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How the microbiome influences the success of cancer therapy
HAMBURG, Germany — The human microbiome comprises 39 to 44 billion microbes. That is ten times more than the number of cells in our body. Hendrik Poeck, MD, managing senior physician of internal medicine at the University Hospital Regensburg, illustrated this point at the annual meeting of the German Society for Hematology and Medical Oncology. If the gut microbiome falls out of balance, then “intestinal dysbiosis potentially poses a risk for the pathogenesis of local and systemic diseases,” explained Dr. Poeck.
Cancers and their therapies can also be influenced in this way. said Dr. Poeck.
Microbial diversity could be beneficial for cancer therapy, too. The composition of the microbiome varies significantly from host to host and can mutate. These properties make it a target for precision microbiotics, which involves using the gut microbiome as a biomarker to predict various physical reactions and to develop individualized diets.
Microbiome and Pathogenesis
The body’s microbiome fulfills a barrier function, especially where the body is exposed to an external environment: at the epidermis and the internal mucous membranes, in the gastrointestinal tract, and in the lungs, chest, and urogenital system.
Association studies on humans and experimental manipulations on mouse models of cancer showed that certain microorganisms can have either protective or harmful effects on cancer development, on the progression of a malignant disease, and on the response to therapy.
A Master Regulator?
Disruptions of the microbial system in the gut, as occur during antibiotic therapy, can have significant effects on a patient’s response to immunotherapy. Taking antibiotics shortly before or after starting therapy with immune checkpoint inhibitors (ICIs) significantly affected both overall survival (OS) and progression-free survival (PFS), as reported in a recent review and meta-analysis, for example.
Proton pump inhibitors also affect the gut microbiome and reduce the response to immunotherapy; this effect was demonstrated by an analysis of data from more than 2700 cancer patients that was recently presented at the annual meeting of the European Society for Medical Oncology (ESMO).
The extent to which the gut microbiome influences the efficacy of an ICI or predicts said efficacy was examined in a retrospective analysis published in Science in 2018, which Dr. Poeck presented. Resistance to ICI correlated with the relative frequency of the bacteria Akkermansia muciniphila in the gut of patients with cancer. In mouse models, the researchers restored the efficacy of the PD-1 blockade through a stool transplant.
Predicting Immunotherapy Response
If A muciniphila is present, can the composition of the microbiome act as a predictor for an effective ICI therapy?
Laurence Zitvogel, MD, PhD, and her working group at the National Institute of Health and Medical Research in Villejuif, France, performed a prospective study in 338 patients with non–small cell lung cancer and examined the prognostic significance of the fecal bacteria A muciniphila (Akk). The “Akkerman status” (low Akk vs high Akk) in a patient’s stool correlated with an increased objective response rate and a longer OS, independently of PD-L1 expression, antibiotics, and performance status. The OS for low Akk was 13.4 months, vs 18.8 months for high Akk in first-line treatment.
These results are promising, said Dr. Poeck. But there is no one-size-fits-all solution. No conclusions can be drawn from one bacterium on the efficacy of therapies in humans, since “the entirety of the bacteria is decisive,” said Dr. Poeck. In addition to the gut microbiome, the composition of gut metabolites influences the response to immunotherapies, as shown in a study with ICI.
Therapeutic Interventions
One possible therapeutic intervention to restore the gut microbiome is fecal microbiota transplantation (FMT). In a phase 1 study presented by Dr. Poeck, FMT was effective in the treatment of 20 patients with melanoma with ICI in an advanced and treatment-naive stage. Seven days after the patients received FMT, the first cycle with anti-PD-1 immunotherapy was initiated, with a total administration of three to four cycles. After 12 weeks, most patients were in complete or partial remission, as evidenced on imaging.
However, FMT also carries some risks. Two cases of sepsis with multiresistant Escherichia coli occurred, as well as other serious infections. Since then, there has been an FDA condition for extended screening of the donor stool, said Dr. Poeck. Nevertheless, this intervention is promising. A search of the keywords “FMT in cancer/transplant setting” reveals 46 currently clinical studies on clinicaltrials.gov.
Nutritional Interventions
Dr. Poeck advises caution about over-the-counter products. These products usually contain only a few species, such as Lactobacillus and Bifidobacterium. “Over-the-counter probiotics can even delay the reconstitution of the microbiome after antibiotics,” said Dr. Poeck, according to a study. In some studies, the response rates were significantly lower after probiotic intake or led to controversial results, according to Dr. Poeck.
In contrast, Dr. Poeck said prebiotics (that is, a fiber-rich diet with indigestible carbohydrates) were promising. During digestion, prebiotics are split into short-chain fatty acids by bacterial enzymes and promote the growth of certain microbiota.
In this way, just 20 g of extremely fiber-rich food had a significant effect on PFS in 128 patients with melanoma undergoing anti-PD-1 immunotherapy. With 20 g of fiber-rich food per day, the PFS was stable over 60 months. The most significant benefit was observed in patients with a sufficient fiber intake who were not taking probiotics.
What to Recommend?
In summary, Dr. Poeck said that it is important to “budget” well, particularly with antibiotic administration, and to strive for calculated therapy with as narrow a spectrum as possible. For patients who experience complications such as cytokine release syndrome as a reaction to cell therapy, delaying the use of antibiotics is important. However, it is often difficult to differentiate this syndrome from neutropenic fever. The aim should be to avoid high-risk antibiotics, if clinically justifiable. Patients should avoid taking antibiotics for 30 days before starting immunotherapy.
Regarding nutritional interventions, Dr. Poeck referred to the recent Onkopedia recommendation for nutrition after cancer and the 10 nutritional rules of the German Nutrition Society. According to Dr. Poeck, the important aspects of these recommendations are a fiber-rich diet (> 20 g/d) from various plant products and avoiding artificial sweeteners and flavorings, as well as ultraprocessed (convenience) foods. In addition, meat should be consumed only in moderation, and as little processed meat as possible should be consumed. In addition, regular (aerobic and anaerobic) physical activity is important.
