Heidi Splete

Almost all patients with both obstructive sleep apnea syndrome and severe asthma fell into the obesity phenotype, not the allergy phenotype, based on data from nearly 1,500 adults.

Both asthma and sleep-disordered breathing are common conditions worldwide, and previous research suggests that obstructive sleep apnea syndrome (OSAS) and severe asthma in particular could be associated, wrote Laurent Portel, MD, of Centre Hospitalier de Libourne, France, and colleagues.

“Even if the underlying mechanisms are not well established, it is clear that both OSAS and obesity act to aggravate existing asthma, making it more difficult to control,” they said. However, the pathology of this relationship is not well-understood, and data on severe asthma phenotypes and OSAS are limited, they said.

In a study published in Respiratory Medicine and Research, the investigators reviewed data from 1,465 patients older than 18 years with severe asthma who were part of a larger, prospective multicenter study of the management of asthma patients. The larger study, developed by the Collège des Pneumologues des Hôpitaux Généraux (CPHG) is known as the FASE-CPHG (France Asthme SEvère-CPHG) and includes 104 nonacademic hospitals in France.

Diagnosis of OSAS was reported by physicians; diagnosis of severe asthma was based on the Global Initiative for Asthma criteria. The average age of the patients was 54.4 years, 63% were women, and 60% were nonsmokers.

A total of 161 patients were diagnosed with OSAS. The researchers conducted a cluster analysis on 1,424 patients, including 156 of the OSAS patients. They identified five clusters: early-onset atopic asthma (690 patients), obese asthma (153 patients), late-onset asthma (299 patients), eosinophilic asthma (143 patients), and aspirin sensitivity asthma (139 patients).

All 153 patients in the obese asthma cluster had OSAS, by contrast, none of the patients in the early atopic asthma cluster had OSAS.

Overall, obesity, male sex, high blood pressure, depression, late-onset asthma, and early-onset atopic asthma were independently associated with OSAS, with odds ratios of 5.782, 3.047, 2.875, 2.552, 1.789, and 0.622, respectively.

Notably, OSAS patients were more frequently treated with long-term oral corticosteroids than those without OSAS (30% vs. 15%, P < .0001), the researchers said. “It is possible that this treatment may be responsible for obesity, and it represents a well-known risk factor for developing OSAS,” they wrote.

Uncontrolled asthma was significantly more common in OSAS patients than in those without OSAS (77.7% vs. 69%, P = .03), and significantly more OSAS patients reported no or occasional physical activity (79.8% vs. 68.2%, P ≤ .001).

The study findings were limited by several factors including the lack of patients from primary care or university hospitals, which may limit the generalizability of the results, the reliance on physician statements for diagnosis of OSAS, and the lack of data on OSAS severity or treatment, the researchers noted.

However, the results fill a needed gap in the literature because of the limited data on severe asthma patients in real life, and identifying severe asthma patients by phenotype may help identify those at greatest risk for OSAS, they said.

“Identified patients could more easily benefit from specific examinations such as poly(somno)graphy and, consequently, could benefit from a better management of both asthma and OSAS,” they emphasized.

The larger FASE-CPHG study was supported in part by ALK, AstraZeneca, Boehringer Ingelheim, GSK, and Le Nouveau Souffle. The researchers had no financial conflicts to disclose.

Almost all patients with both obstructive sleep apnea syndrome and severe asthma fell into the obesity phenotype, not the allergy phenotype, based on data from nearly 1,500 adults.

Both asthma and sleep-disordered breathing are common conditions worldwide, and previous research suggests that obstructive sleep apnea syndrome (OSAS) and severe asthma in particular could be associated, wrote Laurent Portel, MD, of Centre Hospitalier de Libourne, France, and colleagues.

“Even if the underlying mechanisms are not well established, it is clear that both OSAS and obesity act to aggravate existing asthma, making it more difficult to control,” they said. However, the pathology of this relationship is not well-understood, and data on severe asthma phenotypes and OSAS are limited, they said.

In a study published in Respiratory Medicine and Research, the investigators reviewed data from 1,465 patients older than 18 years with severe asthma who were part of a larger, prospective multicenter study of the management of asthma patients. The larger study, developed by the Collège des Pneumologues des Hôpitaux Généraux (CPHG) is known as the FASE-CPHG (France Asthme SEvère-CPHG) and includes 104 nonacademic hospitals in France.

Diagnosis of OSAS was reported by physicians; diagnosis of severe asthma was based on the Global Initiative for Asthma criteria. The average age of the patients was 54.4 years, 63% were women, and 60% were nonsmokers.

A total of 161 patients were diagnosed with OSAS. The researchers conducted a cluster analysis on 1,424 patients, including 156 of the OSAS patients. They identified five clusters: early-onset atopic asthma (690 patients), obese asthma (153 patients), late-onset asthma (299 patients), eosinophilic asthma (143 patients), and aspirin sensitivity asthma (139 patients).

All 153 patients in the obese asthma cluster had OSAS, by contrast, none of the patients in the early atopic asthma cluster had OSAS.

Overall, obesity, male sex, high blood pressure, depression, late-onset asthma, and early-onset atopic asthma were independently associated with OSAS, with odds ratios of 5.782, 3.047, 2.875, 2.552, 1.789, and 0.622, respectively.

Notably, OSAS patients were more frequently treated with long-term oral corticosteroids than those without OSAS (30% vs. 15%, P < .0001), the researchers said. “It is possible that this treatment may be responsible for obesity, and it represents a well-known risk factor for developing OSAS,” they wrote.

Uncontrolled asthma was significantly more common in OSAS patients than in those without OSAS (77.7% vs. 69%, P = .03), and significantly more OSAS patients reported no or occasional physical activity (79.8% vs. 68.2%, P ≤ .001).

The study findings were limited by several factors including the lack of patients from primary care or university hospitals, which may limit the generalizability of the results, the reliance on physician statements for diagnosis of OSAS, and the lack of data on OSAS severity or treatment, the researchers noted.

However, the results fill a needed gap in the literature because of the limited data on severe asthma patients in real life, and identifying severe asthma patients by phenotype may help identify those at greatest risk for OSAS, they said.

“Identified patients could more easily benefit from specific examinations such as poly(somno)graphy and, consequently, could benefit from a better management of both asthma and OSAS,” they emphasized.

The larger FASE-CPHG study was supported in part by ALK, AstraZeneca, Boehringer Ingelheim, GSK, and Le Nouveau Souffle. The researchers had no financial conflicts to disclose.

Almost all patients with both obstructive sleep apnea syndrome and severe asthma fell into the obesity phenotype, not the allergy phenotype, based on data from nearly 1,500 adults.

Both asthma and sleep-disordered breathing are common conditions worldwide, and previous research suggests that obstructive sleep apnea syndrome (OSAS) and severe asthma in particular could be associated, wrote Laurent Portel, MD, of Centre Hospitalier de Libourne, France, and colleagues.

“Even if the underlying mechanisms are not well established, it is clear that both OSAS and obesity act to aggravate existing asthma, making it more difficult to control,” they said. However, the pathology of this relationship is not well-understood, and data on severe asthma phenotypes and OSAS are limited, they said.

In a study published in Respiratory Medicine and Research, the investigators reviewed data from 1,465 patients older than 18 years with severe asthma who were part of a larger, prospective multicenter study of the management of asthma patients. The larger study, developed by the Collège des Pneumologues des Hôpitaux Généraux (CPHG) is known as the FASE-CPHG (France Asthme SEvère-CPHG) and includes 104 nonacademic hospitals in France.

Diagnosis of OSAS was reported by physicians; diagnosis of severe asthma was based on the Global Initiative for Asthma criteria. The average age of the patients was 54.4 years, 63% were women, and 60% were nonsmokers.

A total of 161 patients were diagnosed with OSAS. The researchers conducted a cluster analysis on 1,424 patients, including 156 of the OSAS patients. They identified five clusters: early-onset atopic asthma (690 patients), obese asthma (153 patients), late-onset asthma (299 patients), eosinophilic asthma (143 patients), and aspirin sensitivity asthma (139 patients).

All 153 patients in the obese asthma cluster had OSAS, by contrast, none of the patients in the early atopic asthma cluster had OSAS.

Overall, obesity, male sex, high blood pressure, depression, late-onset asthma, and early-onset atopic asthma were independently associated with OSAS, with odds ratios of 5.782, 3.047, 2.875, 2.552, 1.789, and 0.622, respectively.

Notably, OSAS patients were more frequently treated with long-term oral corticosteroids than those without OSAS (30% vs. 15%, P < .0001), the researchers said. “It is possible that this treatment may be responsible for obesity, and it represents a well-known risk factor for developing OSAS,” they wrote.

Uncontrolled asthma was significantly more common in OSAS patients than in those without OSAS (77.7% vs. 69%, P = .03), and significantly more OSAS patients reported no or occasional physical activity (79.8% vs. 68.2%, P ≤ .001).

The study findings were limited by several factors including the lack of patients from primary care or university hospitals, which may limit the generalizability of the results, the reliance on physician statements for diagnosis of OSAS, and the lack of data on OSAS severity or treatment, the researchers noted.

However, the results fill a needed gap in the literature because of the limited data on severe asthma patients in real life, and identifying severe asthma patients by phenotype may help identify those at greatest risk for OSAS, they said.

“Identified patients could more easily benefit from specific examinations such as poly(somno)graphy and, consequently, could benefit from a better management of both asthma and OSAS,” they emphasized.

The larger FASE-CPHG study was supported in part by ALK, AstraZeneca, Boehringer Ingelheim, GSK, and Le Nouveau Souffle. The researchers had no financial conflicts to disclose.

New studies show that chronic exposure to air pollution is associated with increased risk of autoimmune disease in adults and depression in adolescents.

Other analyses of data have found environmental air pollution from sources such as car exhaust and factory output can trigger an inflammatory response in the body. What’s new about a study published in RMD Open is that it explored an association between long-term exposure to pollution and risk of autoimmune diseases, wrote Giovanni Adami, MD, of the University of Verona (Italy) and colleagues.

“Environmental air pollution, according to the World Health Organization, is a major risk to health and 99% of the population worldwide is living in places where recommendations for air quality are not met,” said Dr. Adami in an interview. The limited data on the precise role of air pollution on rheumatic diseases in particular prompted the study, he said.

To explore the potential link between air pollution exposure and autoimmune disease, the researchers reviewed medical information from 81,363 adults via a national medical database in Italy; the data were submitted between June 2016 and November 2020.

The average age of the study population was 65 years, and 92% were women; 22% had at least one coexisting health condition. Each study participant was linked to local environmental monitoring via their residential postcode. 

The researchers obtained details about concentrations of particulate matter in the environment from the Italian Institute of Environmental Protection that included 617 monitoring stations in 110 Italian provinces. They focused on concentrations of 10 and 2.5 (PM10 and PM2.5).

Exposure thresholds of 30 mcg/m³ for PM10 and 20 mcg/m³ for PM2.5 are generally considered harmful to health, they noted. On average, the long-term exposure was 16 mcg/m³ for PM2.5 and 25 mcg/m³ for PM10 between 2013 and 2019.

Overall, 9,723 individuals (12%) were diagnosed with an autoimmune disease between 2016 and 2020.

Exposure to PM10 was associated with a 7% higher risk of diagnosis with any autoimmune disease for every 10 mcg/m³ increase in concentration, but no association appeared between PM2.5 exposure and increased risk of autoimmune diseases.

However, in an adjusted model, chronic exposure to PM10 above 30 mcg/m³ and to PM2.5 above 20 mcg/m³ were associated with a 12% and 13% higher risk, respectively, of any autoimmune disease. 

Chronic exposure to high levels of PM10 was specifically associated with a higher risk of rheumatoid arthritis, but no other autoimmune diseases. Chronic exposure to high levels of PM2.5 was associated with a higher risk of rheumatoid arthritis, connective tissue diseases, and inflammatory bowel diseases.

In their discussion, the researchers noted that the smaller diameter of PM2.5 molecules fluctuate less in response to rain and other weather, compared with PM10 molecules, which might make them a more accurate predictor of exposure to chronic air pollution.

The study findings were limited by several factors including the observational design, which prohibits the establishment of cause, and a lack of data on the start of symptoms and dates of diagnoses for autoimmune diseases, the researchers noted. Other limitations include the high percentage of older women in the study, which may limit generalizability, and the inability to account for additional personal exposure to pollutants outside of the environmental exposure, they said.

However, the results were strengthened by the large sample size and wide geographic distribution with variable pollution exposure, they said.

“Unfortunately, we were not surprised at all,” by the findings, Dr. Adami said in an interview.

“The biological rationale underpinning our findings is strong. Nevertheless, the magnitude of the effect was overwhelming. In addition, we saw an effect even at threshold of exposure that is widely considered as safe,” Dr. Adami noted.

Clinicians have been taught to consider cigarette smoking or other lifestyle behaviors as major risk factors for the development of several autoimmune diseases, said Dr. Adami. “In the future, we probably should include air pollution exposure as a risk factor as well. Interestingly, there is also accumulating evidence linking acute exposure to environmental air pollution with flares of chronic arthritis,” he said.

“Our study could have direct societal and political consequences,” and might help direct policy makers’ decisions on addressing strategies aimed to reduce fossil emissions, he said. As for additional research, “we certainly need multination studies to confirm our results on a larger scale,” Dr. Adami emphasized. “In addition, it is time to take action and start designing interventions aimed to reduce acute and chronic exposure to air pollution in patients suffering from RMDs.”

Consider the big picture of air quality

The Italian study is especially timely “given our evolving and emerging understanding of environmental risk factors for acute and chronic diseases, which we must first understand before we can address,” said Eileen Barrett, MD, of the University of New Mexico, Albuquerque, in an interview.

“I am largely surprised about the findings, as most physicians aren’t studying ambient air quality and risk for autoimmune disease,” said Dr. Barrett. “More often we think of air quality when we think of risk for respiratory diseases than autoimmune diseases, per se,” she said.

“There are several take-home messages from this study,” said Dr. Barrett. “The first is that we need more research to understand the consequences of air pollutants on health. Second, this study reminds us to think broadly about how air quality and our environment can affect health. And third, all clinicians should be committed to promoting science that can improve public health and reduce death and disability,” she emphasized.

The findings do not specifically reflect associations between pollution and other conditions such as chronic obstructive pulmonary disease and asthma although previous studies have shown an association between asthma and COPD exacerbations and air pollution, Dr. Barrett said.

“Further research will be needed to confirm the associations reported in this study,” Dr. Barrett said.

More research in other countries, including research related to other autoimmune diseases, and with other datasets on population and community level risks from poor air quality, would be helpful, and that information could be used to advise smart public policy, Dr. Barrett added.

Air pollution’s mental health impact

Air pollution’s effects extend beyond physical to the psychological, a new study of depression in teenagers showed. This study was published in Developmental Psychology.

Previous research on the environmental factors associated with depressive symptoms in teens has focused mainly on individual and family level contributors; the impact of the physical environment has not been well studied, the investigators, Erika M. Manczak, PhD, of the University of Denver and colleagues, wrote.

In their paper, the authors found a significant impact of neighborhood ozone exposure on the trajectory of depressive symptoms in teens over a 4-year period.

“Given that inhaling pollution activates biological pathways implicated in the development of depression, including immune, cardiovascular, and neurodevelopmental processes, exposure to ambient air pollution may influence the development and/or trajectory of depressive symptoms in youth,” they said.

The researchers recruited 213 adolescents in the San Francisco Bay area through local advertisements. The participants were aged 9-13 years at baseline, with an average age of 11 years. A total of 121 were female, 47% were white, 8.5% were African American, 12.3% were Asian, 10.4% were nonwhite Latin, and 21.7% were biracial or another ethnicity. The participants self-reported depressive symptoms and other psychopathology symptoms up to three times during the study period. Ozone exposure was calculated based on home addresses.

After controlling for other personal, family, and neighborhood variables, the researchers found that higher levels of ozone exposure were significantly associated with increased depressive symptoms over time, and the slope of trajectory of depressive symptoms became steeper as the ozone levels increased (P less than .001). Ozone did not significantly predict the trajectory of any other psychopathology symptoms.

“The results of this study provide preliminary support for the possibility that ozone is an overlooked contributor to the development or course of youth depressive symptoms,” the researchers wrote in their discussion.

