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New acellular pertussis vaccine may solve waning immunogenicity problem
MADRID – A novel, monovalent, acellular pertussis vaccine containing a recombinant, genetically inactivated pertussis toxin displayed markedly greater sustained immunogenicity than the widely used Sanofi Pasteur Tdap, known as Adacel, which is used as a booster vaccination of adolescents and young adults, in a pivotal phase 3, randomized trial, Simonetta Viviani, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
“Our interpretation of these results is that they open up a new way to approach pertussis vaccination,” declared Dr. Viviani, director of clinical development at BioNet-Asia, a Bangkok-based biotech vaccine company.
The impetus for developing new acellular pertussis vaccines is the documented resurgence of pertussis.
“One suggested approach has been to replace chemically inactivated PT with a genetically inactivated PT. The rationale for that is the epitopes of the PT are conserved in the genetically modified PT toxin, as opposed to being destroyed in the chemical inactivation process,” Dr. Viviani explained.
The significant phase 3 trial included 450 Thai 12- to 17-year-olds who were randomized to a single 0.5-mL dose of Pertagen, Boostagen, or Adacel. Both Pertagen and Boostagen contain 5 mcg of the genetically inactivated PT and 5 mcg of filamentous hemagglutinin.
The seroconversion rate, defined as the proportion of subjects who reached at least a fourfold increase in titers of PT and filamentous-hemagglutinin antibodies over baseline, was far superior at both 28 days and 1 year in subjects who got Pertagen or Boostagen, compared with those who received Adacel.
Session chair Ulrich Heininger, MD, declared, “This is really, really exciting.”
It now will be very important that the monovalent Pertagen vaccine be formally studied in pregnant women, he observed.
“Since we’d like to immunize women in every pregnancy and they don’t necessarily need the Td component of Tdap every time, a monovalent vaccine might open a new path for acceptance,” commented Dr. Heininger, professor of pediatric infectious diseases at University Children’s Hospital in Basel, Switz.
Dr. Viviani said that a study in pregnant women is now in the early planning stages.
The study was sponsored by BioNet-Asia and Mahidol University. Dr. Viviani is a BioNet employee.
MADRID – A novel, monovalent, acellular pertussis vaccine containing a recombinant, genetically inactivated pertussis toxin displayed markedly greater sustained immunogenicity than the widely used Sanofi Pasteur Tdap, known as Adacel, which is used as a booster vaccination of adolescents and young adults, in a pivotal phase 3, randomized trial, Simonetta Viviani, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
“Our interpretation of these results is that they open up a new way to approach pertussis vaccination,” declared Dr. Viviani, director of clinical development at BioNet-Asia, a Bangkok-based biotech vaccine company.
The impetus for developing new acellular pertussis vaccines is the documented resurgence of pertussis.
“One suggested approach has been to replace chemically inactivated PT with a genetically inactivated PT. The rationale for that is the epitopes of the PT are conserved in the genetically modified PT toxin, as opposed to being destroyed in the chemical inactivation process,” Dr. Viviani explained.
The significant phase 3 trial included 450 Thai 12- to 17-year-olds who were randomized to a single 0.5-mL dose of Pertagen, Boostagen, or Adacel. Both Pertagen and Boostagen contain 5 mcg of the genetically inactivated PT and 5 mcg of filamentous hemagglutinin.
The seroconversion rate, defined as the proportion of subjects who reached at least a fourfold increase in titers of PT and filamentous-hemagglutinin antibodies over baseline, was far superior at both 28 days and 1 year in subjects who got Pertagen or Boostagen, compared with those who received Adacel.
Session chair Ulrich Heininger, MD, declared, “This is really, really exciting.”
It now will be very important that the monovalent Pertagen vaccine be formally studied in pregnant women, he observed.
“Since we’d like to immunize women in every pregnancy and they don’t necessarily need the Td component of Tdap every time, a monovalent vaccine might open a new path for acceptance,” commented Dr. Heininger, professor of pediatric infectious diseases at University Children’s Hospital in Basel, Switz.
Dr. Viviani said that a study in pregnant women is now in the early planning stages.
The study was sponsored by BioNet-Asia and Mahidol University. Dr. Viviani is a BioNet employee.