“Looking ahead into the future,” said Dr. Poeck, “we need a uniform and functional understanding and we need a randomized prediction for diagnosis.”
This article was translated from the Medscape German edition.
A version of this article appeared on Medscape.com.
HAMBURG, Germany — The human microbiome comprises 39 to 44 billion microbes. That is ten times more than the number of cells in our body. Hendrik Poeck, MD, managing senior physician of internal medicine at the University Hospital Regensburg, illustrated this point at the annual meeting of the German Society for Hematology and Medical Oncology. If the gut microbiome falls out of balance, then “intestinal dysbiosis potentially poses a risk for the pathogenesis of local and systemic diseases,” explained Dr. Poeck.
Cancers and their therapies can also be influenced in this way. said Dr. Poeck.
Microbial diversity could be beneficial for cancer therapy, too. The composition of the microbiome varies significantly from host to host and can mutate. These properties make it a target for precision microbiotics, which involves using the gut microbiome as a biomarker to predict various physical reactions and to develop individualized diets.
Microbiome and Pathogenesis
The body’s microbiome fulfills a barrier function, especially where the body is exposed to an external environment: at the epidermis and the internal mucous membranes, in the gastrointestinal tract, and in the lungs, chest, and urogenital system.
Association studies on humans and experimental manipulations on mouse models of cancer showed that certain microorganisms can have either protective or harmful effects on cancer development, on the progression of a malignant disease, and on the response to therapy.
A Master Regulator?
Disruptions of the microbial system in the gut, as occur during antibiotic therapy, can have significant effects on a patient’s response to immunotherapy. Taking antibiotics shortly before or after starting therapy with immune checkpoint inhibitors (ICIs) significantly affected both overall survival (OS) and progression-free survival (PFS), as reported in a recent review and meta-analysis, for example.
Proton pump inhibitors also affect the gut microbiome and reduce the response to immunotherapy; this effect was demonstrated by an analysis of data from more than 2700 cancer patients that was recently presented at the annual meeting of the European Society for Medical Oncology (ESMO).
The extent to which the gut microbiome influences the efficacy of an ICI or predicts said efficacy was examined in a retrospective analysis published in Science in 2018, which Dr. Poeck presented. Resistance to ICI correlated with the relative frequency of the bacteria Akkermansia muciniphila in the gut of patients with cancer. In mouse models, the researchers restored the efficacy of the PD-1 blockade through a stool transplant.
Predicting Immunotherapy Response
If A muciniphila is present, can the composition of the microbiome act as a predictor for an effective ICI therapy?
Laurence Zitvogel, MD, PhD, and her working group at the National Institute of Health and Medical Research in Villejuif, France, performed a prospective study in 338 patients with non–small cell lung cancer and examined the prognostic significance of the fecal bacteria A muciniphila (Akk). The “Akkerman status” (low Akk vs high Akk) in a patient’s stool correlated with an increased objective response rate and a longer OS, independently of PD-L1 expression, antibiotics, and performance status. The OS for low Akk was 13.4 months, vs 18.8 months for high Akk in first-line treatment.
These results are promising, said Dr. Poeck. But there is no one-size-fits-all solution. No conclusions can be drawn from one bacterium on the efficacy of therapies in humans, since “the entirety of the bacteria is decisive,” said Dr. Poeck. In addition to the gut microbiome, the composition of gut metabolites influences the response to immunotherapies, as shown in a study with ICI.
Therapeutic Interventions
One possible therapeutic intervention to restore the gut microbiome is fecal microbiota transplantation (FMT). In a phase 1 study presented by Dr. Poeck, FMT was effective in the treatment of 20 patients with melanoma with ICI in an advanced and treatment-naive stage. Seven days after the patients received FMT, the first cycle with anti-PD-1 immunotherapy was initiated, with a total administration of three to four cycles. After 12 weeks, most patients were in complete or partial remission, as evidenced on imaging.
However, FMT also carries some risks. Two cases of sepsis with multiresistant Escherichia coli occurred, as well as other serious infections. Since then, there has been an FDA condition for extended screening of the donor stool, said Dr. Poeck. Nevertheless, this intervention is promising. A search of the keywords “FMT in cancer/transplant setting” reveals 46 currently clinical studies on clinicaltrials.gov.
Nutritional Interventions
Dr. Poeck advises caution about over-the-counter products. These products usually contain only a few species, such as Lactobacillus and Bifidobacterium. “Over-the-counter probiotics can even delay the reconstitution of the microbiome after antibiotics,” said Dr. Poeck, according to a study. In some studies, the response rates were significantly lower after probiotic intake or led to controversial results, according to Dr. Poeck.
In contrast, Dr. Poeck said prebiotics (that is, a fiber-rich diet with indigestible carbohydrates) were promising. During digestion, prebiotics are split into short-chain fatty acids by bacterial enzymes and promote the growth of certain microbiota.
In this way, just 20 g of extremely fiber-rich food had a significant effect on PFS in 128 patients with melanoma undergoing anti-PD-1 immunotherapy. With 20 g of fiber-rich food per day, the PFS was stable over 60 months. The most significant benefit was observed in patients with a sufficient fiber intake who were not taking probiotics.
What to Recommend?
In summary, Dr. Poeck said that it is important to “budget” well, particularly with antibiotic administration, and to strive for calculated therapy with as narrow a spectrum as possible. For patients who experience complications such as cytokine release syndrome as a reaction to cell therapy, delaying the use of antibiotics is important. However, it is often difficult to differentiate this syndrome from neutropenic fever. The aim should be to avoid high-risk antibiotics, if clinically justifiable. Patients should avoid taking antibiotics for 30 days before starting immunotherapy.
Regarding nutritional interventions, Dr. Poeck referred to the recent Onkopedia recommendation for nutrition after cancer and the 10 nutritional rules of the German Nutrition Society. According to Dr. Poeck, the important aspects of these recommendations are a fiber-rich diet (> 20 g/d) from various plant products and avoiding artificial sweeteners and flavorings, as well as ultraprocessed (convenience) foods. In addition, meat should be consumed only in moderation, and as little processed meat as possible should be consumed. In addition, regular (aerobic and anaerobic) physical activity is important.