“Interestingly, the association between ozone and symptom trajectories as measured by Anxious/Depressed subscale of the [Youth Self-Report] was not as strong as it was for the [Children’s Depression Inventory-Short Version] or Withdrawn/Depressed scales, suggesting that associations are more robust for behavioral withdrawal symptoms of depression than for other types of symptoms,” they noted.

The study findings were limited by the use of self-reports and by the inability of the study design to show causality, the researchers said. Other limitations include the use of average assessments of ozone that are less precise, lack of assessment of biological pathways for risk, lack of formal psychiatric diagnoses, and the small geographic region included in the study, they said.

However, the results provide preliminary evidence that ozone exposure is a potential contributing factor to depressive symptoms in youth, and serve as a jumping-off point for future research, they noted. Future studies should address changes in systemic inflammation, neurodevelopment, or stress reactivity, as well as concurrent psychosocial or biological factors, and temporal associations between air pollution and mental health symptoms, they concluded.

Environmental factors drive inflammatory responses

Peter L. Loper Jr., MD, considers the findings of the Developmental Psychology study to be unsurprising but important – because air pollution is simply getting worse.

“As the study authors cite, there is sufficient data correlating ozone to negative physical health outcomes in youth, but a paucity of data exploring the impact of poor air quality on mental health outcomes in this demographic,” noted Dr. Loper, of the University of South Carolina, Columbia, in an interview.

“As discussed by the study researchers, any environmental exposure that increases immune-mediated inflammation can result in negative health outcomes. In fact, there is already data to suggest that similar cytokines, or immune cell signalers, that get released by our immune system due to environmental exposures and that contribute to asthma, may also be implicated in depression and other mental health problems,” he noted.

“Just like downstream symptom indicators of physical illnesses such as asthma are secondary to immune-mediated pulmonary inflammation, downstream symptom indicators of mental illness, such as depression, are secondary to immune-mediated neuroinflammation,” Dr. Loper emphasized. “The most well-characterized upstream phenomenon perpetuating the downstream symptom indicators of depression involve neuroinflammatory states due to psychosocial and relational factors such as chronic stress, poor relationships, or substance use. However, any environmental factor that triggers an immune response and inflammation can promote neuroinflammation that manifests as symptoms of mental illness.”

The message for teens with depression and their families is that “we are a product of our environment,” Dr. Loper said. “When our environments are proinflammatory, or cause our immune system to become overactive, then we will develop illness; however, the most potent mediator of inflammation in the brain, and the downstream symptoms of depression, is our relationships with those we love most,” he said.

Dr. Loper suggested research aimed at identifying other sources of immune-mediated inflammation caused by physical environments and better understanding how environmental phenomenon like ozone may compound previously established risk factors for mental illness could be useful.

The RMD Open study received no outside funding, and its authors had no financial conflicts.

The Developmental Psychology study was supported by the National Institute of Mental Health and the Stanford University Precision Health and Integrated Diagnostics Center. The researchers for that report, and Dr. Loper and Dr. Barrett had no conflicts to disclose.

New studies show that chronic exposure to air pollution is associated with increased risk of autoimmune disease in adults and depression in adolescents.

Other analyses of data have found environmental air pollution from sources such as car exhaust and factory output can trigger an inflammatory response in the body. What’s new about a study published in RMD Open is that it explored an association between long-term exposure to pollution and risk of autoimmune diseases, wrote Giovanni Adami, MD, of the University of Verona (Italy) and colleagues.

“Environmental air pollution, according to the World Health Organization, is a major risk to health and 99% of the population worldwide is living in places where recommendations for air quality are not met,” said Dr. Adami in an interview. The limited data on the precise role of air pollution on rheumatic diseases in particular prompted the study, he said.

To explore the potential link between air pollution exposure and autoimmune disease, the researchers reviewed medical information from 81,363 adults via a national medical database in Italy; the data were submitted between June 2016 and November 2020.

The average age of the study population was 65 years, and 92% were women; 22% had at least one coexisting health condition. Each study participant was linked to local environmental monitoring via their residential postcode. 

The researchers obtained details about concentrations of particulate matter in the environment from the Italian Institute of Environmental Protection that included 617 monitoring stations in 110 Italian provinces. They focused on concentrations of 10 and 2.5 (PM10 and PM2.5).

Exposure thresholds of 30 mcg/m³ for PM10 and 20 mcg/m³ for PM2.5 are generally considered harmful to health, they noted. On average, the long-term exposure was 16 mcg/m³ for PM2.5 and 25 mcg/m³ for PM10 between 2013 and 2019.

Overall, 9,723 individuals (12%) were diagnosed with an autoimmune disease between 2016 and 2020.

Exposure to PM10 was associated with a 7% higher risk of diagnosis with any autoimmune disease for every 10 mcg/m³ increase in concentration, but no association appeared between PM2.5 exposure and increased risk of autoimmune diseases.

However, in an adjusted model, chronic exposure to PM10 above 30 mcg/m³ and to PM2.5 above 20 mcg/m³ were associated with a 12% and 13% higher risk, respectively, of any autoimmune disease. 

Chronic exposure to high levels of PM10 was specifically associated with a higher risk of rheumatoid arthritis, but no other autoimmune diseases. Chronic exposure to high levels of PM2.5 was associated with a higher risk of rheumatoid arthritis, connective tissue diseases, and inflammatory bowel diseases.

In their discussion, the researchers noted that the smaller diameter of PM2.5 molecules fluctuate less in response to rain and other weather, compared with PM10 molecules, which might make them a more accurate predictor of exposure to chronic air pollution.

The study findings were limited by several factors including the observational design, which prohibits the establishment of cause, and a lack of data on the start of symptoms and dates of diagnoses for autoimmune diseases, the researchers noted. Other limitations include the high percentage of older women in the study, which may limit generalizability, and the inability to account for additional personal exposure to pollutants outside of the environmental exposure, they said.

However, the results were strengthened by the large sample size and wide geographic distribution with variable pollution exposure, they said.

“Unfortunately, we were not surprised at all,” by the findings, Dr. Adami said in an interview.

“The biological rationale underpinning our findings is strong. Nevertheless, the magnitude of the effect was overwhelming. In addition, we saw an effect even at threshold of exposure that is widely considered as safe,” Dr. Adami noted.

Clinicians have been taught to consider cigarette smoking or other lifestyle behaviors as major risk factors for the development of several autoimmune diseases, said Dr. Adami. “In the future, we probably should include air pollution exposure as a risk factor as well. Interestingly, there is also accumulating evidence linking acute exposure to environmental air pollution with flares of chronic arthritis,” he said.

“Our study could have direct societal and political consequences,” and might help direct policy makers’ decisions on addressing strategies aimed to reduce fossil emissions, he said. As for additional research, “we certainly need multination studies to confirm our results on a larger scale,” Dr. Adami emphasized. “In addition, it is time to take action and start designing interventions aimed to reduce acute and chronic exposure to air pollution in patients suffering from RMDs.”

Consider the big picture of air quality

The Italian study is especially timely “given our evolving and emerging understanding of environmental risk factors for acute and chronic diseases, which we must first understand before we can address,” said Eileen Barrett, MD, of the University of New Mexico, Albuquerque, in an interview.

“I am largely surprised about the findings, as most physicians aren’t studying ambient air quality and risk for autoimmune disease,” said Dr. Barrett. “More often we think of air quality when we think of risk for respiratory diseases than autoimmune diseases, per se,” she said.

“There are several take-home messages from this study,” said Dr. Barrett. “The first is that we need more research to understand the consequences of air pollutants on health. Second, this study reminds us to think broadly about how air quality and our environment can affect health. And third, all clinicians should be committed to promoting science that can improve public health and reduce death and disability,” she emphasized.

The findings do not specifically reflect associations between pollution and other conditions such as chronic obstructive pulmonary disease and asthma although previous studies have shown an association between asthma and COPD exacerbations and air pollution, Dr. Barrett said.

“Further research will be needed to confirm the associations reported in this study,” Dr. Barrett said.

More research in other countries, including research related to other autoimmune diseases, and with other datasets on population and community level risks from poor air quality, would be helpful, and that information could be used to advise smart public policy, Dr. Barrett added.

Air pollution’s mental health impact

Air pollution’s effects extend beyond physical to the psychological, a new study of depression in teenagers showed. This study was published in Developmental Psychology.

Previous research on the environmental factors associated with depressive symptoms in teens has focused mainly on individual and family level contributors; the impact of the physical environment has not been well studied, the investigators, Erika M. Manczak, PhD, of the University of Denver and colleagues, wrote.

In their paper, the authors found a significant impact of neighborhood ozone exposure on the trajectory of depressive symptoms in teens over a 4-year period.

“Given that inhaling pollution activates biological pathways implicated in the development of depression, including immune, cardiovascular, and neurodevelopmental processes, exposure to ambient air pollution may influence the development and/or trajectory of depressive symptoms in youth,” they said.

The researchers recruited 213 adolescents in the San Francisco Bay area through local advertisements. The participants were aged 9-13 years at baseline, with an average age of 11 years. A total of 121 were female, 47% were white, 8.5% were African American, 12.3% were Asian, 10.4% were nonwhite Latin, and 21.7% were biracial or another ethnicity. The participants self-reported depressive symptoms and other psychopathology symptoms up to three times during the study period. Ozone exposure was calculated based on home addresses.

After controlling for other personal, family, and neighborhood variables, the researchers found that higher levels of ozone exposure were significantly associated with increased depressive symptoms over time, and the slope of trajectory of depressive symptoms became steeper as the ozone levels increased (P less than .001). Ozone did not significantly predict the trajectory of any other psychopathology symptoms.

“The results of this study provide preliminary support for the possibility that ozone is an overlooked contributor to the development or course of youth depressive symptoms,” the researchers wrote in their discussion.

“Interestingly, the association between ozone and symptom trajectories as measured by Anxious/Depressed subscale of the [Youth Self-Report] was not as strong as it was for the [Children’s Depression Inventory-Short Version] or Withdrawn/Depressed scales, suggesting that associations are more robust for behavioral withdrawal symptoms of depression than for other types of symptoms,” they noted.

The study findings were limited by the use of self-reports and by the inability of the study design to show causality, the researchers said. Other limitations include the use of average assessments of ozone that are less precise, lack of assessment of biological pathways for risk, lack of formal psychiatric diagnoses, and the small geographic region included in the study, they said.

However, the results provide preliminary evidence that ozone exposure is a potential contributing factor to depressive symptoms in youth, and serve as a jumping-off point for future research, they noted. Future studies should address changes in systemic inflammation, neurodevelopment, or stress reactivity, as well as concurrent psychosocial or biological factors, and temporal associations between air pollution and mental health symptoms, they concluded.

Environmental factors drive inflammatory responses

Peter L. Loper Jr., MD, considers the findings of the Developmental Psychology study to be unsurprising but important – because air pollution is simply getting worse.

“As the study authors cite, there is sufficient data correlating ozone to negative physical health outcomes in youth, but a paucity of data exploring the impact of poor air quality on mental health outcomes in this demographic,” noted Dr. Loper, of the University of South Carolina, Columbia, in an interview.

“As discussed by the study researchers, any environmental exposure that increases immune-mediated inflammation can result in negative health outcomes. In fact, there is already data to suggest that similar cytokines, or immune cell signalers, that get released by our immune system due to environmental exposures and that contribute to asthma, may also be implicated in depression and other mental health problems,” he noted.

“Just like downstream symptom indicators of physical illnesses such as asthma are secondary to immune-mediated pulmonary inflammation, downstream symptom indicators of mental illness, such as depression, are secondary to immune-mediated neuroinflammation,” Dr. Loper emphasized. “The most well-characterized upstream phenomenon perpetuating the downstream symptom indicators of depression involve neuroinflammatory states due to psychosocial and relational factors such as chronic stress, poor relationships, or substance use. However, any environmental factor that triggers an immune response and inflammation can promote neuroinflammation that manifests as symptoms of mental illness.”

The message for teens with depression and their families is that “we are a product of our environment,” Dr. Loper said. “When our environments are proinflammatory, or cause our immune system to become overactive, then we will develop illness; however, the most potent mediator of inflammation in the brain, and the downstream symptoms of depression, is our relationships with those we love most,” he said.

Dr. Loper suggested research aimed at identifying other sources of immune-mediated inflammation caused by physical environments and better understanding how environmental phenomenon like ozone may compound previously established risk factors for mental illness could be useful.

The RMD Open study received no outside funding, and its authors had no financial conflicts.

The Developmental Psychology study was supported by the National Institute of Mental Health and the Stanford University Precision Health and Integrated Diagnostics Center. The researchers for that report, and Dr. Loper and Dr. Barrett had no conflicts to disclose.

New studies show that chronic exposure to air pollution is associated with increased risk of autoimmune disease in adults and depression in adolescents.

Other analyses of data have found environmental air pollution from sources such as car exhaust and factory output can trigger an inflammatory response in the body. What’s new about a study published in RMD Open is that it explored an association between long-term exposure to pollution and risk of autoimmune diseases, wrote Giovanni Adami, MD, of the University of Verona (Italy) and colleagues.

“Environmental air pollution, according to the World Health Organization, is a major risk to health and 99% of the population worldwide is living in places where recommendations for air quality are not met,” said Dr. Adami in an interview. The limited data on the precise role of air pollution on rheumatic diseases in particular prompted the study, he said.

To explore the potential link between air pollution exposure and autoimmune disease, the researchers reviewed medical information from 81,363 adults via a national medical database in Italy; the data were submitted between June 2016 and November 2020.

The average age of the study population was 65 years, and 92% were women; 22% had at least one coexisting health condition. Each study participant was linked to local environmental monitoring via their residential postcode. 

The researchers obtained details about concentrations of particulate matter in the environment from the Italian Institute of Environmental Protection that included 617 monitoring stations in 110 Italian provinces. They focused on concentrations of 10 and 2.5 (PM10 and PM2.5).

Exposure thresholds of 30 mcg/m³ for PM10 and 20 mcg/m³ for PM2.5 are generally considered harmful to health, they noted. On average, the long-term exposure was 16 mcg/m³ for PM2.5 and 25 mcg/m³ for PM10 between 2013 and 2019.

Overall, 9,723 individuals (12%) were diagnosed with an autoimmune disease between 2016 and 2020.

Exposure to PM10 was associated with a 7% higher risk of diagnosis with any autoimmune disease for every 10 mcg/m³ increase in concentration, but no association appeared between PM2.5 exposure and increased risk of autoimmune diseases.

However, in an adjusted model, chronic exposure to PM10 above 30 mcg/m³ and to PM2.5 above 20 mcg/m³ were associated with a 12% and 13% higher risk, respectively, of any autoimmune disease. 

Chronic exposure to high levels of PM10 was specifically associated with a higher risk of rheumatoid arthritis, but no other autoimmune diseases. Chronic exposure to high levels of PM2.5 was associated with a higher risk of rheumatoid arthritis, connective tissue diseases, and inflammatory bowel diseases.

In their discussion, the researchers noted that the smaller diameter of PM2.5 molecules fluctuate less in response to rain and other weather, compared with PM10 molecules, which might make them a more accurate predictor of exposure to chronic air pollution.

The study findings were limited by several factors including the observational design, which prohibits the establishment of cause, and a lack of data on the start of symptoms and dates of diagnoses for autoimmune diseases, the researchers noted. Other limitations include the high percentage of older women in the study, which may limit generalizability, and the inability to account for additional personal exposure to pollutants outside of the environmental exposure, they said.

However, the results were strengthened by the large sample size and wide geographic distribution with variable pollution exposure, they said.

“Unfortunately, we were not surprised at all,” by the findings, Dr. Adami said in an interview.

“The biological rationale underpinning our findings is strong. Nevertheless, the magnitude of the effect was overwhelming. In addition, we saw an effect even at threshold of exposure that is widely considered as safe,” Dr. Adami noted.

Clinicians have been taught to consider cigarette smoking or other lifestyle behaviors as major risk factors for the development of several autoimmune diseases, said Dr. Adami. “In the future, we probably should include air pollution exposure as a risk factor as well. Interestingly, there is also accumulating evidence linking acute exposure to environmental air pollution with flares of chronic arthritis,” he said.