MADRID – A novel, monovalent, acellular pertussis vaccine containing a recombinant, genetically inactivated pertussis toxin displayed markedly greater sustained immunogenicity than the widely used Sanofi Pasteur Tdap, known as Adacel, which is used as a booster vaccination of adolescents and young adults, in a pivotal phase 3, randomized trial, Simonetta Viviani, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
“Our interpretation of these results is that they open up a new way to approach pertussis vaccination,” declared Dr. Viviani, director of clinical development at BioNet-Asia, a Bangkok-based biotech vaccine company.
The impetus for developing new acellular pertussis vaccines is the documented resurgence of pertussis.
“One suggested approach has been to replace chemically inactivated PT with a genetically inactivated PT. The rationale for that is the epitopes of the PT are conserved in the genetically modified PT toxin, as opposed to being destroyed in the chemical inactivation process,” Dr. Viviani explained.
The significant phase 3 trial included 450 Thai 12- to 17-year-olds who were randomized to a single 0.5-mL dose of Pertagen, Boostagen, or Adacel. Both Pertagen and Boostagen contain 5 mcg of the genetically inactivated PT and 5 mcg of filamentous hemagglutinin.
The seroconversion rate, defined as the proportion of subjects who reached at least a fourfold increase in titers of PT and filamentous-hemagglutinin antibodies over baseline, was far superior at both 28 days and 1 year in subjects who got Pertagen or Boostagen, compared with those who received Adacel.
Session chair Ulrich Heininger, MD, declared, “This is really, really exciting.”
It now will be very important that the monovalent Pertagen vaccine be formally studied in pregnant women, he observed.
“Since we’d like to immunize women in every pregnancy and they don’t necessarily need the Td component of Tdap every time, a monovalent vaccine might open a new path for acceptance,” commented Dr. Heininger, professor of pediatric infectious diseases at University Children’s Hospital in Basel, Switz.
Dr. Viviani said that a study in pregnant women is now in the early planning stages.
The study was sponsored by BioNet-Asia and Mahidol University. Dr. Viviani is a BioNet employee.
AT ESPID 2017
Key clinical point:
Major finding: One year after teens received a single dose of a novel acellular pertussis vaccine, they had a geometric mean titer of PT neutralizing antibody of 77 IU/mL, compared with just 12 IU/mL in adolescents who received a conventional Tdap vaccine.
Data source: This randomized, triple-arm, pivotal phase 3 clinical trial included 450 Thai 12- to 17-year-olds followed for 1 year after receiving a single dose of a novel monovalent pertussis vaccine or a novel Tdap vaccine, both of which contain genetically inactivated pertussis toxin, or, instead of those, a widely utilized conventional Tdap vaccine.
Disclosures: The study was sponsored by BioNet-Asia and Mahidol University. Dr. Viviani is a BioNet employee.
Elder Patients With Diabetes at Higher Risk for Cancer Surgery
Patients with diabetes—especially the elderly—are at high risk for morbidity and mortality due to cancer, studies have shown. Researchers from Specialist District Hospital and University of Rzeszow in Poland say their study “sheds some new light” in demonstrating another kind of association between diabetes and cancer in older patients: a higher risk of hospitalization with surgery due to cancer.
They analyzed data on 7,694 patients aged > 45 years hospitalized in a surgery ward. Of those, 652 were diagnosed with cancer and 370 with diabetes; 93 patients had both. The most common kind of cancer was urinary bladder cancer. The researchers note that their surgical unit has a large urology subdivision. Patients with other site-specific cancers are usually referred to more specialized clinical units.
Diabetes was the strongest predictor of risk among the variables analyzed, although urban residence also was a significant predictor. Risk of hospitalization due to cancer doubled among diabetic patients aged 45 to 65 years and was > 5 times higher among patients aged > 65 years, compared with the nondiabetic patients. The highest risk of hospitalization for site-specific cancers was among patients with kidney and breast cancers.
The researchers say their findings suggest that it is “advisable to make major efforts” for early detection and early radical treatment in older patients with diabetes.
Source:
Dᾳbrowski M, Grindecka A. Arch Med Sci. 2017;13(5):1025-1030.
doi: 10.5114/aoms.2016.58666.
Patients with diabetes—especially the elderly—are at high risk for morbidity and mortality due to cancer, studies have shown. Researchers from Specialist District Hospital and University of Rzeszow in Poland say their study “sheds some new light” in demonstrating another kind of association between diabetes and cancer in older patients: a higher risk of hospitalization with surgery due to cancer.
They analyzed data on 7,694 patients aged > 45 years hospitalized in a surgery ward. Of those, 652 were diagnosed with cancer and 370 with diabetes; 93 patients had both. The most common kind of cancer was urinary bladder cancer. The researchers note that their surgical unit has a large urology subdivision. Patients with other site-specific cancers are usually referred to more specialized clinical units.
