobacco Control study was funded by the National Institutes of Health and the Tobacco-Related Disease Research Program of the University of California. The researchers had no financial conflicts to disclose.

The JAMA study was funded in part by a grant from the National Institute for Health Research, via Cochrane Infrastructure funds to the Cochrane Tobacco Addiction Group. Lead author Dr. Rigotti disclosed funding from the National Heart, Lung, and Blood Institute and Achieve Life Sciences and personal fees from UpToDate and Achieve Life Sciences. Dr. Girgis had no financial conflicts to disclose.

*This article was updated on 2/28/2022.

Use of e-cigarettes was not more effective than other methods at helping cigarette smokers quit, authors of new research found.

From 2013 to 2017, e-cigarette sales in the United States nearly doubled, driven by a rapid uptake of use by adolescents, wrote Riufeng Chen, MD, of the University of California, San Diego, and colleagues, in their paper published in Tobacco Control. However, the subsequent effect of increased e-cigarette use on smoking cessation have not been examined, they said.

In their study, Dr. Chen and colleagues analyzed data from 3,578 previous-year smokers with a recent quit attempt and 1,323 recent former smokers who were part of the PATH cohort in 2017. The participants reported using e-cigarettes or other products to quit cigarette smoking. The primary outcomes were at least 12 months of cigarette abstinence, and tobacco abstinence in 2019. In 2017, 32.8% of established smokers reported trying to quit. Of these, 12.6% used e-cigarettes to help them quit. Cigarette abstinence for at least 12 months for these individuals was 9.9%, which was lower than for those who used either nicotine replacement therapy or a pharmaceutical aid only (15.2%), and about half of the 18.6% abstinence in those who used no products to help them quit.

“In our study, e-cigarettes resulted in seven fewer successful quitters than those who used pharmaceutical aids,” emphasized corresponding author, John P. Pierce, PhD, of the University of California, San Diego.

Among smokers attempting to quit, the adjusted risk difference for cigarette abstinence for a least 12 months with e-cigarettes vs. pharmaceutical aids was –7.3%, and –7.7% for e-cigarettes vs. other smoking cessation methods.

*“Among recent former smokers who had switched to daily use of e-cigarettes in 2017, 43.2% had successfully quit cigarette smoking by 2019, which was similar to those who used e-cigarettes on a nondaily basis (34.6%) or to those who switched to another tobacco product, whether daily (43.6%) or nondaily (44.7%),” the researchers wrote.

The rapid growth in e-cigarette use between 2014 and 2017 has been attributed in part to aggressive marketing of high-nicotine e-cigarettes, they said. “The high-nicotine JUUL e-cigarette has been noted as the closest match to cigarettes in both nicotine delivery and user satisfaction, which should make it one of the best candidates as a product to which smokers could switch in order to maintain their nicotine habit,” they said in their discussion of the findings.

More research needed

The researchers acknowledged the need to review more recent data.

“When we looked ahead to 2019, recent former smokers had started using high-nicotine e-cigarettes. The effectiveness of high-nicotine e-cigarettes at preventing relapse will require another follow-up PATH survey,” they said.

Among recent former smokers, 2.2% reported switching to a high-nicotine e-cigarette. Although individuals who switched to e-cigarettes showed a higher rate of relapse to cigarettes than those who did not switch to other tobacco or e-cigarette products, this difference was not significant.

The study findings were limited by several factors including the observational design and inability to control for all potential confounding factors, the researchers noted. However, the results were strengthened by the use of a large and representative study population, and the inclusion of biological samples to validate self-reported smoking, they said.
 

Several findings surprised study author

Dr. Pierce said he was surprised by several aspects of the study findings.

“First of all, contrary to what we expected, there was a 25% decline in using e-cigarettes to quit, compared to the previous year (not the 40% increase that was expected from the increase in e-cigarette sales) and almost no smokers were using high-nicotine JUUL products to help them quit,” he said. “In this study, e-cigarettes were much less helpful (7 less successful quitters per 100) than pharmaceutical cessation aids in helping people quit,” he added.

“The fact that the proportion of smokers using e-cigarettes for cessation dropped from 17% to 12% was unexpected, and it suggests that the belief that they are a cessation aid is declining,” he said.