“Our study could have direct societal and political consequences,” and might help direct policy makers’ decisions on addressing strategies aimed to reduce fossil emissions, he said. As for additional research, “we certainly need multination studies to confirm our results on a larger scale,” Dr. Adami emphasized. “In addition, it is time to take action and start designing interventions aimed to reduce acute and chronic exposure to air pollution in patients suffering from RMDs.”

Consider the big picture of air quality

The Italian study is especially timely “given our evolving and emerging understanding of environmental risk factors for acute and chronic diseases, which we must first understand before we can address,” said Eileen Barrett, MD, of the University of New Mexico, Albuquerque, in an interview.

“I am largely surprised about the findings, as most physicians aren’t studying ambient air quality and risk for autoimmune disease,” said Dr. Barrett. “More often we think of air quality when we think of risk for respiratory diseases than autoimmune diseases, per se,” she said.

“There are several take-home messages from this study,” said Dr. Barrett. “The first is that we need more research to understand the consequences of air pollutants on health. Second, this study reminds us to think broadly about how air quality and our environment can affect health. And third, all clinicians should be committed to promoting science that can improve public health and reduce death and disability,” she emphasized.

The findings do not specifically reflect associations between pollution and other conditions such as chronic obstructive pulmonary disease and asthma although previous studies have shown an association between asthma and COPD exacerbations and air pollution, Dr. Barrett said.

“Further research will be needed to confirm the associations reported in this study,” Dr. Barrett said.

More research in other countries, including research related to other autoimmune diseases, and with other datasets on population and community level risks from poor air quality, would be helpful, and that information could be used to advise smart public policy, Dr. Barrett added.

Air pollution’s mental health impact

Air pollution’s effects extend beyond physical to the psychological, a new study of depression in teenagers showed. This study was published in Developmental Psychology.

Previous research on the environmental factors associated with depressive symptoms in teens has focused mainly on individual and family level contributors; the impact of the physical environment has not been well studied, the investigators, Erika M. Manczak, PhD, of the University of Denver and colleagues, wrote.

In their paper, the authors found a significant impact of neighborhood ozone exposure on the trajectory of depressive symptoms in teens over a 4-year period.

“Given that inhaling pollution activates biological pathways implicated in the development of depression, including immune, cardiovascular, and neurodevelopmental processes, exposure to ambient air pollution may influence the development and/or trajectory of depressive symptoms in youth,” they said.

The researchers recruited 213 adolescents in the San Francisco Bay area through local advertisements. The participants were aged 9-13 years at baseline, with an average age of 11 years. A total of 121 were female, 47% were white, 8.5% were African American, 12.3% were Asian, 10.4% were nonwhite Latin, and 21.7% were biracial or another ethnicity. The participants self-reported depressive symptoms and other psychopathology symptoms up to three times during the study period. Ozone exposure was calculated based on home addresses.

After controlling for other personal, family, and neighborhood variables, the researchers found that higher levels of ozone exposure were significantly associated with increased depressive symptoms over time, and the slope of trajectory of depressive symptoms became steeper as the ozone levels increased (P less than .001). Ozone did not significantly predict the trajectory of any other psychopathology symptoms.

“The results of this study provide preliminary support for the possibility that ozone is an overlooked contributor to the development or course of youth depressive symptoms,” the researchers wrote in their discussion.

“Interestingly, the association between ozone and symptom trajectories as measured by Anxious/Depressed subscale of the [Youth Self-Report] was not as strong as it was for the [Children’s Depression Inventory-Short Version] or Withdrawn/Depressed scales, suggesting that associations are more robust for behavioral withdrawal symptoms of depression than for other types of symptoms,” they noted.

The study findings were limited by the use of self-reports and by the inability of the study design to show causality, the researchers said. Other limitations include the use of average assessments of ozone that are less precise, lack of assessment of biological pathways for risk, lack of formal psychiatric diagnoses, and the small geographic region included in the study, they said.

However, the results provide preliminary evidence that ozone exposure is a potential contributing factor to depressive symptoms in youth, and serve as a jumping-off point for future research, they noted. Future studies should address changes in systemic inflammation, neurodevelopment, or stress reactivity, as well as concurrent psychosocial or biological factors, and temporal associations between air pollution and mental health symptoms, they concluded.

Environmental factors drive inflammatory responses

Peter L. Loper Jr., MD, considers the findings of the Developmental Psychology study to be unsurprising but important – because air pollution is simply getting worse.

“As the study authors cite, there is sufficient data correlating ozone to negative physical health outcomes in youth, but a paucity of data exploring the impact of poor air quality on mental health outcomes in this demographic,” noted Dr. Loper, of the University of South Carolina, Columbia, in an interview.

“As discussed by the study researchers, any environmental exposure that increases immune-mediated inflammation can result in negative health outcomes. In fact, there is already data to suggest that similar cytokines, or immune cell signalers, that get released by our immune system due to environmental exposures and that contribute to asthma, may also be implicated in depression and other mental health problems,” he noted.

“Just like downstream symptom indicators of physical illnesses such as asthma are secondary to immune-mediated pulmonary inflammation, downstream symptom indicators of mental illness, such as depression, are secondary to immune-mediated neuroinflammation,” Dr. Loper emphasized. “The most well-characterized upstream phenomenon perpetuating the downstream symptom indicators of depression involve neuroinflammatory states due to psychosocial and relational factors such as chronic stress, poor relationships, or substance use. However, any environmental factor that triggers an immune response and inflammation can promote neuroinflammation that manifests as symptoms of mental illness.”

The message for teens with depression and their families is that “we are a product of our environment,” Dr. Loper said. “When our environments are proinflammatory, or cause our immune system to become overactive, then we will develop illness; however, the most potent mediator of inflammation in the brain, and the downstream symptoms of depression, is our relationships with those we love most,” he said.

Dr. Loper suggested research aimed at identifying other sources of immune-mediated inflammation caused by physical environments and better understanding how environmental phenomenon like ozone may compound previously established risk factors for mental illness could be useful.

The RMD Open study received no outside funding, and its authors had no financial conflicts.

The Developmental Psychology study was supported by the National Institute of Mental Health and the Stanford University Precision Health and Integrated Diagnostics Center. The researchers for that report, and Dr. Loper and Dr. Barrett had no conflicts to disclose.

The use of preimplantation genetic tests (PGT) in in vitro fertilization cycles, including tests for nonmedical sex selection, increased significantly in states without mandated insurance coverage, based on data from a study of 300,000 IVF cycles.

Previous studies have shown associations between IVF insurance coverage and various IVF practice patterns, but trends in genetic testing according to state-mandated insurance have not been explored, Bronwyn S. Bedrick, MD, of Johns Hopkins University, Baltimore, and colleagues wrote.

“Preimplantation genetic testing was introduced into clinical practice to prevent transmission of genetic disease and to improve uptake of single embryo transfer, but in the real world there are many potential applications,” corresponding author Emily Jungheim, MD, of Northwestern University, Chicago, said in an interview. “We wanted to know how PGT is being applied given that its use is on the rise.”

In a study published in Obstetrics & Gynecology, the researchers analyzed genetic testing in deidentified autologous, nonbanking IVF cycles from 2014 to 2016 obtained through the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS). The data set included 301,465 IVF cycles and 224,235 unique patients over the 3-year study period. Of these, 78,578 cycles (26%) used PGT, and overall, the proportion of IVF cycles using PGT approximately doubled, from 17% in 2014 to 34% in 2016 – a significant increase over time (risk ratio, 1.37). As of 2021, 13 states had mandates that health insurance include IVF costs.

In states with insurance mandates versus nonmandated states, the proportion of any PGT was 28.8% vs. 19.6%, and the probability was 32% lower in states with mandates (RR. 0.68; P < .001).

Aneuploidy was the most common indication for PGT, and accounted for 60% of the cycles; however, the number of cycles using PGT for elective sex selection increased from 1,314 cycles in 2014 to 2,184 in 2016 (approximately 66% increase).

In a multivariate analysis, IVF cycles for elective sex selection was 56% lower in states with mandates, compared with those without (RR, 0.44; P < .001).

In addition, cycles involving nonmedical sex selection were significantly more likely to result in male offspring, the researchers said.

“The increase in the number of cycles using elective sex selection seen in this study may reflect the growing number of clinics offering [PGT] for nonmedical sex selection as well as increasing public awareness of preimplantation genetic testing,” the researchers wrote.

However, the socioeconomic characteristics of women may play a role in the use of PGT, as those living in states with no mandate must be able pay the cost of IVF procedures, as well as the cost of PGT if desired, they noted.

“Because fertility centers may offer patients the choice to select the sex of their embryo after preimplantation genetic testing, this may in effect permit elective sex selection,” the researchers said. The shift in the male-female sex ratio in these cases “is concerning given the implications for future social demographics as IVF and preimplantation genetic testing utilization increase, and the negative effect outcomes could have on medical insurance policy and allocation of resources for medically indicated IVF and preimplantation genetic testing.”

The study findings were limited by several factors including the lack of clinic identifiers and lack of data characteristics including, race, ethnicity, and previous live births, the researchers noted. Other limitations included a lack of data on the sex preferences of the couple, and whether the sex of the embryo was known, and whether male and female embryos were transferred. Also, no states have mandates to cover PGT, and the limited study period may not generalize to current practices.

However, the study strengths include the large size and comprehensive database, and have implications for future policies and expansion of insurance coverage for infertility treatment and for preventing transmission of genetic diseases, they said.
 

Be mindful of consequences of testing

In an interview, Dr. Jungheim said she was surprised by some of the findings. “I thought we would see that PGT-A utilization was lower in states without mandates given the already high cost of IVF for patients paying out of pocket. I was also surprised to see that more males were born after PGT-A; it suggests that overall, patients using PGT-A favor males.

“For clinicians, we need to be mindful of the long-term impact of our practices,” she emphasized. “Shifting the sex ratio in favor of one sex or the other is an unintended consequence of IVF with PGT-A that can have negative implications for future generations.”

In the study, the researchers proposed a revision to the American Society for Reproductive Medicine Ethics Committee opinion on sex selection to provide guidance in keeping with ASRM’s mission of “accessible, ethical, and quality reproductive care for every person.”

However, “even if the ASRM Ethics Committee Opinion was revised, it’s up to clinicians to decide what they are comfortable with,” said Dr. Jungheim. “When patients are paying out of pocket for expensive treatments that require emotional investment and time, it can be difficult to keep medical decision making strictly evidence based.” Improved insurance coverage and access to fertility care may help with some of these decisions, but more real-world evidence is needed. 
 

Let’s talk about sex (selection)

The study findings are both “novel and sobering,” and enhance the current body of evidence of associations between state insurance mandates and IVF outcomes, Jennifer Eaton, MD, of Brown University, Providence, R.I., wrote in an accompanying editorial.

“The association between mandate status and elective sex selection is particularly eye-opening,” said Dr. Eaton. The overall increased use of PGT for sex selection does not account for sex selection as part of testing for aneuploidy. In fact, “patients with euploid embryos of both sexes are frequently given the opportunity to select which embryo to transfer.”

The current study provides “compelling evidence that it is time to revisit the ethical dilemma of elective sex selection in the United States,” Dr. Eaton emphasized. The current ASRM guidance states that IVF clinics are not obligated to provide or refuse to provide nonmedically indicated methods of sex selection, but in light of the current study and other studies, a revision to the existing ASRM Ethics Committee opinion is needed.

The study received no outside funding. Neither the researchers nor Dr. Eaton had any financial conflicts to disclose.

The use of preimplantation genetic tests (PGT) in in vitro fertilization cycles, including tests for nonmedical sex selection, increased significantly in states without mandated insurance coverage, based on data from a study of 300,000 IVF cycles.

Previous studies have shown associations between IVF insurance coverage and various IVF practice patterns, but trends in genetic testing according to state-mandated insurance have not been explored, Bronwyn S. Bedrick, MD, of Johns Hopkins University, Baltimore, and colleagues wrote.

“Preimplantation genetic testing was introduced into clinical practice to prevent transmission of genetic disease and to improve uptake of single embryo transfer, but in the real world there are many potential applications,” corresponding author Emily Jungheim, MD, of Northwestern University, Chicago, said in an interview. “We wanted to know how PGT is being applied given that its use is on the rise.”

In a study published in Obstetrics & Gynecology, the researchers analyzed genetic testing in deidentified autologous, nonbanking IVF cycles from 2014 to 2016 obtained through the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS). The data set included 301,465 IVF cycles and 224,235 unique patients over the 3-year study period. Of these, 78,578 cycles (26%) used PGT, and overall, the proportion of IVF cycles using PGT approximately doubled, from 17% in 2014 to 34% in 2016 – a significant increase over time (risk ratio, 1.37). As of 2021, 13 states had mandates that health insurance include IVF costs.

In states with insurance mandates versus nonmandated states, the proportion of any PGT was 28.8% vs. 19.6%, and the probability was 32% lower in states with mandates (RR. 0.68; P < .001).

Aneuploidy was the most common indication for PGT, and accounted for 60% of the cycles; however, the number of cycles using PGT for elective sex selection increased from 1,314 cycles in 2014 to 2,184 in 2016 (approximately 66% increase).

In a multivariate analysis, IVF cycles for elective sex selection was 56% lower in states with mandates, compared with those without (RR, 0.44; P < .001).

In addition, cycles involving nonmedical sex selection were significantly more likely to result in male offspring, the researchers said.

“The increase in the number of cycles using elective sex selection seen in this study may reflect the growing number of clinics offering [PGT] for nonmedical sex selection as well as increasing public awareness of preimplantation genetic testing,” the researchers wrote.

However, the socioeconomic characteristics of women may play a role in the use of PGT, as those living in states with no mandate must be able pay the cost of IVF procedures, as well as the cost of PGT if desired, they noted.

“Because fertility centers may offer patients the choice to select the sex of their embryo after preimplantation genetic testing, this may in effect permit elective sex selection,” the researchers said. The shift in the male-female sex ratio in these cases “is concerning given the implications for future social demographics as IVF and preimplantation genetic testing utilization increase, and the negative effect outcomes could have on medical insurance policy and allocation of resources for medically indicated IVF and preimplantation genetic testing.”

The study findings were limited by several factors including the lack of clinic identifiers and lack of data characteristics including, race, ethnicity, and previous live births, the researchers noted. Other limitations included a lack of data on the sex preferences of the couple, and whether the sex of the embryo was known, and whether male and female embryos were transferred. Also, no states have mandates to cover PGT, and the limited study period may not generalize to current practices.

However, the study strengths include the large size and comprehensive database, and have implications for future policies and expansion of insurance coverage for infertility treatment and for preventing transmission of genetic diseases, they said.
 

Be mindful of consequences of testing

In an interview, Dr. Jungheim said she was surprised by some of the findings. “I thought we would see that PGT-A utilization was lower in states without mandates given the already high cost of IVF for patients paying out of pocket. I was also surprised to see that more males were born after PGT-A; it suggests that overall, patients using PGT-A favor males.

“For clinicians, we need to be mindful of the long-term impact of our practices,” she emphasized. “Shifting the sex ratio in favor of one sex or the other is an unintended consequence of IVF with PGT-A that can have negative implications for future generations.”

In the study, the researchers proposed a revision to the American Society for Reproductive Medicine Ethics Committee opinion on sex selection to provide guidance in keeping with ASRM’s mission of “accessible, ethical, and quality reproductive care for every person.”

However, “even if the ASRM Ethics Committee Opinion was revised, it’s up to clinicians to decide what they are comfortable with,” said Dr. Jungheim. “When patients are paying out of pocket for expensive treatments that require emotional investment and time, it can be difficult to keep medical decision making strictly evidence based.” Improved insurance coverage and access to fertility care may help with some of these decisions, but more real-world evidence is needed. 
 

Let’s talk about sex (selection)

The study findings are both “novel and sobering,” and enhance the current body of evidence of associations between state insurance mandates and IVF outcomes, Jennifer Eaton, MD, of Brown University, Providence, R.I., wrote in an accompanying editorial.

“The association between mandate status and elective sex selection is particularly eye-opening,” said Dr. Eaton. The overall increased use of PGT for sex selection does not account for sex selection as part of testing for aneuploidy. In fact, “patients with euploid embryos of both sexes are frequently given the opportunity to select which embryo to transfer.”