Diabetes was the strongest predictor of risk among the variables analyzed, although urban residence also was a significant predictor. Risk of hospitalization due to cancer doubled among diabetic patients aged 45 to 65 years and was > 5 times higher among patients aged > 65 years, compared with the nondiabetic patients. The highest risk of hospitalization for site-specific cancers was among patients with kidney and breast cancers.
The researchers say their findings suggest that it is “advisable to make major efforts” for early detection and early radical treatment in older patients with diabetes.
Source:
Dᾳbrowski M, Grindecka A. Arch Med Sci. 2017;13(5):1025-1030.
doi: 10.5114/aoms.2016.58666.
Patients with diabetes—especially the elderly—are at high risk for morbidity and mortality due to cancer, studies have shown. Researchers from Specialist District Hospital and University of Rzeszow in Poland say their study “sheds some new light” in demonstrating another kind of association between diabetes and cancer in older patients: a higher risk of hospitalization with surgery due to cancer.
They analyzed data on 7,694 patients aged > 45 years hospitalized in a surgery ward. Of those, 652 were diagnosed with cancer and 370 with diabetes; 93 patients had both. The most common kind of cancer was urinary bladder cancer. The researchers note that their surgical unit has a large urology subdivision. Patients with other site-specific cancers are usually referred to more specialized clinical units.
Diabetes was the strongest predictor of risk among the variables analyzed, although urban residence also was a significant predictor. Risk of hospitalization due to cancer doubled among diabetic patients aged 45 to 65 years and was > 5 times higher among patients aged > 65 years, compared with the nondiabetic patients. The highest risk of hospitalization for site-specific cancers was among patients with kidney and breast cancers.
The researchers say their findings suggest that it is “advisable to make major efforts” for early detection and early radical treatment in older patients with diabetes.
Source:
Dᾳbrowski M, Grindecka A. Arch Med Sci. 2017;13(5):1025-1030.
doi: 10.5114/aoms.2016.58666.
Obinutuzumab-CHOP not superior to rituximab-CHOP in new DLBCL
Obinutuzumab with CHOP therapy did not improve progression-free survival, compared with rituximab plus CHOP, in patients with previously untreated diffuse large B-cell lymphoma (DLBCL), according to results from a phase 3 trial published in the Journal of Clinical Oncology. (2017 Aug 10. doi: 10.1200/JCO.2017.73.3402)
The findings suggest that obinutuzumab, a glycoengineered, type II, anti-CD20 monoclonal antibody, might not offer a benefit over standard treatment with rituximab, an anti-CD20 monoclonal antibody, when used with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).
A total of 1,418 patients were enrolled at 207 centers in 29 countries in the GOYA trial and were randomly assigned to one regimen or the other. The mean duration of exposure to the drugs was 25 weeks for both. The progression-free survival was 69.6% for obinutuzumab-CHOP – also known as G-CHOP – and 66.9% for rituximab-CHOP, not a statistically significant difference, wrote Umberto Vitolo, MD, of University-Hospital Città della Salute e della Scienza, Torino, Italy, and his fellow investigators.
The rate of adverse events was similar between the two groups. The lack of superiority of obinutuzumab comes after findings of its superiority in untreated follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). The investigators suggested that this may be a sign that obinutuzumab’s efficacy is best seen in less aggressive disease types.
“Given the advantages of G-based therapy in patients with FL and CLL, the lack of benefit of G-CHOP in patients with DLBCL in the GOYA study was unexpected, and the reasons for it are unclear,” they wrote. “This lack of benefit might simply have resulted from the differences in biologic and clinical profiles between indolent lymphoproliferative diseases, such as FL and CLL, and aggressive ones, such as DLBCL.”
The study was sponsored by F. Hoffman-La Roche, the manufacturer of the two drugs, and had support from Fondazione Italiana Linfomi.
Obinutuzumab with CHOP therapy did not improve progression-free survival, compared with rituximab plus CHOP, in patients with previously untreated diffuse large B-cell lymphoma (DLBCL), according to results from a phase 3 trial published in the Journal of Clinical Oncology. (2017 Aug 10. doi: 10.1200/JCO.2017.73.3402)
The findings suggest that obinutuzumab, a glycoengineered, type II, anti-CD20 monoclonal antibody, might not offer a benefit over standard treatment with rituximab, an anti-CD20 monoclonal antibody, when used with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).