The implication for clinical practice is that e-cigarettes are not a useful tool for smoking cessation, Dr. Pierce said. “We are not finding any evidence in this very large nationally representative study that smokers who switch to getting their nicotine from e-cigarettes are less likely to relapse back to cigarette smoking,” he said.

“We don’t know about the high-nicotine versions,” he added. 
 

New review advises against e-cigarettes for cessation

A recent review article published in JAMA supported the use of pharmacotherapy and behavioral support for smokers wanting to quit. In the review, Nancy A. Rigotti, MD, of Massachusetts General Hospital, Boston, and colleagues summarized the evidence for managing tobacco smoking in clinical practice.

“The health risk from cigarette smoking is primarily due to chemicals produced by the burning of tobacco and not to nicotine,” they noted. However, the physical dependence on nicotine makes quitting a challenge, but it is one worth pursuing, the authors said.

The authors of this review identified 30 reviews, 12 randomized clinical trials, and 7 recent guidelines and evidence reviews. Their key message: Pharmacotherapy and behavioral support are effective when used alone, but even more effective when combined. Pharmacotherapy helps reduce the symptoms of nicotine withdrawal, while behavioral intervention tackles the challenge of changing learned behaviors associated with smoking, the researchers said.

Although combining medications, such as varenicline and nicotine replacement therapy or bupropion might improve successful quit rates, these combinations have not been well studied, they noted.

With regard to e-cigarettes, the researchers cited a 2021 Cochrane review of 16,759 individuals who used e-cigarettes for smoking cessation, which found no evidence of harm, but insufficient evidence to asses the balance of risks vs. benefits.

In addition to the lack of randomized trials, “the FDA regulates e-cigarettes as tobacco products, not as medical products and has not evaluated any e-cigarette for medical use as a cessation aid,” the authors of the new review noted.

The review was limited by several factors, including the lack of quality assessment for the selected studies and the exclusion of pharmacotherapy not licensed in the United States.

Commenting on the JAMA paper, Dr. Pierce said, “This review looks like a number of Cochrane Reports that have been published recently. Of course, it only considers randomized trials and not population evidence.”

“If public health had limited itself to this form of evidence, then we still would not know that smoking caused cancer,” he noted. “Randomized trials are very important for testing new drugs; they use selected populations and provide considerable support that is not available in the real world. Sometimes they do not generalize to the population.”
 

Findings may guide patient conversations

The Tobacco Control study was important, because few studies on e-cigarettes have been conducted, said Linda Girgis, MD, a family physician in private practice in South River, N.J., in an interview.

“As clinicians, we do not have a lot of data available in order to make clinical decisions that are evidence based. Also, getting patients to quit smoking is often very difficult, and having more tools available is a great benefit; however, we need to have the evidence that these tools are effective,” she said.

Dr. Girgis also said she was not surprised by the findings.

“Patients still have the same concerns from e-cigarettes regarding nicotine exposure, but just to a lesser degree; and we still don’t know the long-term effects of e-cigarette use, she said. Based on these studies, recommending e-cigarettes for smokers looking to quit may not be the best method, she noted.

“While it may seem reasonable that exposing lungs to lower doses of nicotine will reduce harm, we need to see actual evidence of this. Also, we also need to study the additives that are frequently used in e-cigs, such as artificial flavorings, to see what harms they may pose, she emphasized.

With regard to the JAMA review, Dr. Girgis said she agreed with the recommendations for pharmacotherapy and behavior therapy as first-line treatments for smoking cessation. “There is evidence regarding the efficacy and safety of these methods, and they have been used for decades,” she said.

Dr. Girgis added that there is a role for e-cigarettes in smoking cessation strategies as a method of harm reduction, but pointed out the problem of many people thinking these products are safe and not understanding the hazards they pose.

“They think they can replace smoking with e-cigarettes and be safe from the health risks associated with smoking. I think if the plan were to switch to e-cigarettes for a short period and then quit, there would be a role,” Dr. Girgis said. “However, replacing one risk for another may reduce harm, but doesn’t eliminate it.”

“To continue to use e-cigarettes indefinitely should not be the goal,” she added.

The Tobacco Control study was funded by the National Institutes of Health and the Tobacco-Related Disease Research Program of the University of California. The researchers had no financial conflicts to disclose.