“Looking ahead into the future,” said Dr. Poeck, “we need a uniform and functional understanding and we need a randomized prediction for diagnosis.”
This article was translated from the Medscape German edition.
A version of this article appeared on Medscape.com.
HAMBURG, Germany — The human microbiome comprises 39 to 44 billion microbes. That is ten times more than the number of cells in our body. Hendrik Poeck, MD, managing senior physician of internal medicine at the University Hospital Regensburg, illustrated this point at the annual meeting of the German Society for Hematology and Medical Oncology. If the gut microbiome falls out of balance, then “intestinal dysbiosis potentially poses a risk for the pathogenesis of local and systemic diseases,” explained Dr. Poeck.
Cancers and their therapies can also be influenced in this way. said Dr. Poeck.
Microbial diversity could be beneficial for cancer therapy, too. The composition of the microbiome varies significantly from host to host and can mutate. These properties make it a target for precision microbiotics, which involves using the gut microbiome as a biomarker to predict various physical reactions and to develop individualized diets.
Microbiome and Pathogenesis
The body’s microbiome fulfills a barrier function, especially where the body is exposed to an external environment: at the epidermis and the internal mucous membranes, in the gastrointestinal tract, and in the lungs, chest, and urogenital system.
Association studies on humans and experimental manipulations on mouse models of cancer showed that certain microorganisms can have either protective or harmful effects on cancer development, on the progression of a malignant disease, and on the response to therapy.
A Master Regulator?
Disruptions of the microbial system in the gut, as occur during antibiotic therapy, can have significant effects on a patient’s response to immunotherapy. Taking antibiotics shortly before or after starting therapy with immune checkpoint inhibitors (ICIs) significantly affected both overall survival (OS) and progression-free survival (PFS), as reported in a recent review and meta-analysis, for example.
Proton pump inhibitors also affect the gut microbiome and reduce the response to immunotherapy; this effect was demonstrated by an analysis of data from more than 2700 cancer patients that was recently presented at the annual meeting of the European Society for Medical Oncology (ESMO).
The extent to which the gut microbiome influences the efficacy of an ICI or predicts said efficacy was examined in a retrospective analysis published in Science in 2018, which Dr. Poeck presented. Resistance to ICI correlated with the relative frequency of the bacteria Akkermansia muciniphila in the gut of patients with cancer. In mouse models, the researchers restored the efficacy of the PD-1 blockade through a stool transplant.
Predicting Immunotherapy Response
If A muciniphila is present, can the composition of the microbiome act as a predictor for an effective ICI therapy?
Laurence Zitvogel, MD, PhD, and her working group at the National Institute of Health and Medical Research in Villejuif, France, performed a prospective study in 338 patients with non–small cell lung cancer and examined the prognostic significance of the fecal bacteria A muciniphila (Akk). The “Akkerman status” (low Akk vs high Akk) in a patient’s stool correlated with an increased objective response rate and a longer OS, independently of PD-L1 expression, antibiotics, and performance status. The OS for low Akk was 13.4 months, vs 18.8 months for high Akk in first-line treatment.
These results are promising, said Dr. Poeck. But there is no one-size-fits-all solution. No conclusions can be drawn from one bacterium on the efficacy of therapies in humans, since “the entirety of the bacteria is decisive,” said Dr. Poeck. In addition to the gut microbiome, the composition of gut metabolites influences the response to immunotherapies, as shown in a study with ICI.
Therapeutic Interventions
One possible therapeutic intervention to restore the gut microbiome is fecal microbiota transplantation (FMT). In a phase 1 study presented by Dr. Poeck, FMT was effective in the treatment of 20 patients with melanoma with ICI in an advanced and treatment-naive stage. Seven days after the patients received FMT, the first cycle with anti-PD-1 immunotherapy was initiated, with a total administration of three to four cycles. After 12 weeks, most patients were in complete or partial remission, as evidenced on imaging.
However, FMT also carries some risks. Two cases of sepsis with multiresistant Escherichia coli occurred, as well as other serious infections. Since then, there has been an FDA condition for extended screening of the donor stool, said Dr. Poeck. Nevertheless, this intervention is promising. A search of the keywords “FMT in cancer/transplant setting” reveals 46 currently clinical studies on clinicaltrials.gov.
Nutritional Interventions
Dr. Poeck advises caution about over-the-counter products. These products usually contain only a few species, such as Lactobacillus and Bifidobacterium. “Over-the-counter probiotics can even delay the reconstitution of the microbiome after antibiotics,” said Dr. Poeck, according to a study. In some studies, the response rates were significantly lower after probiotic intake or led to controversial results, according to Dr. Poeck.
In contrast, Dr. Poeck said prebiotics (that is, a fiber-rich diet with indigestible carbohydrates) were promising. During digestion, prebiotics are split into short-chain fatty acids by bacterial enzymes and promote the growth of certain microbiota.
In this way, just 20 g of extremely fiber-rich food had a significant effect on PFS in 128 patients with melanoma undergoing anti-PD-1 immunotherapy. With 20 g of fiber-rich food per day, the PFS was stable over 60 months. The most significant benefit was observed in patients with a sufficient fiber intake who were not taking probiotics.
What to Recommend?
In summary, Dr. Poeck said that it is important to “budget” well, particularly with antibiotic administration, and to strive for calculated therapy with as narrow a spectrum as possible. For patients who experience complications such as cytokine release syndrome as a reaction to cell therapy, delaying the use of antibiotics is important. However, it is often difficult to differentiate this syndrome from neutropenic fever. The aim should be to avoid high-risk antibiotics, if clinically justifiable. Patients should avoid taking antibiotics for 30 days before starting immunotherapy.
Regarding nutritional interventions, Dr. Poeck referred to the recent Onkopedia recommendation for nutrition after cancer and the 10 nutritional rules of the German Nutrition Society. According to Dr. Poeck, the important aspects of these recommendations are a fiber-rich diet (> 20 g/d) from various plant products and avoiding artificial sweeteners and flavorings, as well as ultraprocessed (convenience) foods. In addition, meat should be consumed only in moderation, and as little processed meat as possible should be consumed. In addition, regular (aerobic and anaerobic) physical activity is important.