A total of 1,418 patients were enrolled at 207 centers in 29 countries in the GOYA trial and were randomly assigned to one regimen or the other. The mean duration of exposure to the drugs was 25 weeks for both. The progression-free survival was 69.6% for obinutuzumab-CHOP – also known as G-CHOP – and 66.9% for rituximab-CHOP, not a statistically significant difference, wrote Umberto Vitolo, MD, of University-Hospital Città della Salute e della Scienza, Torino, Italy, and his fellow investigators.
The rate of adverse events was similar between the two groups. The lack of superiority of obinutuzumab comes after findings of its superiority in untreated follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). The investigators suggested that this may be a sign that obinutuzumab’s efficacy is best seen in less aggressive disease types.
“Given the advantages of G-based therapy in patients with FL and CLL, the lack of benefit of G-CHOP in patients with DLBCL in the GOYA study was unexpected, and the reasons for it are unclear,” they wrote. “This lack of benefit might simply have resulted from the differences in biologic and clinical profiles between indolent lymphoproliferative diseases, such as FL and CLL, and aggressive ones, such as DLBCL.”
The study was sponsored by F. Hoffman-La Roche, the manufacturer of the two drugs, and had support from Fondazione Italiana Linfomi.
Obinutuzumab with CHOP therapy did not improve progression-free survival, compared with rituximab plus CHOP, in patients with previously untreated diffuse large B-cell lymphoma (DLBCL), according to results from a phase 3 trial published in the Journal of Clinical Oncology. (2017 Aug 10. doi: 10.1200/JCO.2017.73.3402)
The findings suggest that obinutuzumab, a glycoengineered, type II, anti-CD20 monoclonal antibody, might not offer a benefit over standard treatment with rituximab, an anti-CD20 monoclonal antibody, when used with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).
A total of 1,418 patients were enrolled at 207 centers in 29 countries in the GOYA trial and were randomly assigned to one regimen or the other. The mean duration of exposure to the drugs was 25 weeks for both. The progression-free survival was 69.6% for obinutuzumab-CHOP – also known as G-CHOP – and 66.9% for rituximab-CHOP, not a statistically significant difference, wrote Umberto Vitolo, MD, of University-Hospital Città della Salute e della Scienza, Torino, Italy, and his fellow investigators.
The rate of adverse events was similar between the two groups. The lack of superiority of obinutuzumab comes after findings of its superiority in untreated follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). The investigators suggested that this may be a sign that obinutuzumab’s efficacy is best seen in less aggressive disease types.
“Given the advantages of G-based therapy in patients with FL and CLL, the lack of benefit of G-CHOP in patients with DLBCL in the GOYA study was unexpected, and the reasons for it are unclear,” they wrote. “This lack of benefit might simply have resulted from the differences in biologic and clinical profiles between indolent lymphoproliferative diseases, such as FL and CLL, and aggressive ones, such as DLBCL.”
The study was sponsored by F. Hoffman-La Roche, the manufacturer of the two drugs, and had support from Fondazione Italiana Linfomi.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Obinutuzumab with CHOP therapy did not improve progression-free survival for diffuse large B-cell lymphoma, compared with standard treatment with rituximab used with CHOP.
Major finding: The estimated PFS was 69.6% for obinutuzumab-CHOP and 66.9% for rituximab-CHOP, an insignificant difference.
Data source: A randomized phase 3 trial of 1,418 patients at 207 centers in 29 countries.
Disclosures: The study was sponsored by F. Hoffman-La Roche, the manufacturer of the two drugs, and had support from Fondazione Italiana Linfomi..
Calculating the Risk of Parkinson-Related Cognitive Deficits
Currently, treatments for Parkinson disease are only effective in improving motor deficits. But the loss of cognitive abilities is just as devastating. About 25% of patients also experience cognitive deficits that impair function. One problem in developing treatments, however, is that patients with cognitive effects vary widely. Being able to predict the chance that someone with Parkinson disease will develop cognitive deficits could be a useful tool, say researchers from Brigham and Women’s Hospital in Boston, Massachusetts, who conducted a study partly funded by the National Institute Neurological Disorders and Stroke. They think they might have created just the tool: a computer-based risk calculator.
The researchers combined data from 3,200 patients with Parkinson disease, representing more than 25,000 individual clinical assessments. They evaluated 7 known clinical and genetic risk factors associated with developing dementia, then used the information to build the risk calculator.