The current study provides “compelling evidence that it is time to revisit the ethical dilemma of elective sex selection in the United States,” Dr. Eaton emphasized. The current ASRM guidance states that IVF clinics are not obligated to provide or refuse to provide nonmedically indicated methods of sex selection, but in light of the current study and other studies, a revision to the existing ASRM Ethics Committee opinion is needed.

The study received no outside funding. Neither the researchers nor Dr. Eaton had any financial conflicts to disclose.

The use of preimplantation genetic tests (PGT) in in vitro fertilization cycles, including tests for nonmedical sex selection, increased significantly in states without mandated insurance coverage, based on data from a study of 300,000 IVF cycles.

Previous studies have shown associations between IVF insurance coverage and various IVF practice patterns, but trends in genetic testing according to state-mandated insurance have not been explored, Bronwyn S. Bedrick, MD, of Johns Hopkins University, Baltimore, and colleagues wrote.

“Preimplantation genetic testing was introduced into clinical practice to prevent transmission of genetic disease and to improve uptake of single embryo transfer, but in the real world there are many potential applications,” corresponding author Emily Jungheim, MD, of Northwestern University, Chicago, said in an interview. “We wanted to know how PGT is being applied given that its use is on the rise.”

In a study published in Obstetrics & Gynecology, the researchers analyzed genetic testing in deidentified autologous, nonbanking IVF cycles from 2014 to 2016 obtained through the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS). The data set included 301,465 IVF cycles and 224,235 unique patients over the 3-year study period. Of these, 78,578 cycles (26%) used PGT, and overall, the proportion of IVF cycles using PGT approximately doubled, from 17% in 2014 to 34% in 2016 – a significant increase over time (risk ratio, 1.37). As of 2021, 13 states had mandates that health insurance include IVF costs.

In states with insurance mandates versus nonmandated states, the proportion of any PGT was 28.8% vs. 19.6%, and the probability was 32% lower in states with mandates (RR. 0.68; P < .001).

Aneuploidy was the most common indication for PGT, and accounted for 60% of the cycles; however, the number of cycles using PGT for elective sex selection increased from 1,314 cycles in 2014 to 2,184 in 2016 (approximately 66% increase).

In a multivariate analysis, IVF cycles for elective sex selection was 56% lower in states with mandates, compared with those without (RR, 0.44; P < .001).

In addition, cycles involving nonmedical sex selection were significantly more likely to result in male offspring, the researchers said.

“The increase in the number of cycles using elective sex selection seen in this study may reflect the growing number of clinics offering [PGT] for nonmedical sex selection as well as increasing public awareness of preimplantation genetic testing,” the researchers wrote.

However, the socioeconomic characteristics of women may play a role in the use of PGT, as those living in states with no mandate must be able pay the cost of IVF procedures, as well as the cost of PGT if desired, they noted.

“Because fertility centers may offer patients the choice to select the sex of their embryo after preimplantation genetic testing, this may in effect permit elective sex selection,” the researchers said. The shift in the male-female sex ratio in these cases “is concerning given the implications for future social demographics as IVF and preimplantation genetic testing utilization increase, and the negative effect outcomes could have on medical insurance policy and allocation of resources for medically indicated IVF and preimplantation genetic testing.”

The study findings were limited by several factors including the lack of clinic identifiers and lack of data characteristics including, race, ethnicity, and previous live births, the researchers noted. Other limitations included a lack of data on the sex preferences of the couple, and whether the sex of the embryo was known, and whether male and female embryos were transferred. Also, no states have mandates to cover PGT, and the limited study period may not generalize to current practices.

However, the study strengths include the large size and comprehensive database, and have implications for future policies and expansion of insurance coverage for infertility treatment and for preventing transmission of genetic diseases, they said.
 

Be mindful of consequences of testing

In an interview, Dr. Jungheim said she was surprised by some of the findings. “I thought we would see that PGT-A utilization was lower in states without mandates given the already high cost of IVF for patients paying out of pocket. I was also surprised to see that more males were born after PGT-A; it suggests that overall, patients using PGT-A favor males.

“For clinicians, we need to be mindful of the long-term impact of our practices,” she emphasized. “Shifting the sex ratio in favor of one sex or the other is an unintended consequence of IVF with PGT-A that can have negative implications for future generations.”

In the study, the researchers proposed a revision to the American Society for Reproductive Medicine Ethics Committee opinion on sex selection to provide guidance in keeping with ASRM’s mission of “accessible, ethical, and quality reproductive care for every person.”

However, “even if the ASRM Ethics Committee Opinion was revised, it’s up to clinicians to decide what they are comfortable with,” said Dr. Jungheim. “When patients are paying out of pocket for expensive treatments that require emotional investment and time, it can be difficult to keep medical decision making strictly evidence based.” Improved insurance coverage and access to fertility care may help with some of these decisions, but more real-world evidence is needed. 
 

Let’s talk about sex (selection)

The study findings are both “novel and sobering,” and enhance the current body of evidence of associations between state insurance mandates and IVF outcomes, Jennifer Eaton, MD, of Brown University, Providence, R.I., wrote in an accompanying editorial.

“The association between mandate status and elective sex selection is particularly eye-opening,” said Dr. Eaton. The overall increased use of PGT for sex selection does not account for sex selection as part of testing for aneuploidy. In fact, “patients with euploid embryos of both sexes are frequently given the opportunity to select which embryo to transfer.”

The current study provides “compelling evidence that it is time to revisit the ethical dilemma of elective sex selection in the United States,” Dr. Eaton emphasized. The current ASRM guidance states that IVF clinics are not obligated to provide or refuse to provide nonmedically indicated methods of sex selection, but in light of the current study and other studies, a revision to the existing ASRM Ethics Committee opinion is needed.

The study received no outside funding. Neither the researchers nor Dr. Eaton had any financial conflicts to disclose.

More than half of research on homeopathic remedies is unpublished or unregistered, according to a new analysis.

Homeopathy is a form of alternative medicine based on the concept that increasing dilution of a substance leads to a stronger treatment effect.

The authors of the new paper, published in BMJ Evidence-Based Medicine, also found that a quarter of the 90 randomized published trials on homeopathic remedies they analyzed changed their results before publication.

The benefits of homeopathy touted in studies may be greatly exaggerated, suggest the authors, Gerald Gartlehner, MD, of Danube University, Krems, Austria, and colleagues.

The results raise awareness that published homeopathy trials represent a limited proportion of research, skewed toward favorable results, they wrote.

“This likely affects the validity of the body of evidence of homeopathic literature and may substantially overestimate the true treatment effect of homeopathic remedies,” they concluded.

Homeopathy as practiced today was developed approximately 200 years ago in Germany, and despite ongoing debate about its effectiveness, it remains a popular alternative to conventional medicine in many developed countries, the authors noted.

According to the National Institutes of Health, homeopathy is based on the idea of “like cures like,” meaning that a disease can be cured with a substance that produces similar symptoms in healthy people, and the “law of minimum dose,” meaning that a lower dose of medication will be more effective. “Many homeopathic products are so diluted that no molecules of the original substance remain,” according to the NIH.

Homeopathy is not subject to most regulatory requirements, so assessment of effectiveness of homeopathic remedies is limited to published data, the researchers said. “When no information is publicly available about the majority of homeopathic trials, sound conclusions about the efficacy and the risks of using homeopathic medicinal products for treating health conditions are impossible,” they wrote.
 

Study methods and findings

The researchers examined 17 trial registries for studies involving homeopathic remedies conducted since 2002.

The registries included clinicaltrials.gov, the EU Clinical Trials Register, and the International Clinical Trials Registry Platform up to April 2019 to identify registered homeopathy trials.

To determine whether registered trials were published and to identify trials that were published but unregistered, the researchers examined PubMed, the Allied and Complementary Medicine Database, Embase, and Google Scholar up to April 2021.

They found that approximately 38% of registered trials of homeopathy were never published, and 53% of the published randomized, controlled trials (RCTs) were not registered. Notably, 25% of the trials that were registered and published showed primary outcomes that were changed compared with the registry.

The number of registered homeopathy trials increased significantly over the past 5 years, but approximately one-third (30%) of trials published during the last 5 years were not registered, they said. In a meta-analysis, unregistered RCTs showed significantly greater treatment effects than registered RCTs, with standardized mean differences of –0.53 and –0.14, respectively.

The study findings were limited by several factors including the potential for missed records of studies not covered by the registries searched. Other limitations include the analysis of pooled data from homeopathic treatments that may not generalize to personalized homeopathy, and the exclusion of trials labeled as terminated or suspended.
 

Proceed with caution before recommending use of homeopathic remedies, says expert

Linda Girgis, MD, noted that prior to reading this report she had known that most homeopathic remedies didn’t have any evidence of being effective, and that, therefore, the results validated her understanding of the findings of studies of homeopathy.

The study is especially important at this time in the wake of the COVID-19 pandemic, Dr. Girgis, a family physician in private practice in South River, N.J., said in an interview.

“Many people are promoting treatments that don’t have any evidence that they are effective, and more people are turning to homeopathic treatments not knowing the risks and assuming they are safe,” she continued. “Many people are taking advantage of this and trying to cash in on this with ill-proven remedies.”

Homeopathic remedies become especially harmful when patients think they can use them instead of traditional medicine, she added.

Noting that some homeopathic remedies have been studied and show some evidence that they work, Dr. Girgis said there may be a role for certain ones in primary care.

“An example would be black cohosh or primrose oil for perimenopausal hot flashes. This could be a good alternative when you want to avoid hormonal supplements,” she said.

At the same time, Dr. Girgis advised clinicians to be cautious about suggesting homeopathic remedies to patients.

“Homeopathy seems to be a good money maker if you sell these products. However, you are not protected from liability and can be found more liable for prescribing off-label treatments or those not [Food and Drug Administration] approved,” Dr. Girgis said. Her general message to clinicians: Stick with evidence-based medicine.

Her message to patients who might want to pursue homeopathic remedies is that just because something is “homeopathic” or natural doesn’t mean that it is safe.

“There are some [homeopathic] products that have caused liver damage or other problems,” she explained. “Also, these remedies can interact with other medications.”

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

More than half of research on homeopathic remedies is unpublished or unregistered, according to a new analysis.

Homeopathy is a form of alternative medicine based on the concept that increasing dilution of a substance leads to a stronger treatment effect.

The authors of the new paper, published in BMJ Evidence-Based Medicine, also found that a quarter of the 90 randomized published trials on homeopathic remedies they analyzed changed their results before publication.

The benefits of homeopathy touted in studies may be greatly exaggerated, suggest the authors, Gerald Gartlehner, MD, of Danube University, Krems, Austria, and colleagues.

The results raise awareness that published homeopathy trials represent a limited proportion of research, skewed toward favorable results, they wrote.

“This likely affects the validity of the body of evidence of homeopathic literature and may substantially overestimate the true treatment effect of homeopathic remedies,” they concluded.

Homeopathy as practiced today was developed approximately 200 years ago in Germany, and despite ongoing debate about its effectiveness, it remains a popular alternative to conventional medicine in many developed countries, the authors noted.

According to the National Institutes of Health, homeopathy is based on the idea of “like cures like,” meaning that a disease can be cured with a substance that produces similar symptoms in healthy people, and the “law of minimum dose,” meaning that a lower dose of medication will be more effective. “Many homeopathic products are so diluted that no molecules of the original substance remain,” according to the NIH.

Homeopathy is not subject to most regulatory requirements, so assessment of effectiveness of homeopathic remedies is limited to published data, the researchers said. “When no information is publicly available about the majority of homeopathic trials, sound conclusions about the efficacy and the risks of using homeopathic medicinal products for treating health conditions are impossible,” they wrote.
 

Study methods and findings

The researchers examined 17 trial registries for studies involving homeopathic remedies conducted since 2002.

The registries included clinicaltrials.gov, the EU Clinical Trials Register, and the International Clinical Trials Registry Platform up to April 2019 to identify registered homeopathy trials.

To determine whether registered trials were published and to identify trials that were published but unregistered, the researchers examined PubMed, the Allied and Complementary Medicine Database, Embase, and Google Scholar up to April 2021.

They found that approximately 38% of registered trials of homeopathy were never published, and 53% of the published randomized, controlled trials (RCTs) were not registered. Notably, 25% of the trials that were registered and published showed primary outcomes that were changed compared with the registry.

The number of registered homeopathy trials increased significantly over the past 5 years, but approximately one-third (30%) of trials published during the last 5 years were not registered, they said. In a meta-analysis, unregistered RCTs showed significantly greater treatment effects than registered RCTs, with standardized mean differences of –0.53 and –0.14, respectively.

The study findings were limited by several factors including the potential for missed records of studies not covered by the registries searched. Other limitations include the analysis of pooled data from homeopathic treatments that may not generalize to personalized homeopathy, and the exclusion of trials labeled as terminated or suspended.
 

Proceed with caution before recommending use of homeopathic remedies, says expert

Linda Girgis, MD, noted that prior to reading this report she had known that most homeopathic remedies didn’t have any evidence of being effective, and that, therefore, the results validated her understanding of the findings of studies of homeopathy.

The study is especially important at this time in the wake of the COVID-19 pandemic, Dr. Girgis, a family physician in private practice in South River, N.J., said in an interview.

“Many people are promoting treatments that don’t have any evidence that they are effective, and more people are turning to homeopathic treatments not knowing the risks and assuming they are safe,” she continued. “Many people are taking advantage of this and trying to cash in on this with ill-proven remedies.”

Homeopathic remedies become especially harmful when patients think they can use them instead of traditional medicine, she added.

Noting that some homeopathic remedies have been studied and show some evidence that they work, Dr. Girgis said there may be a role for certain ones in primary care.

“An example would be black cohosh or primrose oil for perimenopausal hot flashes. This could be a good alternative when you want to avoid hormonal supplements,” she said.

At the same time, Dr. Girgis advised clinicians to be cautious about suggesting homeopathic remedies to patients.

“Homeopathy seems to be a good money maker if you sell these products. However, you are not protected from liability and can be found more liable for prescribing off-label treatments or those not [Food and Drug Administration] approved,” Dr. Girgis said. Her general message to clinicians: Stick with evidence-based medicine.

Her message to patients who might want to pursue homeopathic remedies is that just because something is “homeopathic” or natural doesn’t mean that it is safe.

“There are some [homeopathic] products that have caused liver damage or other problems,” she explained. “Also, these remedies can interact with other medications.”

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

More than half of research on homeopathic remedies is unpublished or unregistered, according to a new analysis.

Homeopathy is a form of alternative medicine based on the concept that increasing dilution of a substance leads to a stronger treatment effect.

The authors of the new paper, published in BMJ Evidence-Based Medicine, also found that a quarter of the 90 randomized published trials on homeopathic remedies they analyzed changed their results before publication.

The benefits of homeopathy touted in studies may be greatly exaggerated, suggest the authors, Gerald Gartlehner, MD, of Danube University, Krems, Austria, and colleagues.

The results raise awareness that published homeopathy trials represent a limited proportion of research, skewed toward favorable results, they wrote.

“This likely affects the validity of the body of evidence of homeopathic literature and may substantially overestimate the true treatment effect of homeopathic remedies,” they concluded.

Homeopathy as practiced today was developed approximately 200 years ago in Germany, and despite ongoing debate about its effectiveness, it remains a popular alternative to conventional medicine in many developed countries, the authors noted.

According to the National Institutes of Health, homeopathy is based on the idea of “like cures like,” meaning that a disease can be cured with a substance that produces similar symptoms in healthy people, and the “law of minimum dose,” meaning that a lower dose of medication will be more effective. “Many homeopathic products are so diluted that no molecules of the original substance remain,” according to the NIH.

Homeopathy is not subject to most regulatory requirements, so assessment of effectiveness of homeopathic remedies is limited to published data, the researchers said. “When no information is publicly available about the majority of homeopathic trials, sound conclusions about the efficacy and the risks of using homeopathic medicinal products for treating health conditions are impossible,” they wrote.
 

Study methods and findings

The researchers examined 17 trial registries for studies involving homeopathic remedies conducted since 2002.

The registries included clinicaltrials.gov, the EU Clinical Trials Register, and the International Clinical Trials Registry Platform up to April 2019 to identify registered homeopathy trials.