“Looking ahead into the future,” said Dr. Poeck, “we need a uniform and functional understanding and we need a randomized prediction for diagnosis.”
This article was translated from the Medscape German edition.
A version of this article appeared on Medscape.com.
Short, intense bursts of physical activity may cut cancer risk
The results of a recent study in JAMA Oncology suggest that This activity could be a promising measure for cancer prevention in people who otherwise find it difficult to exercise regularly.
Periods of intense, intermittent physical activity are short phases of strenuous physical exercise that normally last for 1 or 2 minutes, such as a short sprint for the bus or walking up the stairs. In the prospective cohort study conducted in a large group of unathletic adults, researchers investigated a potential dose-effect relationship between intense and daily intermittent physical activity and the cancer incidence rate.
Using data gathered from wearable arm trackers, the researchers analyzed the physical activity of 22,398 people with an average age of 62 years from the UK Biobank. Of these participants, 54.8% were women. After a median follow-up of 6.7 years, corresponding to 149,650 person-years, they determined the general cancer incidence rate in this cohort and the incidence rate of 13 kinds of cancer associated with minimal physical activity (physical-activity related cancers).
Over the study period, 2,356 cancer events occurred, of which 1,084 could be attributed to kinds of cancer associated with minimal physical activity. Nearly all of the intense physical activity (92.3%) was achieved in bursts of up to 1 minute.
Four minutes
The daily duration of activity was almost linearly associated with the outcome, wrote Emmanuel Stamatakis, PhD, professor of physical activity, lifestyle, and population health at the University of Sydney. “The dose-effect curve was more vertical, and the extent of the risk reduction for kinds of cancer associated with minimal activity was larger than for the overall cancer incidence rate.”
For example, the lowest dose of intense, intermittent physical activity of up to 1 minute was generally 3.4 minutes per day for cancer in general and 3.7 minutes per day for cancer associated with minimal activity (hazard ratio, 0.83 and 0.72, respectively).
“The results of the study with an average follow-up time of almost 7 years suggest that people with a little less than 4 minutes per day of sporadic intense activity had an overall 17% lower risk of cancer,” wrote Yvonne Wengström, PhD, professor of nursing at Karolinska Institutet in Stockholm, in an accompanying editorial.
For kinds of cancer possibly associated with minimal activity, the researchers found the risk to be reduced by 28% through daily intermittent physical activity. “Even a few minutes of short, intense physical exercise in people with less leisure activity could lower their cancer risk,” wrote Dr. Wengström and colleagues.
Only at the end of 2022 did the data from Dr. Stamatakis and his colleagues suggest a correlation between a little more than 4 minutes of intense physical activity per day and a lower risk for cardiovascular diseases, cancer, and overall mortality in athletes and nonathletes.
Wearable arm trackers
The authors of the recent study used an existing cohort’s activity data from an earlier substudy of the UK Biobank that measured acceleration in the wrist. The movement behavior here was recorded over a period of 7 days in more than 90,000 people between 2013 and 2015.
Dr. Wengström and her colleagues rated the arm trackers to be more reliable than the questionnaires that were completed by the subjects. “One strength of the present study is that physical activity was evaluated with the help of wrist acceleration meters, even though nonathletes were defined using the questionnaire data.”
Information about the general lifestyle of healthy living people also had to be included. Dr. Wengström believes that the researchers succeeded in this, because they adjusted the analyses for the following important factors:
- Age.
- Sex.
- Body mass index.
- Level of education.
- Smoking status.
- Alcohol consumption.
- Duration of sleep.
- Fruit and vegetable consumption.
- Medication intake.
- Parental cancer history.
Clinical implications
According to Dr. Wengström, more studies are required to see whether the results of this study can also be transferred to patients who already have a cancer disease. This is because patients with cancer such as premenopausal and postmenopausal women with breast cancer diseases, who have different biologies and hormonal environments, are affected differently by physical activity.
However, physical activity does play a role in patients with cancer “since physical fitness improves muscle strength, cancer-related fatigue, and the survivors’ quality of life,” said Dr. Wengström. However, it is still important to find the correct amount of physical activity for each group of patients and for each patient. Nevertheless, “any physical activity is better than none,” wrote Dr. Wengström and her colleagues.
This article was translated from Medscape’s German edition. A version of this article appeared on Medscape.com.
The results of a recent study in JAMA Oncology suggest that This activity could be a promising measure for cancer prevention in people who otherwise find it difficult to exercise regularly.
Periods of intense, intermittent physical activity are short phases of strenuous physical exercise that normally last for 1 or 2 minutes, such as a short sprint for the bus or walking up the stairs. In the prospective cohort study conducted in a large group of unathletic adults, researchers investigated a potential dose-effect relationship between intense and daily intermittent physical activity and the cancer incidence rate.
Using data gathered from wearable arm trackers, the researchers analyzed the physical activity of 22,398 people with an average age of 62 years from the UK Biobank. Of these participants, 54.8% were women. After a median follow-up of 6.7 years, corresponding to 149,650 person-years, they determined the general cancer incidence rate in this cohort and the incidence rate of 13 kinds of cancer associated with minimal physical activity (physical-activity related cancers).
Over the study period, 2,356 cancer events occurred, of which 1,084 could be attributed to kinds of cancer associated with minimal physical activity. Nearly all of the intense physical activity (92.3%) was achieved in bursts of up to 1 minute.
Four minutes
The daily duration of activity was almost linearly associated with the outcome, wrote Emmanuel Stamatakis, PhD, professor of physical activity, lifestyle, and population health at the University of Sydney. “The dose-effect curve was more vertical, and the extent of the risk reduction for kinds of cancer associated with minimal activity was larger than for the overall cancer incidence rate.”
For example, the lowest dose of intense, intermittent physical activity of up to 1 minute was generally 3.4 minutes per day for cancer in general and 3.7 minutes per day for cancer associated with minimal activity (hazard ratio, 0.83 and 0.72, respectively).