“By allowing clinical researchers to identify and select only patients at high risk for developing dementia, this tool could help in the design of ‘smarter’ trials that require a manageable number of participating patients,” said Clemens Scherzer, MD, the lead investigator.
By improving clinical trial design, the risk calculator could first help in the discovery of new treatments, the researchers say, then help determine which patients would benefit most from those treatments. “Prediction is the first step,” said Dr. Scherzer. “Prevention is the ultimate goal, preventing a dismal prognosis from ever happening.”
Currently, treatments for Parkinson disease are only effective in improving motor deficits. But the loss of cognitive abilities is just as devastating. About 25% of patients also experience cognitive deficits that impair function. One problem in developing treatments, however, is that patients with cognitive effects vary widely. Being able to predict the chance that someone with Parkinson disease will develop cognitive deficits could be a useful tool, say researchers from Brigham and Women’s Hospital in Boston, Massachusetts, who conducted a study partly funded by the National Institute Neurological Disorders and Stroke. They think they might have created just the tool: a computer-based risk calculator.
The researchers combined data from 3,200 patients with Parkinson disease, representing more than 25,000 individual clinical assessments. They evaluated 7 known clinical and genetic risk factors associated with developing dementia, then used the information to build the risk calculator.
“By allowing clinical researchers to identify and select only patients at high risk for developing dementia, this tool could help in the design of ‘smarter’ trials that require a manageable number of participating patients,” said Clemens Scherzer, MD, the lead investigator.
By improving clinical trial design, the risk calculator could first help in the discovery of new treatments, the researchers say, then help determine which patients would benefit most from those treatments. “Prediction is the first step,” said Dr. Scherzer. “Prevention is the ultimate goal, preventing a dismal prognosis from ever happening.”
Currently, treatments for Parkinson disease are only effective in improving motor deficits. But the loss of cognitive abilities is just as devastating. About 25% of patients also experience cognitive deficits that impair function. One problem in developing treatments, however, is that patients with cognitive effects vary widely. Being able to predict the chance that someone with Parkinson disease will develop cognitive deficits could be a useful tool, say researchers from Brigham and Women’s Hospital in Boston, Massachusetts, who conducted a study partly funded by the National Institute Neurological Disorders and Stroke. They think they might have created just the tool: a computer-based risk calculator.
The researchers combined data from 3,200 patients with Parkinson disease, representing more than 25,000 individual clinical assessments. They evaluated 7 known clinical and genetic risk factors associated with developing dementia, then used the information to build the risk calculator.
“By allowing clinical researchers to identify and select only patients at high risk for developing dementia, this tool could help in the design of ‘smarter’ trials that require a manageable number of participating patients,” said Clemens Scherzer, MD, the lead investigator.
By improving clinical trial design, the risk calculator could first help in the discovery of new treatments, the researchers say, then help determine which patients would benefit most from those treatments. “Prediction is the first step,” said Dr. Scherzer. “Prevention is the ultimate goal, preventing a dismal prognosis from ever happening.”
Inactivated quadrivalent influenza vaccine safe, effective in 6- to 35-month-olds
MADRID – An intramuscular inactivated quadrivalent influenza vaccine reduced the risk of laboratory-confirmed influenza by up to 69% in previously unvaccinated children aged 6-35 months in a large randomized trial, Stephanie Pepin, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
The quadrivalent influenza vaccine (QIV) is licensed by the Food and Drug Administration as Fluzone Quadrivalent for use in patients as young as 6 months of age. It contains two A- and two B-lineage influenza strains in order to address the common problem of mismatches between circulating influenza B and the single B-lineage strain included in trivalent vaccines.
The incidence of any laboratory confirmed strain of influenza illness during the period from 14 days post-vaccination to the end of flu season was 4.72% in the QIV group, compared with 9.84% in controls who received placebo, which translated to 52% efficacy. The incidence of influenza from vaccine-similar strains as determined by the Sanger sequencing method was 1.01% in children randomized to QIV, compared with 3.28% with placebo, for a 69% efficacy rate.
The QIV had a safety profile in this young population that was similar to the older licensed trivalent vaccine. The most frequently reported adverse reactions to the QIV were injection site pain, irritability, loss of appetite, abnormal crying, and malaise, each reported in 19%-25% of children after the first injection and in 14%-18% after the second. These were typically mild grade 1 or 2 reactions, which arose in the first 3 days after vaccination and resolved spontaneously 1-3 days later.
The trial was sponsored by Sanofi Pasteur and presented by a company employee.