To determine whether registered trials were published and to identify trials that were published but unregistered, the researchers examined PubMed, the Allied and Complementary Medicine Database, Embase, and Google Scholar up to April 2021.

They found that approximately 38% of registered trials of homeopathy were never published, and 53% of the published randomized, controlled trials (RCTs) were not registered. Notably, 25% of the trials that were registered and published showed primary outcomes that were changed compared with the registry.

The number of registered homeopathy trials increased significantly over the past 5 years, but approximately one-third (30%) of trials published during the last 5 years were not registered, they said. In a meta-analysis, unregistered RCTs showed significantly greater treatment effects than registered RCTs, with standardized mean differences of –0.53 and –0.14, respectively.

The study findings were limited by several factors including the potential for missed records of studies not covered by the registries searched. Other limitations include the analysis of pooled data from homeopathic treatments that may not generalize to personalized homeopathy, and the exclusion of trials labeled as terminated or suspended.
 

Proceed with caution before recommending use of homeopathic remedies, says expert

Linda Girgis, MD, noted that prior to reading this report she had known that most homeopathic remedies didn’t have any evidence of being effective, and that, therefore, the results validated her understanding of the findings of studies of homeopathy.

The study is especially important at this time in the wake of the COVID-19 pandemic, Dr. Girgis, a family physician in private practice in South River, N.J., said in an interview.

“Many people are promoting treatments that don’t have any evidence that they are effective, and more people are turning to homeopathic treatments not knowing the risks and assuming they are safe,” she continued. “Many people are taking advantage of this and trying to cash in on this with ill-proven remedies.”

Homeopathic remedies become especially harmful when patients think they can use them instead of traditional medicine, she added.

Noting that some homeopathic remedies have been studied and show some evidence that they work, Dr. Girgis said there may be a role for certain ones in primary care.

“An example would be black cohosh or primrose oil for perimenopausal hot flashes. This could be a good alternative when you want to avoid hormonal supplements,” she said.

At the same time, Dr. Girgis advised clinicians to be cautious about suggesting homeopathic remedies to patients.

“Homeopathy seems to be a good money maker if you sell these products. However, you are not protected from liability and can be found more liable for prescribing off-label treatments or those not [Food and Drug Administration] approved,” Dr. Girgis said. Her general message to clinicians: Stick with evidence-based medicine.

Her message to patients who might want to pursue homeopathic remedies is that just because something is “homeopathic” or natural doesn’t mean that it is safe.

“There are some [homeopathic] products that have caused liver damage or other problems,” she explained. “Also, these remedies can interact with other medications.”

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

Most lung cancer patients with interstitial lung disease will not benefit from thoracic radiotherapy, based on data from a systematic review of 24 studies.

Thoracic radiotherapy remains a key part of lung cancer treatment for early and metastatic disease. However, patients with both small cell lung cancer (SCLC) and non–small cell lung cancer (NSCLC) associated with interstitial lung disease (ILD) fare worse than do those without ILD, often because of acute exacerbation of ILD and severe or fatal pneumonitis, wrote Animesh Saha, MD, of Apollo Multi-Specialty Hospitals, Kolkata, India, and colleagues. Consequently, clinicians may hesitate to offer radiotherapy to these patients.

In a review published in Clinical Oncology, the researchers identified 24 studies, including phase II and phase III randomized or nonrandomized trials, as well as prospective, observational studies and retrospective real-world studies. The goal of the review was to report the incidence and predictors of radiation pneumonitis associated with different types of thoracic radiotherapy for lung cancer patients with ILD, the researchers said. Treatment types included curative-intent fractionated radiotherapy or chemoradiotherapy or moderately hypofractionated (nonstereotactic ablative radiotherapy [SABR]) and hyperfractionated radiotherapy as well as particle beam therapies.

The studies included patients with SCLC or NSCLC and any form of ILD, including subclinical, radiologically diagnosed, or symptomatic, the researchers said.

Overall, the median incidence of grade 3 or higher radiation pneumonitis was 19.7%; the median incidence in patients treated with conventional radical radiotherapy, SABR, and particle beam therapy was 31.8%, 11.9%, and 20.25%, respectively.

Eighteen studies reported grade 5 radiation pneumonitis; the overall median incidence was 6%, but as high as 60% in some studies. When separated by treatment type, the median incidence was 2.7%, 6.25%, and 6.25%, respectively, in patients treated with radical radiotherapy (non-SABR), SABR, and particle beam therapy.

Independent predictors of severe radiation pneumonitis (grade 2 or higher and grade 3 or higher) included subclinical or radiological ILD, the researchers said. Among ILD subtypes, studies have shown increased risk for severe radiation pneumonitis among those with non-IPF or non-UIP pattern fibrosis.

In addition, patient-related factors of low forced vital capacity (FVC) and low forced expiratory volume in 1 second (FEV₁), have been associated with severe radiation pneumonitis, the researchers said. They also found increased risk for patients with lower lobe tumor location compared to other lobes.

As for treatment-related factors, a history of gemcitabine chemotherapy was associated with an increased risk of grade 3 or higher radiation pneumonitis.

“There is always concern about using thoracic radiotherapy in lung cancer patients with coexisting ILD in view of the risks involved,” the researchers wrote in their discussion of the findings. “Although thoracic radiotherapy is expected to produce similar local control, overall survival is worse in lung cancer patients with ILD than without, probably due to the poor prognosis associated with ILD and associated treatment-related mortality,” they said.

The findings were limited by several factors including the heterogeneity of the studies and study population and the retrospective design of most of the studies, the researchers noted.

However, the results highlight the increased risk of severe and fatal radiation pneumonitis in lung cancer patients with ILD and the need for careful patient selection and counseling if thoracic radiotherapy is to be considered, they concluded.

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

Most lung cancer patients with interstitial lung disease will not benefit from thoracic radiotherapy, based on data from a systematic review of 24 studies.

Thoracic radiotherapy remains a key part of lung cancer treatment for early and metastatic disease. However, patients with both small cell lung cancer (SCLC) and non–small cell lung cancer (NSCLC) associated with interstitial lung disease (ILD) fare worse than do those without ILD, often because of acute exacerbation of ILD and severe or fatal pneumonitis, wrote Animesh Saha, MD, of Apollo Multi-Specialty Hospitals, Kolkata, India, and colleagues. Consequently, clinicians may hesitate to offer radiotherapy to these patients.

In a review published in Clinical Oncology, the researchers identified 24 studies, including phase II and phase III randomized or nonrandomized trials, as well as prospective, observational studies and retrospective real-world studies. The goal of the review was to report the incidence and predictors of radiation pneumonitis associated with different types of thoracic radiotherapy for lung cancer patients with ILD, the researchers said. Treatment types included curative-intent fractionated radiotherapy or chemoradiotherapy or moderately hypofractionated (nonstereotactic ablative radiotherapy [SABR]) and hyperfractionated radiotherapy as well as particle beam therapies.

The studies included patients with SCLC or NSCLC and any form of ILD, including subclinical, radiologically diagnosed, or symptomatic, the researchers said.

Overall, the median incidence of grade 3 or higher radiation pneumonitis was 19.7%; the median incidence in patients treated with conventional radical radiotherapy, SABR, and particle beam therapy was 31.8%, 11.9%, and 20.25%, respectively.

Eighteen studies reported grade 5 radiation pneumonitis; the overall median incidence was 6%, but as high as 60% in some studies. When separated by treatment type, the median incidence was 2.7%, 6.25%, and 6.25%, respectively, in patients treated with radical radiotherapy (non-SABR), SABR, and particle beam therapy.

Independent predictors of severe radiation pneumonitis (grade 2 or higher and grade 3 or higher) included subclinical or radiological ILD, the researchers said. Among ILD subtypes, studies have shown increased risk for severe radiation pneumonitis among those with non-IPF or non-UIP pattern fibrosis.

In addition, patient-related factors of low forced vital capacity (FVC) and low forced expiratory volume in 1 second (FEV₁), have been associated with severe radiation pneumonitis, the researchers said. They also found increased risk for patients with lower lobe tumor location compared to other lobes.

As for treatment-related factors, a history of gemcitabine chemotherapy was associated with an increased risk of grade 3 or higher radiation pneumonitis.

“There is always concern about using thoracic radiotherapy in lung cancer patients with coexisting ILD in view of the risks involved,” the researchers wrote in their discussion of the findings. “Although thoracic radiotherapy is expected to produce similar local control, overall survival is worse in lung cancer patients with ILD than without, probably due to the poor prognosis associated with ILD and associated treatment-related mortality,” they said.

The findings were limited by several factors including the heterogeneity of the studies and study population and the retrospective design of most of the studies, the researchers noted.

However, the results highlight the increased risk of severe and fatal radiation pneumonitis in lung cancer patients with ILD and the need for careful patient selection and counseling if thoracic radiotherapy is to be considered, they concluded.

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

Most lung cancer patients with interstitial lung disease will not benefit from thoracic radiotherapy, based on data from a systematic review of 24 studies.

Thoracic radiotherapy remains a key part of lung cancer treatment for early and metastatic disease. However, patients with both small cell lung cancer (SCLC) and non–small cell lung cancer (NSCLC) associated with interstitial lung disease (ILD) fare worse than do those without ILD, often because of acute exacerbation of ILD and severe or fatal pneumonitis, wrote Animesh Saha, MD, of Apollo Multi-Specialty Hospitals, Kolkata, India, and colleagues. Consequently, clinicians may hesitate to offer radiotherapy to these patients.

In a review published in Clinical Oncology, the researchers identified 24 studies, including phase II and phase III randomized or nonrandomized trials, as well as prospective, observational studies and retrospective real-world studies. The goal of the review was to report the incidence and predictors of radiation pneumonitis associated with different types of thoracic radiotherapy for lung cancer patients with ILD, the researchers said. Treatment types included curative-intent fractionated radiotherapy or chemoradiotherapy or moderately hypofractionated (nonstereotactic ablative radiotherapy [SABR]) and hyperfractionated radiotherapy as well as particle beam therapies.

The studies included patients with SCLC or NSCLC and any form of ILD, including subclinical, radiologically diagnosed, or symptomatic, the researchers said.

Overall, the median incidence of grade 3 or higher radiation pneumonitis was 19.7%; the median incidence in patients treated with conventional radical radiotherapy, SABR, and particle beam therapy was 31.8%, 11.9%, and 20.25%, respectively.

Eighteen studies reported grade 5 radiation pneumonitis; the overall median incidence was 6%, but as high as 60% in some studies. When separated by treatment type, the median incidence was 2.7%, 6.25%, and 6.25%, respectively, in patients treated with radical radiotherapy (non-SABR), SABR, and particle beam therapy.

Independent predictors of severe radiation pneumonitis (grade 2 or higher and grade 3 or higher) included subclinical or radiological ILD, the researchers said. Among ILD subtypes, studies have shown increased risk for severe radiation pneumonitis among those with non-IPF or non-UIP pattern fibrosis.

In addition, patient-related factors of low forced vital capacity (FVC) and low forced expiratory volume in 1 second (FEV₁), have been associated with severe radiation pneumonitis, the researchers said. They also found increased risk for patients with lower lobe tumor location compared to other lobes.

As for treatment-related factors, a history of gemcitabine chemotherapy was associated with an increased risk of grade 3 or higher radiation pneumonitis.

“There is always concern about using thoracic radiotherapy in lung cancer patients with coexisting ILD in view of the risks involved,” the researchers wrote in their discussion of the findings. “Although thoracic radiotherapy is expected to produce similar local control, overall survival is worse in lung cancer patients with ILD than without, probably due to the poor prognosis associated with ILD and associated treatment-related mortality,” they said.

The findings were limited by several factors including the heterogeneity of the studies and study population and the retrospective design of most of the studies, the researchers noted.

However, the results highlight the increased risk of severe and fatal radiation pneumonitis in lung cancer patients with ILD and the need for careful patient selection and counseling if thoracic radiotherapy is to be considered, they concluded.

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

Endoscopic submucosal dissection to remove large colorectal lesions was performed safely and successfully in an outpatient setting, based on data from more than 600 patients.

The widespread adoption of endoscopic submucosal dissection (ESD) has been slow because of its relative complexity, compared with other procedures, wrote Viktor Tidehag, MD, of Danderyd Hospital, Stockholm, and colleagues. The technique, first developed in Japan, is usually an inpatient procedure in Asian countries, the researchers said. However, “We have previously published a study of 156 ESD patients discharged after 2-4 hours of observation post ESD, providing a proof of concept that uncomplicated colorectal ESD can be safely performed as an outpatient procedure,” they wrote.

ChrisChrisW/iStock/Getty Images

In a study published in Gastrointestinal Endoscopy, the researchers reviewed data from a larger group of 660 consecutive colorectal ESD procedures at a single center between April 2014 and November 2020. Of these, 48 were planned admission and 612 were scheduled as outpatient procedures. All patients had lesions greater than 20 mm; the median size of the lesions was 38 mm, but the median lesion size was significantly smaller for outpatients, compared with inpatients (37 mm vs. 55 mm). The lesions included 323 (48.9%) in the proximal colon, 102 (15.5%) in the distal colon, and 235 (35.6%) in the rectum. The median procedure duration was 70 minutes, but was significantly shorter for outpatients, compared with inpatients (65 minutes vs. 121 minutes). The mean age of patients in the outpatient and inpatient groups was 68.7 years vs. 70.6 years.

Overall, en bloc resection was achieved in 620 (93.9%) cases, 30 were completed as piecemeal resections, and 10 were aborted and referred for surgical resection. A total of 33 of the scheduled outpatient procedures turned into unplanned inpatient procedures.

As for intraoperative adverse events, no significant differences in perforation rate occurred between inpatients and outpatients. Overall, perforation occurred in 38 cases (5.8%); 35 of these were treated with clip and 21 also were treated with antibiotics. A total of three patients required emergency surgery following perforations.

Within 30 days of the procedures, 46 patients (7.0%) sought medical attention for possible procedure-related concerns, the researchers said. “No correlation was found between 30-day complications and lesion location, resection speed, age, or perioperative perforation,” the researchers wrote in their discussion of the findings.

The study findings were limited by several factors including the retrospective, nonrandomized design from a single center, with no controls, as well as the potential for selection bias of healthy patients selected for outpatient procedures, and lack of data on comorbidities, the researchers noted. However, the results were strengthened by the inclusion of a large number of lesions in the proximal colon, they said.

Endoscopic treatment is associated with lower mortality and morbidity, as well as lower costs, compared with laparoscopic and open surgery, and ESD could have a significant effect on health economics if widely implemented, the researchers noted in their discussion. “Being able to perform ESD in an outpatient setting compared to an inpatient situation would further decrease treatment costs compared to resection surgery,” they said. However, “patients must be well informed about the anticipated postoperative course and potential complications that can arise,” particularly in relation to intraprocedural or delayed perforation, they concluded.

Data support adoption of ESD

The current study was informative and will provide more support for adoption of colorectal ESD in the West, said Salmaan Jawaid, MD, of Baylor College of Medicine, Houston, in an interview.

“Health economics in Asian countries are strikingly different than in other countries and support routine postprocedural admissions for observation,” Dr. Jawaid said. “Colorectal ESD has been slow to gain momentum in the West due to a steep learning curve, long procedural times, and the potential for complications with resultant hospital admissions. These logistical elements and impact on health care economics in the West serve as tremendous deterrents [of] adoption of colorectal ESD,” he explained.

“The current study demonstrates colorectal ESD, in a European health care system, may be feasible and safe in an outpatient setting, thereby effectively utilizing health care resources,” said Dr. Jawaid. “If admission after colorectal ESD is not routinely needed, health care systems may be more willing to support ESD on a broader scale with a consequent increase in surgery-saving procedures,” he noted.

Dr. Jawaid said he was not surprised by the findings overall. “However, I did find it interesting the number of patients who were safely discharged the same day after suffering colonic perforations,” he noted. He suspects improved methods of defect closure would explain this, and could in turn increase the rate of adoption.

“In experienced hands, I believe similar results will be attainable in a U.S.-based health care system,” he added.