“The results of the study with an average follow-up time of almost 7 years suggest that people with a little less than 4 minutes per day of sporadic intense activity had an overall 17% lower risk of cancer,” wrote Yvonne Wengström, PhD, professor of nursing at Karolinska Institutet in Stockholm, in an accompanying editorial.
For kinds of cancer possibly associated with minimal activity, the researchers found the risk to be reduced by 28% through daily intermittent physical activity. “Even a few minutes of short, intense physical exercise in people with less leisure activity could lower their cancer risk,” wrote Dr. Wengström and colleagues.
Only at the end of 2022 did the data from Dr. Stamatakis and his colleagues suggest a correlation between a little more than 4 minutes of intense physical activity per day and a lower risk for cardiovascular diseases, cancer, and overall mortality in athletes and nonathletes.
Wearable arm trackers
The authors of the recent study used an existing cohort’s activity data from an earlier substudy of the UK Biobank that measured acceleration in the wrist. The movement behavior here was recorded over a period of 7 days in more than 90,000 people between 2013 and 2015.
Dr. Wengström and her colleagues rated the arm trackers to be more reliable than the questionnaires that were completed by the subjects. “One strength of the present study is that physical activity was evaluated with the help of wrist acceleration meters, even though nonathletes were defined using the questionnaire data.”
Information about the general lifestyle of healthy living people also had to be included. Dr. Wengström believes that the researchers succeeded in this, because they adjusted the analyses for the following important factors:
- Age.
- Sex.
- Body mass index.
- Level of education.
- Smoking status.
- Alcohol consumption.
- Duration of sleep.
- Fruit and vegetable consumption.
- Medication intake.
- Parental cancer history.
Clinical implications
According to Dr. Wengström, more studies are required to see whether the results of this study can also be transferred to patients who already have a cancer disease. This is because patients with cancer such as premenopausal and postmenopausal women with breast cancer diseases, who have different biologies and hormonal environments, are affected differently by physical activity.
However, physical activity does play a role in patients with cancer “since physical fitness improves muscle strength, cancer-related fatigue, and the survivors’ quality of life,” said Dr. Wengström. However, it is still important to find the correct amount of physical activity for each group of patients and for each patient. Nevertheless, “any physical activity is better than none,” wrote Dr. Wengström and her colleagues.
This article was translated from Medscape’s German edition. A version of this article appeared on Medscape.com.
The results of a recent study in JAMA Oncology suggest that This activity could be a promising measure for cancer prevention in people who otherwise find it difficult to exercise regularly.
Periods of intense, intermittent physical activity are short phases of strenuous physical exercise that normally last for 1 or 2 minutes, such as a short sprint for the bus or walking up the stairs. In the prospective cohort study conducted in a large group of unathletic adults, researchers investigated a potential dose-effect relationship between intense and daily intermittent physical activity and the cancer incidence rate.
Using data gathered from wearable arm trackers, the researchers analyzed the physical activity of 22,398 people with an average age of 62 years from the UK Biobank. Of these participants, 54.8% were women. After a median follow-up of 6.7 years, corresponding to 149,650 person-years, they determined the general cancer incidence rate in this cohort and the incidence rate of 13 kinds of cancer associated with minimal physical activity (physical-activity related cancers).
Over the study period, 2,356 cancer events occurred, of which 1,084 could be attributed to kinds of cancer associated with minimal physical activity. Nearly all of the intense physical activity (92.3%) was achieved in bursts of up to 1 minute.
Four minutes
The daily duration of activity was almost linearly associated with the outcome, wrote Emmanuel Stamatakis, PhD, professor of physical activity, lifestyle, and population health at the University of Sydney. “The dose-effect curve was more vertical, and the extent of the risk reduction for kinds of cancer associated with minimal activity was larger than for the overall cancer incidence rate.”
For example, the lowest dose of intense, intermittent physical activity of up to 1 minute was generally 3.4 minutes per day for cancer in general and 3.7 minutes per day for cancer associated with minimal activity (hazard ratio, 0.83 and 0.72, respectively).
“The results of the study with an average follow-up time of almost 7 years suggest that people with a little less than 4 minutes per day of sporadic intense activity had an overall 17% lower risk of cancer,” wrote Yvonne Wengström, PhD, professor of nursing at Karolinska Institutet in Stockholm, in an accompanying editorial.
For kinds of cancer possibly associated with minimal activity, the researchers found the risk to be reduced by 28% through daily intermittent physical activity. “Even a few minutes of short, intense physical exercise in people with less leisure activity could lower their cancer risk,” wrote Dr. Wengström and colleagues.
Only at the end of 2022 did the data from Dr. Stamatakis and his colleagues suggest a correlation between a little more than 4 minutes of intense physical activity per day and a lower risk for cardiovascular diseases, cancer, and overall mortality in athletes and nonathletes.
Wearable arm trackers
The authors of the recent study used an existing cohort’s activity data from an earlier substudy of the UK Biobank that measured acceleration in the wrist. The movement behavior here was recorded over a period of 7 days in more than 90,000 people between 2013 and 2015.
Dr. Wengström and her colleagues rated the arm trackers to be more reliable than the questionnaires that were completed by the subjects. “One strength of the present study is that physical activity was evaluated with the help of wrist acceleration meters, even though nonathletes were defined using the questionnaire data.”
Information about the general lifestyle of healthy living people also had to be included. Dr. Wengström believes that the researchers succeeded in this, because they adjusted the analyses for the following important factors:
- Age.
- Sex.
- Body mass index.
- Level of education.
- Smoking status.
- Alcohol consumption.
- Duration of sleep.
- Fruit and vegetable consumption.
- Medication intake.
- Parental cancer history.
Clinical implications
According to Dr. Wengström, more studies are required to see whether the results of this study can also be transferred to patients who already have a cancer disease. This is because patients with cancer such as premenopausal and postmenopausal women with breast cancer diseases, who have different biologies and hormonal environments, are affected differently by physical activity.