MADRID – An intramuscular inactivated quadrivalent influenza vaccine reduced the risk of laboratory-confirmed influenza by up to 69% in previously unvaccinated children aged 6-35 months in a large randomized trial, Stephanie Pepin, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
The quadrivalent influenza vaccine (QIV) is licensed by the Food and Drug Administration as Fluzone Quadrivalent for use in patients as young as 6 months of age. It contains two A- and two B-lineage influenza strains in order to address the common problem of mismatches between circulating influenza B and the single B-lineage strain included in trivalent vaccines.
The incidence of any laboratory confirmed strain of influenza illness during the period from 14 days post-vaccination to the end of flu season was 4.72% in the QIV group, compared with 9.84% in controls who received placebo, which translated to 52% efficacy. The incidence of influenza from vaccine-similar strains as determined by the Sanger sequencing method was 1.01% in children randomized to QIV, compared with 3.28% with placebo, for a 69% efficacy rate.
The QIV had a safety profile in this young population that was similar to the older licensed trivalent vaccine. The most frequently reported adverse reactions to the QIV were injection site pain, irritability, loss of appetite, abnormal crying, and malaise, each reported in 19%-25% of children after the first injection and in 14%-18% after the second. These were typically mild grade 1 or 2 reactions, which arose in the first 3 days after vaccination and resolved spontaneously 1-3 days later.
The trial was sponsored by Sanofi Pasteur and presented by a company employee.
MADRID – An intramuscular inactivated quadrivalent influenza vaccine reduced the risk of laboratory-confirmed influenza by up to 69% in previously unvaccinated children aged 6-35 months in a large randomized trial, Stephanie Pepin, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
The quadrivalent influenza vaccine (QIV) is licensed by the Food and Drug Administration as Fluzone Quadrivalent for use in patients as young as 6 months of age. It contains two A- and two B-lineage influenza strains in order to address the common problem of mismatches between circulating influenza B and the single B-lineage strain included in trivalent vaccines.
The incidence of any laboratory confirmed strain of influenza illness during the period from 14 days post-vaccination to the end of flu season was 4.72% in the QIV group, compared with 9.84% in controls who received placebo, which translated to 52% efficacy. The incidence of influenza from vaccine-similar strains as determined by the Sanger sequencing method was 1.01% in children randomized to QIV, compared with 3.28% with placebo, for a 69% efficacy rate.
The QIV had a safety profile in this young population that was similar to the older licensed trivalent vaccine. The most frequently reported adverse reactions to the QIV were injection site pain, irritability, loss of appetite, abnormal crying, and malaise, each reported in 19%-25% of children after the first injection and in 14%-18% after the second. These were typically mild grade 1 or 2 reactions, which arose in the first 3 days after vaccination and resolved spontaneously 1-3 days later.
The trial was sponsored by Sanofi Pasteur and presented by a company employee.
AT ESPID 2017
Key clinical point:
Major finding: The intramuscular inactivated influenza vaccine, Fluzone Quadrivalent, reduced the risk of laboratory-confirmed influenza by up to 69% in 6- to 35-month-olds.
Data source: This randomized, multinational, placebo-controlled trial included 5,806 healthy 6- to 35-month-old children.
Disclosures: The study was sponsored by Sanofi Pasteur and presented by a company employee.
Physicians express mixed views on new FDA tobacco plan
Physicians associations are expressing mixed opinions about the Food and Drug Administration’s new plan for regulating tobacco products, such as flavored cigars, hookah tobacco, and e-cigarettes.
As part of the new plan, announced July 28, the FDA will relax previous application deadlines set for makers of newer tobacco products. The agency will also seek more public input on the role of flavors in tobacco products before moving forward with specific regulations.
“The delay outlined in [FDA Commissioner Scott Gottlieb’s] vision will cost the American public continued death and disease as a result of tobacco use,” Enid Neptune, MD, vice chair of the ATS Tobacco Action Committee said in the statement. “In short, Dr. Gottlieb’s announcement of the FDA’s new vision for regulating tobacco products is long on delay and short on action. The health of the American public, and particularly today’s youth, will suffer as a result of the FDA’s failure to act.”
The American College of Chest Physicians, meanwhile, applauded the FDA’s plan and expressed its support of the actions outlined.
“We welcome opportunities and actions that reduce tobacco use, addiction, and tobacco-related disease and death,” said Gerard Silvestri, MD, president for the college, in a statement. “We support the actions proposed by the FDA, which are likely to improve public health and reduce the burden of disease on patients and our country.”