However, “Validated protocol-based clinical pathways are needed in the West before widespread outpatient colorectal ESD is implemented. In the United States, emphasis should be made on the development of long-term educational systems whose primary goal is to ensure proper skills are acquired for endoscopic dissection,” he emphasized. “If support from a U.S. health care system is desired on a larger scale, detailed cost-benefit analyses are needed comparing all modalities of colon polyp removal.” 

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Jawaid disclosed serving as a consultant for Lumendi and Conmed.

This article was updated March 15, 2022.

Endoscopic submucosal dissection to remove large colorectal lesions was performed safely and successfully in an outpatient setting, based on data from more than 600 patients.

The widespread adoption of endoscopic submucosal dissection (ESD) has been slow because of its relative complexity, compared with other procedures, wrote Viktor Tidehag, MD, of Danderyd Hospital, Stockholm, and colleagues. The technique, first developed in Japan, is usually an inpatient procedure in Asian countries, the researchers said. However, “We have previously published a study of 156 ESD patients discharged after 2-4 hours of observation post ESD, providing a proof of concept that uncomplicated colorectal ESD can be safely performed as an outpatient procedure,” they wrote.

ChrisChrisW/iStock/Getty Images

In a study published in Gastrointestinal Endoscopy, the researchers reviewed data from a larger group of 660 consecutive colorectal ESD procedures at a single center between April 2014 and November 2020. Of these, 48 were planned admission and 612 were scheduled as outpatient procedures. All patients had lesions greater than 20 mm; the median size of the lesions was 38 mm, but the median lesion size was significantly smaller for outpatients, compared with inpatients (37 mm vs. 55 mm). The lesions included 323 (48.9%) in the proximal colon, 102 (15.5%) in the distal colon, and 235 (35.6%) in the rectum. The median procedure duration was 70 minutes, but was significantly shorter for outpatients, compared with inpatients (65 minutes vs. 121 minutes). The mean age of patients in the outpatient and inpatient groups was 68.7 years vs. 70.6 years.

Overall, en bloc resection was achieved in 620 (93.9%) cases, 30 were completed as piecemeal resections, and 10 were aborted and referred for surgical resection. A total of 33 of the scheduled outpatient procedures turned into unplanned inpatient procedures.

As for intraoperative adverse events, no significant differences in perforation rate occurred between inpatients and outpatients. Overall, perforation occurred in 38 cases (5.8%); 35 of these were treated with clip and 21 also were treated with antibiotics. A total of three patients required emergency surgery following perforations.

Within 30 days of the procedures, 46 patients (7.0%) sought medical attention for possible procedure-related concerns, the researchers said. “No correlation was found between 30-day complications and lesion location, resection speed, age, or perioperative perforation,” the researchers wrote in their discussion of the findings.

The study findings were limited by several factors including the retrospective, nonrandomized design from a single center, with no controls, as well as the potential for selection bias of healthy patients selected for outpatient procedures, and lack of data on comorbidities, the researchers noted. However, the results were strengthened by the inclusion of a large number of lesions in the proximal colon, they said.

Endoscopic treatment is associated with lower mortality and morbidity, as well as lower costs, compared with laparoscopic and open surgery, and ESD could have a significant effect on health economics if widely implemented, the researchers noted in their discussion. “Being able to perform ESD in an outpatient setting compared to an inpatient situation would further decrease treatment costs compared to resection surgery,” they said. However, “patients must be well informed about the anticipated postoperative course and potential complications that can arise,” particularly in relation to intraprocedural or delayed perforation, they concluded.

Data support adoption of ESD

The current study was informative and will provide more support for adoption of colorectal ESD in the West, said Salmaan Jawaid, MD, of Baylor College of Medicine, Houston, in an interview.

“Health economics in Asian countries are strikingly different than in other countries and support routine postprocedural admissions for observation,” Dr. Jawaid said. “Colorectal ESD has been slow to gain momentum in the West due to a steep learning curve, long procedural times, and the potential for complications with resultant hospital admissions. These logistical elements and impact on health care economics in the West serve as tremendous deterrents [of] adoption of colorectal ESD,” he explained.

“The current study demonstrates colorectal ESD, in a European health care system, may be feasible and safe in an outpatient setting, thereby effectively utilizing health care resources,” said Dr. Jawaid. “If admission after colorectal ESD is not routinely needed, health care systems may be more willing to support ESD on a broader scale with a consequent increase in surgery-saving procedures,” he noted.

Dr. Jawaid said he was not surprised by the findings overall. “However, I did find it interesting the number of patients who were safely discharged the same day after suffering colonic perforations,” he noted. He suspects improved methods of defect closure would explain this, and could in turn increase the rate of adoption.

“In experienced hands, I believe similar results will be attainable in a U.S.-based health care system,” he added.

However, “Validated protocol-based clinical pathways are needed in the West before widespread outpatient colorectal ESD is implemented. In the United States, emphasis should be made on the development of long-term educational systems whose primary goal is to ensure proper skills are acquired for endoscopic dissection,” he emphasized. “If support from a U.S. health care system is desired on a larger scale, detailed cost-benefit analyses are needed comparing all modalities of colon polyp removal.” 

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Jawaid disclosed serving as a consultant for Lumendi and Conmed.

This article was updated March 15, 2022.

Endoscopic submucosal dissection to remove large colorectal lesions was performed safely and successfully in an outpatient setting, based on data from more than 600 patients.

The widespread adoption of endoscopic submucosal dissection (ESD) has been slow because of its relative complexity, compared with other procedures, wrote Viktor Tidehag, MD, of Danderyd Hospital, Stockholm, and colleagues. The technique, first developed in Japan, is usually an inpatient procedure in Asian countries, the researchers said. However, “We have previously published a study of 156 ESD patients discharged after 2-4 hours of observation post ESD, providing a proof of concept that uncomplicated colorectal ESD can be safely performed as an outpatient procedure,” they wrote.

ChrisChrisW/iStock/Getty Images

In a study published in Gastrointestinal Endoscopy, the researchers reviewed data from a larger group of 660 consecutive colorectal ESD procedures at a single center between April 2014 and November 2020. Of these, 48 were planned admission and 612 were scheduled as outpatient procedures. All patients had lesions greater than 20 mm; the median size of the lesions was 38 mm, but the median lesion size was significantly smaller for outpatients, compared with inpatients (37 mm vs. 55 mm). The lesions included 323 (48.9%) in the proximal colon, 102 (15.5%) in the distal colon, and 235 (35.6%) in the rectum. The median procedure duration was 70 minutes, but was significantly shorter for outpatients, compared with inpatients (65 minutes vs. 121 minutes). The mean age of patients in the outpatient and inpatient groups was 68.7 years vs. 70.6 years.

Overall, en bloc resection was achieved in 620 (93.9%) cases, 30 were completed as piecemeal resections, and 10 were aborted and referred for surgical resection. A total of 33 of the scheduled outpatient procedures turned into unplanned inpatient procedures.

As for intraoperative adverse events, no significant differences in perforation rate occurred between inpatients and outpatients. Overall, perforation occurred in 38 cases (5.8%); 35 of these were treated with clip and 21 also were treated with antibiotics. A total of three patients required emergency surgery following perforations.

Within 30 days of the procedures, 46 patients (7.0%) sought medical attention for possible procedure-related concerns, the researchers said. “No correlation was found between 30-day complications and lesion location, resection speed, age, or perioperative perforation,” the researchers wrote in their discussion of the findings.

The study findings were limited by several factors including the retrospective, nonrandomized design from a single center, with no controls, as well as the potential for selection bias of healthy patients selected for outpatient procedures, and lack of data on comorbidities, the researchers noted. However, the results were strengthened by the inclusion of a large number of lesions in the proximal colon, they said.

Endoscopic treatment is associated with lower mortality and morbidity, as well as lower costs, compared with laparoscopic and open surgery, and ESD could have a significant effect on health economics if widely implemented, the researchers noted in their discussion. “Being able to perform ESD in an outpatient setting compared to an inpatient situation would further decrease treatment costs compared to resection surgery,” they said. However, “patients must be well informed about the anticipated postoperative course and potential complications that can arise,” particularly in relation to intraprocedural or delayed perforation, they concluded.

Data support adoption of ESD

The current study was informative and will provide more support for adoption of colorectal ESD in the West, said Salmaan Jawaid, MD, of Baylor College of Medicine, Houston, in an interview.

“Health economics in Asian countries are strikingly different than in other countries and support routine postprocedural admissions for observation,” Dr. Jawaid said. “Colorectal ESD has been slow to gain momentum in the West due to a steep learning curve, long procedural times, and the potential for complications with resultant hospital admissions. These logistical elements and impact on health care economics in the West serve as tremendous deterrents [of] adoption of colorectal ESD,” he explained.

“The current study demonstrates colorectal ESD, in a European health care system, may be feasible and safe in an outpatient setting, thereby effectively utilizing health care resources,” said Dr. Jawaid. “If admission after colorectal ESD is not routinely needed, health care systems may be more willing to support ESD on a broader scale with a consequent increase in surgery-saving procedures,” he noted.

Dr. Jawaid said he was not surprised by the findings overall. “However, I did find it interesting the number of patients who were safely discharged the same day after suffering colonic perforations,” he noted. He suspects improved methods of defect closure would explain this, and could in turn increase the rate of adoption.

“In experienced hands, I believe similar results will be attainable in a U.S.-based health care system,” he added.

However, “Validated protocol-based clinical pathways are needed in the West before widespread outpatient colorectal ESD is implemented. In the United States, emphasis should be made on the development of long-term educational systems whose primary goal is to ensure proper skills are acquired for endoscopic dissection,” he emphasized. “If support from a U.S. health care system is desired on a larger scale, detailed cost-benefit analyses are needed comparing all modalities of colon polyp removal.” 

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Jawaid disclosed serving as a consultant for Lumendi and Conmed.

This article was updated March 15, 2022.

Survival rates of biologics and other novel immunomodulatory drugs vary substantially across chronic inflammatory diseases, and rates are highest for rituximab in rheumatoid arthritis (RA) and golimumab in axial spondyloarthritis (axSpA), but with similar rates seen for most drugs used in the treatment of psoriasis and psoriatic arthritis (PsA), according to findings from a study of two Danish registries.

Drug survival refers to “the probability that patients will remain on a given drug, and is a proxy for efficacy as well as safety in daily clinical practice,” wrote Alexander Egeberg, MD, PhD, of the department of dermatology at Copenhagen University Hospital–Bispebjerg, and colleagues. Although the use of biologics has expanded for inflammatory diseases, real-world data on drug survival in newer agents such as interleukin (IL)-17, IL-23, and Janus kinase inhibitors are lacking, they said.

In a study published in Seminars in Arthritis and Rheumatism, the researchers reviewed data from the DANBIO and DERMBIO registries of patients in Denmark with inflammatory diseases including rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis.

The study population included 12,089 adults: 5,104 with RA, 2,157 with AxSpA, 2,251 with PsA, and 2,577 with psoriasis. Patients’ mean age at the time of first treatment for these conditions was 57.8 years, 42.3 years, 49 years, and 45 years, respectively. Participants were treated with biologics or novel small molecule therapies for RA, AxSpA, PsA, or psoriasis between January 2015 and May 2021 (from the DANBIO database) and November 2009 to November 2019 (DERMBIO database).

In adjusted models, drug survival in RA was highest for rituximab followed by baricitinib, etanercept, and tocilizumab. Drug survival in AxSpA was highest for golimumab, compared with all other drugs, followed by secukinumab and etanercept. Survival was lowest for infliximab. In PsA, drug survival was roughly equal for most drugs, including golimumab, secukinumab, and ixekizumab, with the lowest survival observed for tofacitinib and infliximab, compared with all other drugs. Drug survival in psoriasis was highest with guselkumab, followed by ustekinumab and IL-17 inhibitors.

However, the number of treatment series “was low for some drugs, and not all differences were statistically significant, which could influence the overall interpretability of these findings,” the researchers noted in their discussion.

Notably, the high treatment persistence for rituximab in RA patients needs further confirmation, the researchers said. “In Denmark, rituximab is often the biologic drug of choice in RA patients with a history of cancer while there is a reluctancy to use TNF [tumor necrosis factor] inhibitors in such patients; this may have prolonged the drug survival for rituximab treated patients due to limited treatment alternatives,” they said.

The findings were limited by several factors, including the observational study design and changes in guidelines over the course of the study, the researchers noted. Other limitations included the inability to adjust for certain variables, such as antibody status, body weight, and smoking, because of missing data, and a lack of data on the underlying reasons for drug discontinuation, they said.

However, the results were strengthened by the large number of patients and completeness of the registries, the researchers emphasized. The range in responses to different drug types across diseases supports the need for individualized treatments with attention to underlying disease, patient profile, and treatment history, they concluded.

The study received no outside funding. Eight coauthors reported financial ties to a number of pharmaceutical companies.

Survival rates of biologics and other novel immunomodulatory drugs vary substantially across chronic inflammatory diseases, and rates are highest for rituximab in rheumatoid arthritis (RA) and golimumab in axial spondyloarthritis (axSpA), but with similar rates seen for most drugs used in the treatment of psoriasis and psoriatic arthritis (PsA), according to findings from a study of two Danish registries.

Drug survival refers to “the probability that patients will remain on a given drug, and is a proxy for efficacy as well as safety in daily clinical practice,” wrote Alexander Egeberg, MD, PhD, of the department of dermatology at Copenhagen University Hospital–Bispebjerg, and colleagues. Although the use of biologics has expanded for inflammatory diseases, real-world data on drug survival in newer agents such as interleukin (IL)-17, IL-23, and Janus kinase inhibitors are lacking, they said.

In a study published in Seminars in Arthritis and Rheumatism, the researchers reviewed data from the DANBIO and DERMBIO registries of patients in Denmark with inflammatory diseases including rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis.

The study population included 12,089 adults: 5,104 with RA, 2,157 with AxSpA, 2,251 with PsA, and 2,577 with psoriasis. Patients’ mean age at the time of first treatment for these conditions was 57.8 years, 42.3 years, 49 years, and 45 years, respectively. Participants were treated with biologics or novel small molecule therapies for RA, AxSpA, PsA, or psoriasis between January 2015 and May 2021 (from the DANBIO database) and November 2009 to November 2019 (DERMBIO database).

In adjusted models, drug survival in RA was highest for rituximab followed by baricitinib, etanercept, and tocilizumab. Drug survival in AxSpA was highest for golimumab, compared with all other drugs, followed by secukinumab and etanercept. Survival was lowest for infliximab. In PsA, drug survival was roughly equal for most drugs, including golimumab, secukinumab, and ixekizumab, with the lowest survival observed for tofacitinib and infliximab, compared with all other drugs. Drug survival in psoriasis was highest with guselkumab, followed by ustekinumab and IL-17 inhibitors.

However, the number of treatment series “was low for some drugs, and not all differences were statistically significant, which could influence the overall interpretability of these findings,” the researchers noted in their discussion.

Notably, the high treatment persistence for rituximab in RA patients needs further confirmation, the researchers said. “In Denmark, rituximab is often the biologic drug of choice in RA patients with a history of cancer while there is a reluctancy to use TNF [tumor necrosis factor] inhibitors in such patients; this may have prolonged the drug survival for rituximab treated patients due to limited treatment alternatives,” they said.

The findings were limited by several factors, including the observational study design and changes in guidelines over the course of the study, the researchers noted. Other limitations included the inability to adjust for certain variables, such as antibody status, body weight, and smoking, because of missing data, and a lack of data on the underlying reasons for drug discontinuation, they said.

However, the results were strengthened by the large number of patients and completeness of the registries, the researchers emphasized. The range in responses to different drug types across diseases supports the need for individualized treatments with attention to underlying disease, patient profile, and treatment history, they concluded.

The study received no outside funding. Eight coauthors reported financial ties to a number of pharmaceutical companies.

Survival rates of biologics and other novel immunomodulatory drugs vary substantially across chronic inflammatory diseases, and rates are highest for rituximab in rheumatoid arthritis (RA) and golimumab in axial spondyloarthritis (axSpA), but with similar rates seen for most drugs used in the treatment of psoriasis and psoriatic arthritis (PsA), according to findings from a study of two Danish registries.