The JAMA study was funded in part by a grant from the National Institute for Health Research, via Cochrane Infrastructure funds to the Cochrane Tobacco Addiction Group. Lead author Dr. Rigotti disclosed funding from the National Heart, Lung, and Blood Institute and Achieve Life Sciences and personal fees from UpToDate and Achieve Life Sciences. Dr. Girgis had no financial conflicts to disclose.

*This article was updated on 2/28/2022.

Use of e-cigarettes was not more effective than other methods at helping cigarette smokers quit, authors of new research found.

From 2013 to 2017, e-cigarette sales in the United States nearly doubled, driven by a rapid uptake of use by adolescents, wrote Riufeng Chen, MD, of the University of California, San Diego, and colleagues, in their paper published in Tobacco Control. However, the subsequent effect of increased e-cigarette use on smoking cessation have not been examined, they said.

In their study, Dr. Chen and colleagues analyzed data from 3,578 previous-year smokers with a recent quit attempt and 1,323 recent former smokers who were part of the PATH cohort in 2017. The participants reported using e-cigarettes or other products to quit cigarette smoking. The primary outcomes were at least 12 months of cigarette abstinence, and tobacco abstinence in 2019. In 2017, 32.8% of established smokers reported trying to quit. Of these, 12.6% used e-cigarettes to help them quit. Cigarette abstinence for at least 12 months for these individuals was 9.9%, which was lower than for those who used either nicotine replacement therapy or a pharmaceutical aid only (15.2%), and about half of the 18.6% abstinence in those who used no products to help them quit.

“In our study, e-cigarettes resulted in seven fewer successful quitters than those who used pharmaceutical aids,” emphasized corresponding author, John P. Pierce, PhD, of the University of California, San Diego.

Among smokers attempting to quit, the adjusted risk difference for cigarette abstinence for a least 12 months with e-cigarettes vs. pharmaceutical aids was –7.3%, and –7.7% for e-cigarettes vs. other smoking cessation methods.

*“Among recent former smokers who had switched to daily use of e-cigarettes in 2017, 43.2% had successfully quit cigarette smoking by 2019, which was similar to those who used e-cigarettes on a nondaily basis (34.6%) or to those who switched to another tobacco product, whether daily (43.6%) or nondaily (44.7%),” the researchers wrote.

The rapid growth in e-cigarette use between 2014 and 2017 has been attributed in part to aggressive marketing of high-nicotine e-cigarettes, they said. “The high-nicotine JUUL e-cigarette has been noted as the closest match to cigarettes in both nicotine delivery and user satisfaction, which should make it one of the best candidates as a product to which smokers could switch in order to maintain their nicotine habit,” they said in their discussion of the findings.

More research needed

The researchers acknowledged the need to review more recent data.

“When we looked ahead to 2019, recent former smokers had started using high-nicotine e-cigarettes. The effectiveness of high-nicotine e-cigarettes at preventing relapse will require another follow-up PATH survey,” they said.

Among recent former smokers, 2.2% reported switching to a high-nicotine e-cigarette. Although individuals who switched to e-cigarettes showed a higher rate of relapse to cigarettes than those who did not switch to other tobacco or e-cigarette products, this difference was not significant.

The study findings were limited by several factors including the observational design and inability to control for all potential confounding factors, the researchers noted. However, the results were strengthened by the use of a large and representative study population, and the inclusion of biological samples to validate self-reported smoking, they said.
 

Several findings surprised study author

Dr. Pierce said he was surprised by several aspects of the study findings.

“First of all, contrary to what we expected, there was a 25% decline in using e-cigarettes to quit, compared to the previous year (not the 40% increase that was expected from the increase in e-cigarette sales) and almost no smokers were using high-nicotine JUUL products to help them quit,” he said. “In this study, e-cigarettes were much less helpful (7 less successful quitters per 100) than pharmaceutical cessation aids in helping people quit,” he added.

“The fact that the proportion of smokers using e-cigarettes for cessation dropped from 17% to 12% was unexpected, and it suggests that the belief that they are a cessation aid is declining,” he said.

The implication for clinical practice is that e-cigarettes are not a useful tool for smoking cessation, Dr. Pierce said. “We are not finding any evidence in this very large nationally representative study that smokers who switch to getting their nicotine from e-cigarettes are less likely to relapse back to cigarette smoking,” he said.

“We don’t know about the high-nicotine versions,” he added. 
 