However, physical activity does play a role in patients with cancer “since physical fitness improves muscle strength, cancer-related fatigue, and the survivors’ quality of life,” said Dr. Wengström. However, it is still important to find the correct amount of physical activity for each group of patients and for each patient. Nevertheless, “any physical activity is better than none,” wrote Dr. Wengström and her colleagues.
This article was translated from Medscape’s German edition. A version of this article appeared on Medscape.com.
FROM JAMA ONCOLOGY
New German guidelines change the paradigm for asthma
Asthma has long been associated with the use of inhalers to control symptoms. The new S2K guideline on the management of asthma, compiled by experts and published in March 2023, aims to change this. “For decades, we have known about medication that can be used to put asthma into remission. The patient can go out or travel on vacation without an inhaler. This is possible. This is a symptom-prevention approach,” said the guideline coordinator Marek Lommatzsch, MD, PhD, head senior physician of the pulmonology department at the University Medicine Rostock, Germany, in an interview.
The guideline was created by the German Respiratory Society, and a further 11 professional societies from Germany and Austria were involved in the update. The authors comprehensively revised the guideline from 2017, and the evidence-based national disease management guideline (NVL) for general asthma care from 2020 was amended.
Erika von Mutius, MD, PhD, pediatrician and professor of pediatric allergology and pulmonology at the Dr. Von Hauner Children’s Hospital, Munich, and director of the Institute of Asthma and Allergy Prevention at Helmholtz Munich, was not directly involved in the guideline. She said,
Anti-inflammatory therapy
The significance of anti-inflammatory therapy was stressed in the NVL from 2020. The new guideline holds that anti-inflammatory therapy should be considered the primary therapeutic option. “We are making a U-turn: only treat the respiratory inflammation. Salbutamol should still only be given in exceptional cases as required,” according to Dr. Lommatzsch.
In the guideline, asthma therapy is described using an updated step-by-step plan. Inhaled glucocorticoids (ICS) represent the most important pillar of therapy. ICS can be used as permanent therapy or as as-needed therapy in fixed combination with formoterol, which rapidly dilates the airways.
Allergen immunotherapy, also known as hyposensitization, and biologics are also effective anti-inflammatory treatments, Dr. Lommatzsch added. “We must ensure that these anti-inflammatory medicines are also used effectively. Mild to moderate forms of asthma can be treated easily by a primary care physician,” he said. Basic diagnostics in the form of a blood sample are required. A somewhat more comprehensive medical history is also needed. “It takes a little more time and involves more than just taking the inhaler out of the cupboard.”
The situation regarding children, however, is a little different with regard to anti-inflammatory therapy, Dr. Von Mutius explained. “Childhood asthma has many forms, and confirming the diagnosis is not always straightforward, especially in infancy. If needed, salbutamol can be prescribed. However, the anti-inflammatory medication should usually also be administered.”
She emphasized that the guideline has been designed in a sophisticated way that offers the option of “using medical experience to see what is suitable for this family or better for this patient. This is still always subject to medical judgment and responsibility. I find this really successful.”
Diagnostics using biomarkers
The previous guideline concentrated on measuring lung function as a way of diagnosing asthmatic illness. Three biomarkers were brought to the fore:
- Eosinophils in the blood.
- IgE levels.
- The FeNO test (proportion of nitrogen monoxide in exhaled air).
Slightly amended, the guideline now states that the FeNO test is implemented as “an integral component of specialist diagnosis.”
The test measures the nitrogen monoxide content of exhaled air as an indicator of inflammation in the airways. However, this test must often be paid for by the patient. “In this respect, we want to give a nudge in the direction of the political decision-makers,” emphasized Dr. Lommatzsch.
Dr. Von Mutius added that use of the FeNO test has not been established in many practices and outpatient clinics. The inflammatory marker is also subject to fluctuations. “This is an update to the guideline where we must wait to see the political response.”
Which biologic?
Despite treatment with the established therapies, the symptoms of asthma can persist in some people with severe forms of the condition. Biologics are highly effective for these patients and are preferable in the last stage of therapy to long-term therapy with oral steroids, which have numerous side effects. The current guideline provides an overview diagram to help decide which biologic is suitable for which patient.
“There are six biologics that can be used to treat severe asthma. Officially, almost any biologic can be taken into consideration for a patient, since the approvals overlap. Nevertheless, we know that certain patients benefit hugely from certain biologics. A targeted choice should therefore be made,” explained Dr. Lommatzsch.
Biologics were mentioned in the 2020 NVL but not to the great extent that they are in the latest version. “For the first time, we have created an overview diagram for the individual choice of biologic. With it, we have now set a standard,” said Dr. Lommatzsch.
Therapy with biologics has brought about rapid progress for adults. Dr. Von Mutius anticipates challenges in approving such therapeutics for pediatric treatment. “As is often the case, these therapies are not approved for young children. Meanwhile, dupilumab is approved for children aged 6 months and older; unfortunately, the indication for this is actually atopic dermatitis,” she explains.
When using this therapy for pediatric patients, it is therefore important to explain the options to parents and to inform them of side effects. Severe forms of asthma are rare in children; they are uncommon in adults but are more prevalent than in children.
Children and adolescents
One new chapter in the guideline describes giving medical advice to adolescents choosing a career. A table has been compiled that contains information regarding jobs and their respective allergy and asthma risk. The table is designed to be displayed in a medical practice.
Another chapter characterizes the interrelation between asthma and mental health. It differentiates between psychiatric comorbidities for which the patient requires professional help and the stress caused by the asthmatic illness itself. Many patients do not have a mental illness but do suffer under the everyday strain of having asthma, said Dr. Lommatzsch. Therefore, it is important to educate patients and their relatives on how to make a strength out of this supposed weakness – the asthmatic illness. “We have established a procedure for this and have summarized its key points in the guideline,” said Dr. Lommatzsch.
Other updates to the guideline cover asthma in different contexts, such as in pregnant women. The updates address adrenal insufficiency as a side effect of the use of steroids over many years. In addition, the guideline contains a chapter on digital apps that can help with diagnostics and medical history.