As part of the FDA’s revised plan, the agency intends to begin a public dialogue about lowering nicotine levels in combustible cigarettes to nonaddictive levels through “achievable product standards.” The agency also plans to issue an advance notice of proposed rule making to seek input on the potential public health benefits and possible adverse effects of lowering nicotine in cigarettes.
Under revised time lines, applications for newly regulated combustible products, such as cigars, pipe tobacco, and hookah tobacco, must be submitted by makers to the FDA by Aug. 8, 2021, and applications for noncombustible products, such as e-cigarettes, must be submitted by Aug. 8, 2022. Manufacturers can continue to market their products while the agency reviews their product applications. The time frames push back previous deadlines that were established in a May 2016 final rule by the FDA. In the prior rule, manufacturers of all new tobacco products had 12-24 months to prepare and send applications for marketing authorization to the FDA and a 12-month continued compliance period after those dates in which to obtain FDA authorization.
“This comprehensive plan and sweeping approach to tobacco and nicotine allows the FDA to apply the powerful tools given by Congress to achieve the most significant public health impact,” Mitch Zeller, director of the FDA’s Center for Tobacco Products said in a statement. “Public input on these complex issues will help ensure the agency has the proper science-based policies in place to meaningfully reduce the harms caused by tobacco use.”
However, the ATS said that many of the issues raised in the FDA’s revised plan have already been discussed at length in the scientific literature and with the public.
“Scientific literature documenting the role cigars play in tobacco-related disease is extensive,” said Harold J. Farber, MD, chair of the ATS Tobacco Action Committee. “The FDA sought and received extensive public and industry input regarding exempting cigars during the proposed deeming rule. The FDA provided an extensive rational for why premium cigars should be regulated in its final deeming rule.”
In addition, the role of flavoring agents in tobacco products has also been discussed by the FDA, Dr. Neptune added. The agency previously sought, and received, extensive scientific, industry, and public input on the role of flavoring agents in tobacco products, she said. In addition, multiple reports have been issued on the role of flavoring agents, showing that flavoring agents increase tobacco initiation and make tobacco cessation harder, she noted.
“While more scientific information is always welcomed, Commissioner Gottlieb’s call for a new public discussion seeks to hide or ignore the extensive public discussion that has already occurred,” Dr. Neptune said. “In short, Commissioner Gottlieb has more than enough information to take action on flavored nicotine products today.”
agallegos@frontlinemedcom.com
On Twitter @legal_med
Physicians associations are expressing mixed opinions about the Food and Drug Administration’s new plan for regulating tobacco products, such as flavored cigars, hookah tobacco, and e-cigarettes.
As part of the new plan, announced July 28, the FDA will relax previous application deadlines set for makers of newer tobacco products. The agency will also seek more public input on the role of flavors in tobacco products before moving forward with specific regulations.
“The delay outlined in [FDA Commissioner Scott Gottlieb’s] vision will cost the American public continued death and disease as a result of tobacco use,” Enid Neptune, MD, vice chair of the ATS Tobacco Action Committee said in the statement. “In short, Dr. Gottlieb’s announcement of the FDA’s new vision for regulating tobacco products is long on delay and short on action. The health of the American public, and particularly today’s youth, will suffer as a result of the FDA’s failure to act.”
The American College of Chest Physicians, meanwhile, applauded the FDA’s plan and expressed its support of the actions outlined.
“We welcome opportunities and actions that reduce tobacco use, addiction, and tobacco-related disease and death,” said Gerard Silvestri, MD, president for the college, in a statement. “We support the actions proposed by the FDA, which are likely to improve public health and reduce the burden of disease on patients and our country.”
As part of the FDA’s revised plan, the agency intends to begin a public dialogue about lowering nicotine levels in combustible cigarettes to nonaddictive levels through “achievable product standards.” The agency also plans to issue an advance notice of proposed rule making to seek input on the potential public health benefits and possible adverse effects of lowering nicotine in cigarettes.
Under revised time lines, applications for newly regulated combustible products, such as cigars, pipe tobacco, and hookah tobacco, must be submitted by makers to the FDA by Aug. 8, 2021, and applications for noncombustible products, such as e-cigarettes, must be submitted by Aug. 8, 2022. Manufacturers can continue to market their products while the agency reviews their product applications. The time frames push back previous deadlines that were established in a May 2016 final rule by the FDA. In the prior rule, manufacturers of all new tobacco products had 12-24 months to prepare and send applications for marketing authorization to the FDA and a 12-month continued compliance period after those dates in which to obtain FDA authorization.