New review advises against e-cigarettes for cessation

A recent review article published in JAMA supported the use of pharmacotherapy and behavioral support for smokers wanting to quit. In the review, Nancy A. Rigotti, MD, of Massachusetts General Hospital, Boston, and colleagues summarized the evidence for managing tobacco smoking in clinical practice.

“The health risk from cigarette smoking is primarily due to chemicals produced by the burning of tobacco and not to nicotine,” they noted. However, the physical dependence on nicotine makes quitting a challenge, but it is one worth pursuing, the authors said.

The authors of this review identified 30 reviews, 12 randomized clinical trials, and 7 recent guidelines and evidence reviews. Their key message: Pharmacotherapy and behavioral support are effective when used alone, but even more effective when combined. Pharmacotherapy helps reduce the symptoms of nicotine withdrawal, while behavioral intervention tackles the challenge of changing learned behaviors associated with smoking, the researchers said.

Although combining medications, such as varenicline and nicotine replacement therapy or bupropion might improve successful quit rates, these combinations have not been well studied, they noted.

With regard to e-cigarettes, the researchers cited a 2021 Cochrane review of 16,759 individuals who used e-cigarettes for smoking cessation, which found no evidence of harm, but insufficient evidence to asses the balance of risks vs. benefits.

In addition to the lack of randomized trials, “the FDA regulates e-cigarettes as tobacco products, not as medical products and has not evaluated any e-cigarette for medical use as a cessation aid,” the authors of the new review noted.

The review was limited by several factors, including the lack of quality assessment for the selected studies and the exclusion of pharmacotherapy not licensed in the United States.

Commenting on the JAMA paper, Dr. Pierce said, “This review looks like a number of Cochrane Reports that have been published recently. Of course, it only considers randomized trials and not population evidence.”

“If public health had limited itself to this form of evidence, then we still would not know that smoking caused cancer,” he noted. “Randomized trials are very important for testing new drugs; they use selected populations and provide considerable support that is not available in the real world. Sometimes they do not generalize to the population.”
 

Findings may guide patient conversations

The Tobacco Control study was important, because few studies on e-cigarettes have been conducted, said Linda Girgis, MD, a family physician in private practice in South River, N.J., in an interview.

“As clinicians, we do not have a lot of data available in order to make clinical decisions that are evidence based. Also, getting patients to quit smoking is often very difficult, and having more tools available is a great benefit; however, we need to have the evidence that these tools are effective,” she said.

Dr. Girgis also said she was not surprised by the findings.

“Patients still have the same concerns from e-cigarettes regarding nicotine exposure, but just to a lesser degree; and we still don’t know the long-term effects of e-cigarette use, she said. Based on these studies, recommending e-cigarettes for smokers looking to quit may not be the best method, she noted.

“While it may seem reasonable that exposing lungs to lower doses of nicotine will reduce harm, we need to see actual evidence of this. Also, we also need to study the additives that are frequently used in e-cigs, such as artificial flavorings, to see what harms they may pose, she emphasized.

With regard to the JAMA review, Dr. Girgis said she agreed with the recommendations for pharmacotherapy and behavior therapy as first-line treatments for smoking cessation. “There is evidence regarding the efficacy and safety of these methods, and they have been used for decades,” she said.

Dr. Girgis added that there is a role for e-cigarettes in smoking cessation strategies as a method of harm reduction, but pointed out the problem of many people thinking these products are safe and not understanding the hazards they pose.

“They think they can replace smoking with e-cigarettes and be safe from the health risks associated with smoking. I think if the plan were to switch to e-cigarettes for a short period and then quit, there would be a role,” Dr. Girgis said. “However, replacing one risk for another may reduce harm, but doesn’t eliminate it.”

“To continue to use e-cigarettes indefinitely should not be the goal,” she added.

The Tobacco Control study was funded by the National Institutes of Health and the Tobacco-Related Disease Research Program of the University of California. The researchers had no financial conflicts to disclose.

The JAMA study was funded in part by a grant from the National Institute for Health Research, via Cochrane Infrastructure funds to the Cochrane Tobacco Addiction Group. Lead author Dr. Rigotti disclosed funding from the National Heart, Lung, and Blood Institute and Achieve Life Sciences and personal fees from UpToDate and Achieve Life Sciences. Dr. Girgis had no financial conflicts to disclose.

*This article was updated on 2/28/2022.