Dr. Lommatzsch highlighted a new tool. “By using 15 key points summarized in a table, the guideline displays the essential differences between COPD [chronic obstructive pulmonary disease] and asthma in terms of the symptoms and the findings. It is the most modern table available in Germany that differentiates between the two diseases.”
This article was translated from the Medscape German Edition and a version appeared on Medscape.com.
Asthma has long been associated with the use of inhalers to control symptoms. The new S2K guideline on the management of asthma, compiled by experts and published in March 2023, aims to change this. “For decades, we have known about medication that can be used to put asthma into remission. The patient can go out or travel on vacation without an inhaler. This is possible. This is a symptom-prevention approach,” said the guideline coordinator Marek Lommatzsch, MD, PhD, head senior physician of the pulmonology department at the University Medicine Rostock, Germany, in an interview.
The guideline was created by the German Respiratory Society, and a further 11 professional societies from Germany and Austria were involved in the update. The authors comprehensively revised the guideline from 2017, and the evidence-based national disease management guideline (NVL) for general asthma care from 2020 was amended.
Erika von Mutius, MD, PhD, pediatrician and professor of pediatric allergology and pulmonology at the Dr. Von Hauner Children’s Hospital, Munich, and director of the Institute of Asthma and Allergy Prevention at Helmholtz Munich, was not directly involved in the guideline. She said,
Anti-inflammatory therapy
The significance of anti-inflammatory therapy was stressed in the NVL from 2020. The new guideline holds that anti-inflammatory therapy should be considered the primary therapeutic option. “We are making a U-turn: only treat the respiratory inflammation. Salbutamol should still only be given in exceptional cases as required,” according to Dr. Lommatzsch.
In the guideline, asthma therapy is described using an updated step-by-step plan. Inhaled glucocorticoids (ICS) represent the most important pillar of therapy. ICS can be used as permanent therapy or as as-needed therapy in fixed combination with formoterol, which rapidly dilates the airways.
Allergen immunotherapy, also known as hyposensitization, and biologics are also effective anti-inflammatory treatments, Dr. Lommatzsch added. “We must ensure that these anti-inflammatory medicines are also used effectively. Mild to moderate forms of asthma can be treated easily by a primary care physician,” he said. Basic diagnostics in the form of a blood sample are required. A somewhat more comprehensive medical history is also needed. “It takes a little more time and involves more than just taking the inhaler out of the cupboard.”
The situation regarding children, however, is a little different with regard to anti-inflammatory therapy, Dr. Von Mutius explained. “Childhood asthma has many forms, and confirming the diagnosis is not always straightforward, especially in infancy. If needed, salbutamol can be prescribed. However, the anti-inflammatory medication should usually also be administered.”
She emphasized that the guideline has been designed in a sophisticated way that offers the option of “using medical experience to see what is suitable for this family or better for this patient. This is still always subject to medical judgment and responsibility. I find this really successful.”
Diagnostics using biomarkers
The previous guideline concentrated on measuring lung function as a way of diagnosing asthmatic illness. Three biomarkers were brought to the fore:
- Eosinophils in the blood.
- IgE levels.
- The FeNO test (proportion of nitrogen monoxide in exhaled air).
Slightly amended, the guideline now states that the FeNO test is implemented as “an integral component of specialist diagnosis.”
The test measures the nitrogen monoxide content of exhaled air as an indicator of inflammation in the airways. However, this test must often be paid for by the patient. “In this respect, we want to give a nudge in the direction of the political decision-makers,” emphasized Dr. Lommatzsch.
Dr. Von Mutius added that use of the FeNO test has not been established in many practices and outpatient clinics. The inflammatory marker is also subject to fluctuations. “This is an update to the guideline where we must wait to see the political response.”
Which biologic?
Despite treatment with the established therapies, the symptoms of asthma can persist in some people with severe forms of the condition. Biologics are highly effective for these patients and are preferable in the last stage of therapy to long-term therapy with oral steroids, which have numerous side effects. The current guideline provides an overview diagram to help decide which biologic is suitable for which patient.
“There are six biologics that can be used to treat severe asthma. Officially, almost any biologic can be taken into consideration for a patient, since the approvals overlap. Nevertheless, we know that certain patients benefit hugely from certain biologics. A targeted choice should therefore be made,” explained Dr. Lommatzsch.
Biologics were mentioned in the 2020 NVL but not to the great extent that they are in the latest version. “For the first time, we have created an overview diagram for the individual choice of biologic. With it, we have now set a standard,” said Dr. Lommatzsch.
Therapy with biologics has brought about rapid progress for adults. Dr. Von Mutius anticipates challenges in approving such therapeutics for pediatric treatment. “As is often the case, these therapies are not approved for young children. Meanwhile, dupilumab is approved for children aged 6 months and older; unfortunately, the indication for this is actually atopic dermatitis,” she explains.
When using this therapy for pediatric patients, it is therefore important to explain the options to parents and to inform them of side effects. Severe forms of asthma are rare in children; they are uncommon in adults but are more prevalent than in children.
Children and adolescents
One new chapter in the guideline describes giving medical advice to adolescents choosing a career. A table has been compiled that contains information regarding jobs and their respective allergy and asthma risk. The table is designed to be displayed in a medical practice.
Another chapter characterizes the interrelation between asthma and mental health. It differentiates between psychiatric comorbidities for which the patient requires professional help and the stress caused by the asthmatic illness itself. Many patients do not have a mental illness but do suffer under the everyday strain of having asthma, said Dr. Lommatzsch. Therefore, it is important to educate patients and their relatives on how to make a strength out of this supposed weakness – the asthmatic illness. “We have established a procedure for this and have summarized its key points in the guideline,” said Dr. Lommatzsch.
Other updates to the guideline cover asthma in different contexts, such as in pregnant women. The updates address adrenal insufficiency as a side effect of the use of steroids over many years. In addition, the guideline contains a chapter on digital apps that can help with diagnostics and medical history.
Dr. Lommatzsch highlighted a new tool. “By using 15 key points summarized in a table, the guideline displays the essential differences between COPD [chronic obstructive pulmonary disease] and asthma in terms of the symptoms and the findings. It is the most modern table available in Germany that differentiates between the two diseases.”