Drug survival refers to “the probability that patients will remain on a given drug, and is a proxy for efficacy as well as safety in daily clinical practice,” wrote Alexander Egeberg, MD, PhD, of the department of dermatology at Copenhagen University Hospital–Bispebjerg, and colleagues. Although the use of biologics has expanded for inflammatory diseases, real-world data on drug survival in newer agents such as interleukin (IL)-17, IL-23, and Janus kinase inhibitors are lacking, they said.

In a study published in Seminars in Arthritis and Rheumatism, the researchers reviewed data from the DANBIO and DERMBIO registries of patients in Denmark with inflammatory diseases including rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis.

The study population included 12,089 adults: 5,104 with RA, 2,157 with AxSpA, 2,251 with PsA, and 2,577 with psoriasis. Patients’ mean age at the time of first treatment for these conditions was 57.8 years, 42.3 years, 49 years, and 45 years, respectively. Participants were treated with biologics or novel small molecule therapies for RA, AxSpA, PsA, or psoriasis between January 2015 and May 2021 (from the DANBIO database) and November 2009 to November 2019 (DERMBIO database).

In adjusted models, drug survival in RA was highest for rituximab followed by baricitinib, etanercept, and tocilizumab. Drug survival in AxSpA was highest for golimumab, compared with all other drugs, followed by secukinumab and etanercept. Survival was lowest for infliximab. In PsA, drug survival was roughly equal for most drugs, including golimumab, secukinumab, and ixekizumab, with the lowest survival observed for tofacitinib and infliximab, compared with all other drugs. Drug survival in psoriasis was highest with guselkumab, followed by ustekinumab and IL-17 inhibitors.

However, the number of treatment series “was low for some drugs, and not all differences were statistically significant, which could influence the overall interpretability of these findings,” the researchers noted in their discussion.

Notably, the high treatment persistence for rituximab in RA patients needs further confirmation, the researchers said. “In Denmark, rituximab is often the biologic drug of choice in RA patients with a history of cancer while there is a reluctancy to use TNF [tumor necrosis factor] inhibitors in such patients; this may have prolonged the drug survival for rituximab treated patients due to limited treatment alternatives,” they said.

The findings were limited by several factors, including the observational study design and changes in guidelines over the course of the study, the researchers noted. Other limitations included the inability to adjust for certain variables, such as antibody status, body weight, and smoking, because of missing data, and a lack of data on the underlying reasons for drug discontinuation, they said.

However, the results were strengthened by the large number of patients and completeness of the registries, the researchers emphasized. The range in responses to different drug types across diseases supports the need for individualized treatments with attention to underlying disease, patient profile, and treatment history, they concluded.

The study received no outside funding. Eight coauthors reported financial ties to a number of pharmaceutical companies.

Patients who have a rare subtype of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with isolated Hodgkin/Reed–Sternberg-like cells (CLL-HRS) may benefit from Hodgkin-directed therapy, based on data from 46 individuals.

Those patients who progress to classic Hodgkin lymphoma (CHL) from CLL/SLL are generally diagnosed based on straightforward pathology and treated with HRS cells in the same way as patients with de novo CHL, wrote lead author Dr. Rebecca L. King, a pathologist at the Mayo Clinic in Rochester, Minn.

However, in a small subset of patients, HRS cells occur in a background of CLL/SLL, in a condition known as CLL-HRS, and these patients do not progress to overt CHL, the researchers wrote.

Given the rarity of CLL-HRS, data on patient management are limited, they noted.

In a retrospective study published in Blood Cancer Journal, researchers reviewed outcome data from 15 adults with CLL-HRS and 31 adults with CLL/SLL who had overtly transformed to CLL-HL. The median age of the participants at the time of CLL-HL or CLL-HRS transformation diagnosis was 72 years; 71% and 87% of the CLL-HL and CLL-HRS patients, respectively, were male.

The median times from CLL to CLL-HL transformation and from CLL to CLL-HRS transformation were 6.6 years and 4.9 years, respectively; the difference was not statistically significant. The phenotypic features of Reed-Sternberg cells and Epstein-Barr virus status were similar in both patient groups. Two patients had biopsies in which both CLL-HRS and CLL-HL were present in the same tissue at initial diagnosis; they were included in the CLL-HL group for clinical analysis and in both groups for pathology analysis.

The median overall survival of CLL-HRS patients was 17.5 months, compared with 33.5 months for CLL-HL patients (P = .24), a nonsignificant difference. However, patients with CLL-HRS who received Hodgkin-directed therapy had a significantly longer median overall survival, compared with those who received CLL-directed therapy (57 months vs. 8.4 months, P = .02).

CLL-directed therapy included rituximab with or without corticosteroids, chemoimmunotherapy, or acalabrutinib; HL-directed therapy included doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine–based treatment; radiotherapy; or BCVPP (carmustine, cyclophosphamide, vinblastine, procarbazine, and prednisone).

Histopathology findings showed that CLL-HL patients had a background of mixed inflammation that was distinct from findings in CLL/SLL. CLL-HRS patients had a minimal inflammatory background, compared with CLL-HL cases, but researchers identified rosetting of T cells around the HRS cells in 56% of these patients.

“Our findings suggest that, clinically and pathologically, these patients show a spectrum of findings, and these two entities likely exist on a biologic continuum. Furthermore, our findings suggest that CLL-HRS patients managed with Hodgkin-directed therapy, rather than CLL-directed therapy, may have superior outcomes,” the researchers wrote.

The study findings were limited by several factors, including the retrospective design and the use of data from a single center. Therefore, the results should be validated in other cohorts, the researchers noted. In addition, the study participants were diagnosed over three decades, and management of the condition has significantly improved.

However, the results were strengthened by a review of data by three pathologists who were blinded to the clinical outcomes, they said.

“These findings have important implications for a scenario in which clinical guidelines are lacking and suggest that hematologists treating patients with CLL-HRS should consider HL-directed therapy,” the researchers concluded.

In an interview, Jennifer A. Woyach, MD, a hematologist at Ohio State University, Columbus, commented on the study findings: “Hodgkin transformation and CLL with Hodgkin-like cells likely represent a biologic continuum, and care should be taken to obtain adequate biopsies, so that the diagnosis of Hodgkin transformation can be made when appropriate.”

“Interestingly, the authors noted a trend toward improved survival when CLL with Hodgkin-like cells was treated with standard Hodgkin regimens,” said Dr. Woyach. “With the small patient numbers, this certainly cannot be a general recommendation, but should be considered by treating physicians on a case-by-case basis.”

“While we know that patients with Hodgkin transformation can in many cases be successfully treated with standard Hodgkin regimen, the natural history and optimal treatment for CLL with Hodgkin-like cells have been unknown. This analysis helps understand the biologic difference between these two clinicopathologic entities to understand how to better treat patients,” she noted. Going forward, “it would be extremely helpful to see these data validated by other centers to be sure that these results are reproducible,” Dr. Woyach added.

The study was supported by the Mayo Clinic, Rochester, Minn., and by the Henry J. Predolin Foundation. Lead author Dr. King disclosed research support to her institution from Bristol-Myers Squibb/Celgene. Dr. Woyach had no financial disclosures relevant to this study, but she has received laboratory research funding from Schrodinger and has consulted for AbbVie, Pharmacyclics, Janssen, AstraZeneca, Genentech, Beigene, Loxo, and Newave.
 

This article was updated 3/11/22.

Patients who have a rare subtype of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with isolated Hodgkin/Reed–Sternberg-like cells (CLL-HRS) may benefit from Hodgkin-directed therapy, based on data from 46 individuals.

Those patients who progress to classic Hodgkin lymphoma (CHL) from CLL/SLL are generally diagnosed based on straightforward pathology and treated with HRS cells in the same way as patients with de novo CHL, wrote lead author Dr. Rebecca L. King, a pathologist at the Mayo Clinic in Rochester, Minn.

However, in a small subset of patients, HRS cells occur in a background of CLL/SLL, in a condition known as CLL-HRS, and these patients do not progress to overt CHL, the researchers wrote.

Given the rarity of CLL-HRS, data on patient management are limited, they noted.

In a retrospective study published in Blood Cancer Journal, researchers reviewed outcome data from 15 adults with CLL-HRS and 31 adults with CLL/SLL who had overtly transformed to CLL-HL. The median age of the participants at the time of CLL-HL or CLL-HRS transformation diagnosis was 72 years; 71% and 87% of the CLL-HL and CLL-HRS patients, respectively, were male.

The median times from CLL to CLL-HL transformation and from CLL to CLL-HRS transformation were 6.6 years and 4.9 years, respectively; the difference was not statistically significant. The phenotypic features of Reed-Sternberg cells and Epstein-Barr virus status were similar in both patient groups. Two patients had biopsies in which both CLL-HRS and CLL-HL were present in the same tissue at initial diagnosis; they were included in the CLL-HL group for clinical analysis and in both groups for pathology analysis.

The median overall survival of CLL-HRS patients was 17.5 months, compared with 33.5 months for CLL-HL patients (P = .24), a nonsignificant difference. However, patients with CLL-HRS who received Hodgkin-directed therapy had a significantly longer median overall survival, compared with those who received CLL-directed therapy (57 months vs. 8.4 months, P = .02).

CLL-directed therapy included rituximab with or without corticosteroids, chemoimmunotherapy, or acalabrutinib; HL-directed therapy included doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine–based treatment; radiotherapy; or BCVPP (carmustine, cyclophosphamide, vinblastine, procarbazine, and prednisone).

Histopathology findings showed that CLL-HL patients had a background of mixed inflammation that was distinct from findings in CLL/SLL. CLL-HRS patients had a minimal inflammatory background, compared with CLL-HL cases, but researchers identified rosetting of T cells around the HRS cells in 56% of these patients.

“Our findings suggest that, clinically and pathologically, these patients show a spectrum of findings, and these two entities likely exist on a biologic continuum. Furthermore, our findings suggest that CLL-HRS patients managed with Hodgkin-directed therapy, rather than CLL-directed therapy, may have superior outcomes,” the researchers wrote.

The study findings were limited by several factors, including the retrospective design and the use of data from a single center. Therefore, the results should be validated in other cohorts, the researchers noted. In addition, the study participants were diagnosed over three decades, and management of the condition has significantly improved.

However, the results were strengthened by a review of data by three pathologists who were blinded to the clinical outcomes, they said.

“These findings have important implications for a scenario in which clinical guidelines are lacking and suggest that hematologists treating patients with CLL-HRS should consider HL-directed therapy,” the researchers concluded.

In an interview, Jennifer A. Woyach, MD, a hematologist at Ohio State University, Columbus, commented on the study findings: “Hodgkin transformation and CLL with Hodgkin-like cells likely represent a biologic continuum, and care should be taken to obtain adequate biopsies, so that the diagnosis of Hodgkin transformation can be made when appropriate.”

“Interestingly, the authors noted a trend toward improved survival when CLL with Hodgkin-like cells was treated with standard Hodgkin regimens,” said Dr. Woyach. “With the small patient numbers, this certainly cannot be a general recommendation, but should be considered by treating physicians on a case-by-case basis.”

“While we know that patients with Hodgkin transformation can in many cases be successfully treated with standard Hodgkin regimen, the natural history and optimal treatment for CLL with Hodgkin-like cells have been unknown. This analysis helps understand the biologic difference between these two clinicopathologic entities to understand how to better treat patients,” she noted. Going forward, “it would be extremely helpful to see these data validated by other centers to be sure that these results are reproducible,” Dr. Woyach added.

The study was supported by the Mayo Clinic, Rochester, Minn., and by the Henry J. Predolin Foundation. Lead author Dr. King disclosed research support to her institution from Bristol-Myers Squibb/Celgene. Dr. Woyach had no financial disclosures relevant to this study, but she has received laboratory research funding from Schrodinger and has consulted for AbbVie, Pharmacyclics, Janssen, AstraZeneca, Genentech, Beigene, Loxo, and Newave.
 

This article was updated 3/11/22.

Patients who have a rare subtype of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with isolated Hodgkin/Reed–Sternberg-like cells (CLL-HRS) may benefit from Hodgkin-directed therapy, based on data from 46 individuals.

Those patients who progress to classic Hodgkin lymphoma (CHL) from CLL/SLL are generally diagnosed based on straightforward pathology and treated with HRS cells in the same way as patients with de novo CHL, wrote lead author Dr. Rebecca L. King, a pathologist at the Mayo Clinic in Rochester, Minn.

However, in a small subset of patients, HRS cells occur in a background of CLL/SLL, in a condition known as CLL-HRS, and these patients do not progress to overt CHL, the researchers wrote.

Given the rarity of CLL-HRS, data on patient management are limited, they noted.

In a retrospective study published in Blood Cancer Journal, researchers reviewed outcome data from 15 adults with CLL-HRS and 31 adults with CLL/SLL who had overtly transformed to CLL-HL. The median age of the participants at the time of CLL-HL or CLL-HRS transformation diagnosis was 72 years; 71% and 87% of the CLL-HL and CLL-HRS patients, respectively, were male.

The median times from CLL to CLL-HL transformation and from CLL to CLL-HRS transformation were 6.6 years and 4.9 years, respectively; the difference was not statistically significant. The phenotypic features of Reed-Sternberg cells and Epstein-Barr virus status were similar in both patient groups. Two patients had biopsies in which both CLL-HRS and CLL-HL were present in the same tissue at initial diagnosis; they were included in the CLL-HL group for clinical analysis and in both groups for pathology analysis.

The median overall survival of CLL-HRS patients was 17.5 months, compared with 33.5 months for CLL-HL patients (P = .24), a nonsignificant difference. However, patients with CLL-HRS who received Hodgkin-directed therapy had a significantly longer median overall survival, compared with those who received CLL-directed therapy (57 months vs. 8.4 months, P = .02).

CLL-directed therapy included rituximab with or without corticosteroids, chemoimmunotherapy, or acalabrutinib; HL-directed therapy included doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine–based treatment; radiotherapy; or BCVPP (carmustine, cyclophosphamide, vinblastine, procarbazine, and prednisone).

Histopathology findings showed that CLL-HL patients had a background of mixed inflammation that was distinct from findings in CLL/SLL. CLL-HRS patients had a minimal inflammatory background, compared with CLL-HL cases, but researchers identified rosetting of T cells around the HRS cells in 56% of these patients.

“Our findings suggest that, clinically and pathologically, these patients show a spectrum of findings, and these two entities likely exist on a biologic continuum. Furthermore, our findings suggest that CLL-HRS patients managed with Hodgkin-directed therapy, rather than CLL-directed therapy, may have superior outcomes,” the researchers wrote.

The study findings were limited by several factors, including the retrospective design and the use of data from a single center. Therefore, the results should be validated in other cohorts, the researchers noted. In addition, the study participants were diagnosed over three decades, and management of the condition has significantly improved.

However, the results were strengthened by a review of data by three pathologists who were blinded to the clinical outcomes, they said.

“These findings have important implications for a scenario in which clinical guidelines are lacking and suggest that hematologists treating patients with CLL-HRS should consider HL-directed therapy,” the researchers concluded.

In an interview, Jennifer A. Woyach, MD, a hematologist at Ohio State University, Columbus, commented on the study findings: “Hodgkin transformation and CLL with Hodgkin-like cells likely represent a biologic continuum, and care should be taken to obtain adequate biopsies, so that the diagnosis of Hodgkin transformation can be made when appropriate.”

“Interestingly, the authors noted a trend toward improved survival when CLL with Hodgkin-like cells was treated with standard Hodgkin regimens,” said Dr. Woyach. “With the small patient numbers, this certainly cannot be a general recommendation, but should be considered by treating physicians on a case-by-case basis.”

“While we know that patients with Hodgkin transformation can in many cases be successfully treated with standard Hodgkin regimen, the natural history and optimal treatment for CLL with Hodgkin-like cells have been unknown. This analysis helps understand the biologic difference between these two clinicopathologic entities to understand how to better treat patients,” she noted. Going forward, “it would be extremely helpful to see these data validated by other centers to be sure that these results are reproducible,” Dr. Woyach added.

The study was supported by the Mayo Clinic, Rochester, Minn., and by the Henry J. Predolin Foundation. Lead author Dr. King disclosed research support to her institution from Bristol-Myers Squibb/Celgene. Dr. Woyach had no financial disclosures relevant to this study, but she has received laboratory research funding from Schrodinger and has consulted for AbbVie, Pharmacyclics, Janssen, AstraZeneca, Genentech, Beigene, Loxo, and Newave.
 