This article was translated from the Medscape German Edition and a version appeared on Medscape.com.
Asthma has long been associated with the use of inhalers to control symptoms. The new S2K guideline on the management of asthma, compiled by experts and published in March 2023, aims to change this. “For decades, we have known about medication that can be used to put asthma into remission. The patient can go out or travel on vacation without an inhaler. This is possible. This is a symptom-prevention approach,” said the guideline coordinator Marek Lommatzsch, MD, PhD, head senior physician of the pulmonology department at the University Medicine Rostock, Germany, in an interview.
The guideline was created by the German Respiratory Society, and a further 11 professional societies from Germany and Austria were involved in the update. The authors comprehensively revised the guideline from 2017, and the evidence-based national disease management guideline (NVL) for general asthma care from 2020 was amended.
Erika von Mutius, MD, PhD, pediatrician and professor of pediatric allergology and pulmonology at the Dr. Von Hauner Children’s Hospital, Munich, and director of the Institute of Asthma and Allergy Prevention at Helmholtz Munich, was not directly involved in the guideline. She said,
Anti-inflammatory therapy
The significance of anti-inflammatory therapy was stressed in the NVL from 2020. The new guideline holds that anti-inflammatory therapy should be considered the primary therapeutic option. “We are making a U-turn: only treat the respiratory inflammation. Salbutamol should still only be given in exceptional cases as required,” according to Dr. Lommatzsch.
In the guideline, asthma therapy is described using an updated step-by-step plan. Inhaled glucocorticoids (ICS) represent the most important pillar of therapy. ICS can be used as permanent therapy or as as-needed therapy in fixed combination with formoterol, which rapidly dilates the airways.
Allergen immunotherapy, also known as hyposensitization, and biologics are also effective anti-inflammatory treatments, Dr. Lommatzsch added. “We must ensure that these anti-inflammatory medicines are also used effectively. Mild to moderate forms of asthma can be treated easily by a primary care physician,” he said. Basic diagnostics in the form of a blood sample are required. A somewhat more comprehensive medical history is also needed. “It takes a little more time and involves more than just taking the inhaler out of the cupboard.”
The situation regarding children, however, is a little different with regard to anti-inflammatory therapy, Dr. Von Mutius explained. “Childhood asthma has many forms, and confirming the diagnosis is not always straightforward, especially in infancy. If needed, salbutamol can be prescribed. However, the anti-inflammatory medication should usually also be administered.”
She emphasized that the guideline has been designed in a sophisticated way that offers the option of “using medical experience to see what is suitable for this family or better for this patient. This is still always subject to medical judgment and responsibility. I find this really successful.”
Diagnostics using biomarkers
The previous guideline concentrated on measuring lung function as a way of diagnosing asthmatic illness. Three biomarkers were brought to the fore:
- Eosinophils in the blood.
- IgE levels.
- The FeNO test (proportion of nitrogen monoxide in exhaled air).
Slightly amended, the guideline now states that the FeNO test is implemented as “an integral component of specialist diagnosis.”
The test measures the nitrogen monoxide content of exhaled air as an indicator of inflammation in the airways. However, this test must often be paid for by the patient. “In this respect, we want to give a nudge in the direction of the political decision-makers,” emphasized Dr. Lommatzsch.
Dr. Von Mutius added that use of the FeNO test has not been established in many practices and outpatient clinics. The inflammatory marker is also subject to fluctuations. “This is an update to the guideline where we must wait to see the political response.”
Which biologic?
Despite treatment with the established therapies, the symptoms of asthma can persist in some people with severe forms of the condition. Biologics are highly effective for these patients and are preferable in the last stage of therapy to long-term therapy with oral steroids, which have numerous side effects. The current guideline provides an overview diagram to help decide which biologic is suitable for which patient.
“There are six biologics that can be used to treat severe asthma. Officially, almost any biologic can be taken into consideration for a patient, since the approvals overlap. Nevertheless, we know that certain patients benefit hugely from certain biologics. A targeted choice should therefore be made,” explained Dr. Lommatzsch.
Biologics were mentioned in the 2020 NVL but not to the great extent that they are in the latest version. “For the first time, we have created an overview diagram for the individual choice of biologic. With it, we have now set a standard,” said Dr. Lommatzsch.
Therapy with biologics has brought about rapid progress for adults. Dr. Von Mutius anticipates challenges in approving such therapeutics for pediatric treatment. “As is often the case, these therapies are not approved for young children. Meanwhile, dupilumab is approved for children aged 6 months and older; unfortunately, the indication for this is actually atopic dermatitis,” she explains.
When using this therapy for pediatric patients, it is therefore important to explain the options to parents and to inform them of side effects. Severe forms of asthma are rare in children; they are uncommon in adults but are more prevalent than in children.
Children and adolescents
One new chapter in the guideline describes giving medical advice to adolescents choosing a career. A table has been compiled that contains information regarding jobs and their respective allergy and asthma risk. The table is designed to be displayed in a medical practice.
Another chapter characterizes the interrelation between asthma and mental health. It differentiates between psychiatric comorbidities for which the patient requires professional help and the stress caused by the asthmatic illness itself. Many patients do not have a mental illness but do suffer under the everyday strain of having asthma, said Dr. Lommatzsch. Therefore, it is important to educate patients and their relatives on how to make a strength out of this supposed weakness – the asthmatic illness. “We have established a procedure for this and have summarized its key points in the guideline,” said Dr. Lommatzsch.
Other updates to the guideline cover asthma in different contexts, such as in pregnant women. The updates address adrenal insufficiency as a side effect of the use of steroids over many years. In addition, the guideline contains a chapter on digital apps that can help with diagnostics and medical history.
Dr. Lommatzsch highlighted a new tool. “By using 15 key points summarized in a table, the guideline displays the essential differences between COPD [chronic obstructive pulmonary disease] and asthma in terms of the symptoms and the findings. It is the most modern table available in Germany that differentiates between the two diseases.”
This article was translated from the Medscape German Edition and a version appeared on Medscape.com.