This article was updated 3/11/22.

Pseudomonas aeruginosa persisted in the airways of patients with chronic obstructive pulmonary disease (COPD), based on data from 23 patients over a 1-year period.

P. aeruginosa is cultured in as many as 20% of bacterial exacerbations and has been linked to increased morbidity and mortality in patients with COPD, wrote Josefin Eklöf, MD, of the University of Copenhagen and colleagues. However, its patterns and characteristics have not been well studied, and researchers proposed that P. aerunginosa persists in COPD patients in part because of genetic adaptations in the genes related to antibiotic resistance.

In a study published in Clinical Microbiology and Infection, the researchers identified 23 consecutive patients enrolled in an ongoing randomized clinical trial at four sites in Denmark between Jan. 2018 and Jan. 2020. Participants were randomized 1:1 to targeted antipseudomonal antibiotic treatment for 14 days (between visit day 1 and visit day 14) or no antipseudomonal treatment. Sputum samples were collected at baseline on day 1 and on days 14, 30, 60, 90, and 365.

The researchers sequenced isolates from 23 adult patients over 365 days of follow-up. The recurrence of P. aeruginosa occurred in 19 patients (83%) during this period. Ultimately, a total of 153 isolates were analyzed. The researchers found that each patient carried their own unique lineage, with the except of one patient in whom two distinct lineages were identified.

“Independent mutation of the same gene across multiple lineages may be the result of positive selection of adaptive mutations,” Dr. Eklöf and colleagues wrote. They found 38 genes for P. aeruginosa that were mutated in at least two lineages, which suggested adaptive mutations. Some of the more frequently mutated genes were those important to antibiotic resistance and chronic infections, the researchers said. Specifically, mutations occurred in 40 of 140 pathoadaptive genes, compared with 265 of 5,572 other genes (P < .001). In addition, the 24 total lineages carried 4-6 antibiotic resistance genes, and no evidence suggested that lineages acquired or lost these genes during carriage.

Overall, the results indicate that the recurrence of P. aeruginosa was caused by persistence of the same clonal lineage in each patient. “This pattern of persistence was associated with genetic adaptation related to phenotypes considered important for P. aeruginosa infections,” the researchers said.

The study findings were limited by the relatively small number of samples and isolates per sample, the follow-up of only 1 year, and the inability to account for mutations in the early stage because few patients were naive to P. aeruginosa at the start of the study, the researchers noted. However, the results were strengthened by the relatively large and well-defined study population and high rate of sampling compliance, they said.

Overall, “the findings warrant research to improve therapy, including trial data on possible clinical benefits of attempting antibiotic eradication of P. aeruginosa in this vulnerable group of patients,” they concluded.

The study was supported by the Independent Research Fund Denmark and the Research committee at Copenhagen University Hospital-Herlev and Gentofte Hospital. The researchers had no financial conflicts to disclose.

Pseudomonas aeruginosa persisted in the airways of patients with chronic obstructive pulmonary disease (COPD), based on data from 23 patients over a 1-year period.

P. aeruginosa is cultured in as many as 20% of bacterial exacerbations and has been linked to increased morbidity and mortality in patients with COPD, wrote Josefin Eklöf, MD, of the University of Copenhagen and colleagues. However, its patterns and characteristics have not been well studied, and researchers proposed that P. aerunginosa persists in COPD patients in part because of genetic adaptations in the genes related to antibiotic resistance.

In a study published in Clinical Microbiology and Infection, the researchers identified 23 consecutive patients enrolled in an ongoing randomized clinical trial at four sites in Denmark between Jan. 2018 and Jan. 2020. Participants were randomized 1:1 to targeted antipseudomonal antibiotic treatment for 14 days (between visit day 1 and visit day 14) or no antipseudomonal treatment. Sputum samples were collected at baseline on day 1 and on days 14, 30, 60, 90, and 365.

The researchers sequenced isolates from 23 adult patients over 365 days of follow-up. The recurrence of P. aeruginosa occurred in 19 patients (83%) during this period. Ultimately, a total of 153 isolates were analyzed. The researchers found that each patient carried their own unique lineage, with the except of one patient in whom two distinct lineages were identified.

“Independent mutation of the same gene across multiple lineages may be the result of positive selection of adaptive mutations,” Dr. Eklöf and colleagues wrote. They found 38 genes for P. aeruginosa that were mutated in at least two lineages, which suggested adaptive mutations. Some of the more frequently mutated genes were those important to antibiotic resistance and chronic infections, the researchers said. Specifically, mutations occurred in 40 of 140 pathoadaptive genes, compared with 265 of 5,572 other genes (P < .001). In addition, the 24 total lineages carried 4-6 antibiotic resistance genes, and no evidence suggested that lineages acquired or lost these genes during carriage.

Overall, the results indicate that the recurrence of P. aeruginosa was caused by persistence of the same clonal lineage in each patient. “This pattern of persistence was associated with genetic adaptation related to phenotypes considered important for P. aeruginosa infections,” the researchers said.

The study findings were limited by the relatively small number of samples and isolates per sample, the follow-up of only 1 year, and the inability to account for mutations in the early stage because few patients were naive to P. aeruginosa at the start of the study, the researchers noted. However, the results were strengthened by the relatively large and well-defined study population and high rate of sampling compliance, they said.

Overall, “the findings warrant research to improve therapy, including trial data on possible clinical benefits of attempting antibiotic eradication of P. aeruginosa in this vulnerable group of patients,” they concluded.

The study was supported by the Independent Research Fund Denmark and the Research committee at Copenhagen University Hospital-Herlev and Gentofte Hospital. The researchers had no financial conflicts to disclose.

Pseudomonas aeruginosa persisted in the airways of patients with chronic obstructive pulmonary disease (COPD), based on data from 23 patients over a 1-year period.

P. aeruginosa is cultured in as many as 20% of bacterial exacerbations and has been linked to increased morbidity and mortality in patients with COPD, wrote Josefin Eklöf, MD, of the University of Copenhagen and colleagues. However, its patterns and characteristics have not been well studied, and researchers proposed that P. aerunginosa persists in COPD patients in part because of genetic adaptations in the genes related to antibiotic resistance.

In a study published in Clinical Microbiology and Infection, the researchers identified 23 consecutive patients enrolled in an ongoing randomized clinical trial at four sites in Denmark between Jan. 2018 and Jan. 2020. Participants were randomized 1:1 to targeted antipseudomonal antibiotic treatment for 14 days (between visit day 1 and visit day 14) or no antipseudomonal treatment. Sputum samples were collected at baseline on day 1 and on days 14, 30, 60, 90, and 365.

The researchers sequenced isolates from 23 adult patients over 365 days of follow-up. The recurrence of P. aeruginosa occurred in 19 patients (83%) during this period. Ultimately, a total of 153 isolates were analyzed. The researchers found that each patient carried their own unique lineage, with the except of one patient in whom two distinct lineages were identified.

“Independent mutation of the same gene across multiple lineages may be the result of positive selection of adaptive mutations,” Dr. Eklöf and colleagues wrote. They found 38 genes for P. aeruginosa that were mutated in at least two lineages, which suggested adaptive mutations. Some of the more frequently mutated genes were those important to antibiotic resistance and chronic infections, the researchers said. Specifically, mutations occurred in 40 of 140 pathoadaptive genes, compared with 265 of 5,572 other genes (P < .001). In addition, the 24 total lineages carried 4-6 antibiotic resistance genes, and no evidence suggested that lineages acquired or lost these genes during carriage.

Overall, the results indicate that the recurrence of P. aeruginosa was caused by persistence of the same clonal lineage in each patient. “This pattern of persistence was associated with genetic adaptation related to phenotypes considered important for P. aeruginosa infections,” the researchers said.

The study findings were limited by the relatively small number of samples and isolates per sample, the follow-up of only 1 year, and the inability to account for mutations in the early stage because few patients were naive to P. aeruginosa at the start of the study, the researchers noted. However, the results were strengthened by the relatively large and well-defined study population and high rate of sampling compliance, they said.

Overall, “the findings warrant research to improve therapy, including trial data on possible clinical benefits of attempting antibiotic eradication of P. aeruginosa in this vulnerable group of patients,” they concluded.

The study was supported by the Independent Research Fund Denmark and the Research committee at Copenhagen University Hospital-Herlev and Gentofte Hospital. The researchers had no financial conflicts to disclose.

Heavier smoking significantly increased mortality in adults with progressive fibrosing interstitial lung disease (PF-ILD), based on data from 377 individuals.

The negative impact of smoking on pulmonary diseases is well documented, but the specific impact on patients with PF-ILD has not been well studied, Mark Platenburg, MD, of St. Antonious Hospital, Nieuwegein, the Netherlands, and colleagues wrote in Respiratory Medicine .

GaryPhoto/ThinkStock

“Patients with PF-ILD or IPF [idiopathic pulmonary fibrosis] are prone to early mortality, indicating a need for prognostic [bio]marker studies for precision medicine,” they said.

The researchers identified adults older than 18 years with PF-ILD who were diagnosed at a single center. All study participants had at least 10% fibrosis, and showed either a decline of at least 10% in forced vital capacity, a 5.0%-9.9% relative FVC decline plus progressive respiratory symptoms and/or an increase in extent of fibrosis on subsequent high-resolution (HRCT progression), or progressive respiratory symptoms and HRCT progression over 24 months after ILD diagnosis.

Pack-years of smoking was a prognostic variable; the researchers also compared median transplant-free survival in heavy smokers and mild to moderate smokers. They also investigated the association between smoking quantity and emphysema in the study population.

Overall, the increased risk for mortality was 11%, 22%, and 44% in patients with 10, 20, and 40 pack-years of smoking, respectively.

Both the unadjusted and adjusted hazard ratio for pack-years were significant (1.014, P < .001 and 1.011, P = .022, respectively).

The median transplant-free survival of ever-smokers versus never-smokers with PF-ILD was 3.3 years versus 4.8 years; median transplant-free survival was 3.0 years for heavy smokers and 3.8 years for mild to moderate smokers. Similarly, median survival was 4.2 years in never-smokers versus 3.0 years in former smokers.

Emphysema was significantly more comment in heavy smokers, compared with never smokers and mild to moderate smokers (P < .001 for both).

“We observed a gradual decrease in survival starting from never to mild-moderate and subsequent heavy smokers supporting our finding that [pack-years] is an independent predictor for mortality in PF-ILD,” the researchers wrote. “This is an important message that clinicians could convey to their ILD patients, but also to patients at-risk for ILD.”

The study findings were limited by several factors, mainly the retrospective design, incomplete data for some patients, and lack of data on comorbidities, the researchers noted. However, the results strengthen the evidence for the detrimental effect of heavy smoking in PF-ILD, they said. Consequently, “efforts to reduce pack-years in those with, and at risk for, PF-ILD may translate into a survival benefit and should have high priority in clinical practice.”

The study was supported by grants from ZonMw TopZorg Care and TZO. The researchers had no financial conflicts to disclose.

Heavier smoking significantly increased mortality in adults with progressive fibrosing interstitial lung disease (PF-ILD), based on data from 377 individuals.

The negative impact of smoking on pulmonary diseases is well documented, but the specific impact on patients with PF-ILD has not been well studied, Mark Platenburg, MD, of St. Antonious Hospital, Nieuwegein, the Netherlands, and colleagues wrote in Respiratory Medicine .

GaryPhoto/ThinkStock

“Patients with PF-ILD or IPF [idiopathic pulmonary fibrosis] are prone to early mortality, indicating a need for prognostic [bio]marker studies for precision medicine,” they said.

The researchers identified adults older than 18 years with PF-ILD who were diagnosed at a single center. All study participants had at least 10% fibrosis, and showed either a decline of at least 10% in forced vital capacity, a 5.0%-9.9% relative FVC decline plus progressive respiratory symptoms and/or an increase in extent of fibrosis on subsequent high-resolution (HRCT progression), or progressive respiratory symptoms and HRCT progression over 24 months after ILD diagnosis.

Pack-years of smoking was a prognostic variable; the researchers also compared median transplant-free survival in heavy smokers and mild to moderate smokers. They also investigated the association between smoking quantity and emphysema in the study population.

Overall, the increased risk for mortality was 11%, 22%, and 44% in patients with 10, 20, and 40 pack-years of smoking, respectively.

Both the unadjusted and adjusted hazard ratio for pack-years were significant (1.014, P < .001 and 1.011, P = .022, respectively).

The median transplant-free survival of ever-smokers versus never-smokers with PF-ILD was 3.3 years versus 4.8 years; median transplant-free survival was 3.0 years for heavy smokers and 3.8 years for mild to moderate smokers. Similarly, median survival was 4.2 years in never-smokers versus 3.0 years in former smokers.

Emphysema was significantly more comment in heavy smokers, compared with never smokers and mild to moderate smokers (P < .001 for both).

“We observed a gradual decrease in survival starting from never to mild-moderate and subsequent heavy smokers supporting our finding that [pack-years] is an independent predictor for mortality in PF-ILD,” the researchers wrote. “This is an important message that clinicians could convey to their ILD patients, but also to patients at-risk for ILD.”

The study findings were limited by several factors, mainly the retrospective design, incomplete data for some patients, and lack of data on comorbidities, the researchers noted. However, the results strengthen the evidence for the detrimental effect of heavy smoking in PF-ILD, they said. Consequently, “efforts to reduce pack-years in those with, and at risk for, PF-ILD may translate into a survival benefit and should have high priority in clinical practice.”

The study was supported by grants from ZonMw TopZorg Care and TZO. The researchers had no financial conflicts to disclose.

Heavier smoking significantly increased mortality in adults with progressive fibrosing interstitial lung disease (PF-ILD), based on data from 377 individuals.

The negative impact of smoking on pulmonary diseases is well documented, but the specific impact on patients with PF-ILD has not been well studied, Mark Platenburg, MD, of St. Antonious Hospital, Nieuwegein, the Netherlands, and colleagues wrote in Respiratory Medicine .

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“Patients with PF-ILD or IPF [idiopathic pulmonary fibrosis] are prone to early mortality, indicating a need for prognostic [bio]marker studies for precision medicine,” they said.

The researchers identified adults older than 18 years with PF-ILD who were diagnosed at a single center. All study participants had at least 10% fibrosis, and showed either a decline of at least 10% in forced vital capacity, a 5.0%-9.9% relative FVC decline plus progressive respiratory symptoms and/or an increase in extent of fibrosis on subsequent high-resolution (HRCT progression), or progressive respiratory symptoms and HRCT progression over 24 months after ILD diagnosis.

Pack-years of smoking was a prognostic variable; the researchers also compared median transplant-free survival in heavy smokers and mild to moderate smokers. They also investigated the association between smoking quantity and emphysema in the study population.

Overall, the increased risk for mortality was 11%, 22%, and 44% in patients with 10, 20, and 40 pack-years of smoking, respectively.

Both the unadjusted and adjusted hazard ratio for pack-years were significant (1.014, P < .001 and 1.011, P = .022, respectively).

The median transplant-free survival of ever-smokers versus never-smokers with PF-ILD was 3.3 years versus 4.8 years; median transplant-free survival was 3.0 years for heavy smokers and 3.8 years for mild to moderate smokers. Similarly, median survival was 4.2 years in never-smokers versus 3.0 years in former smokers.

Emphysema was significantly more comment in heavy smokers, compared with never smokers and mild to moderate smokers (P < .001 for both).

“We observed a gradual decrease in survival starting from never to mild-moderate and subsequent heavy smokers supporting our finding that [pack-years] is an independent predictor for mortality in PF-ILD,” the researchers wrote. “This is an important message that clinicians could convey to their ILD patients, but also to patients at-risk for ILD.”

The study findings were limited by several factors, mainly the retrospective design, incomplete data for some patients, and lack of data on comorbidities, the researchers noted. However, the results strengthen the evidence for the detrimental effect of heavy smoking in PF-ILD, they said. Consequently, “efforts to reduce pack-years in those with, and at risk for, PF-ILD may translate into a survival benefit and should have high priority in clinical practice.”

The study was supported by grants from ZonMw TopZorg Care and TZO. The researchers had no financial conflicts to disclose.