“This comprehensive plan and sweeping approach to tobacco and nicotine allows the FDA to apply the powerful tools given by Congress to achieve the most significant public health impact,” Mitch Zeller, director of the FDA’s Center for Tobacco Products said in a statement. “Public input on these complex issues will help ensure the agency has the proper science-based policies in place to meaningfully reduce the harms caused by tobacco use.”
However, the ATS said that many of the issues raised in the FDA’s revised plan have already been discussed at length in the scientific literature and with the public.
“Scientific literature documenting the role cigars play in tobacco-related disease is extensive,” said Harold J. Farber, MD, chair of the ATS Tobacco Action Committee. “The FDA sought and received extensive public and industry input regarding exempting cigars during the proposed deeming rule. The FDA provided an extensive rational for why premium cigars should be regulated in its final deeming rule.”
In addition, the role of flavoring agents in tobacco products has also been discussed by the FDA, Dr. Neptune added. The agency previously sought, and received, extensive scientific, industry, and public input on the role of flavoring agents in tobacco products, she said. In addition, multiple reports have been issued on the role of flavoring agents, showing that flavoring agents increase tobacco initiation and make tobacco cessation harder, she noted.
“While more scientific information is always welcomed, Commissioner Gottlieb’s call for a new public discussion seeks to hide or ignore the extensive public discussion that has already occurred,” Dr. Neptune said. “In short, Commissioner Gottlieb has more than enough information to take action on flavored nicotine products today.”
agallegos@frontlinemedcom.com
On Twitter @legal_med
Physicians associations are expressing mixed opinions about the Food and Drug Administration’s new plan for regulating tobacco products, such as flavored cigars, hookah tobacco, and e-cigarettes.
As part of the new plan, announced July 28, the FDA will relax previous application deadlines set for makers of newer tobacco products. The agency will also seek more public input on the role of flavors in tobacco products before moving forward with specific regulations.
“The delay outlined in [FDA Commissioner Scott Gottlieb’s] vision will cost the American public continued death and disease as a result of tobacco use,” Enid Neptune, MD, vice chair of the ATS Tobacco Action Committee said in the statement. “In short, Dr. Gottlieb’s announcement of the FDA’s new vision for regulating tobacco products is long on delay and short on action. The health of the American public, and particularly today’s youth, will suffer as a result of the FDA’s failure to act.”
The American College of Chest Physicians, meanwhile, applauded the FDA’s plan and expressed its support of the actions outlined.
“We welcome opportunities and actions that reduce tobacco use, addiction, and tobacco-related disease and death,” said Gerard Silvestri, MD, president for the college, in a statement. “We support the actions proposed by the FDA, which are likely to improve public health and reduce the burden of disease on patients and our country.”
As part of the FDA’s revised plan, the agency intends to begin a public dialogue about lowering nicotine levels in combustible cigarettes to nonaddictive levels through “achievable product standards.” The agency also plans to issue an advance notice of proposed rule making to seek input on the potential public health benefits and possible adverse effects of lowering nicotine in cigarettes.
Under revised time lines, applications for newly regulated combustible products, such as cigars, pipe tobacco, and hookah tobacco, must be submitted by makers to the FDA by Aug. 8, 2021, and applications for noncombustible products, such as e-cigarettes, must be submitted by Aug. 8, 2022. Manufacturers can continue to market their products while the agency reviews their product applications. The time frames push back previous deadlines that were established in a May 2016 final rule by the FDA. In the prior rule, manufacturers of all new tobacco products had 12-24 months to prepare and send applications for marketing authorization to the FDA and a 12-month continued compliance period after those dates in which to obtain FDA authorization.
“This comprehensive plan and sweeping approach to tobacco and nicotine allows the FDA to apply the powerful tools given by Congress to achieve the most significant public health impact,” Mitch Zeller, director of the FDA’s Center for Tobacco Products said in a statement. “Public input on these complex issues will help ensure the agency has the proper science-based policies in place to meaningfully reduce the harms caused by tobacco use.”
However, the ATS said that many of the issues raised in the FDA’s revised plan have already been discussed at length in the scientific literature and with the public.
“Scientific literature documenting the role cigars play in tobacco-related disease is extensive,” said Harold J. Farber, MD, chair of the ATS Tobacco Action Committee. “The FDA sought and received extensive public and industry input regarding exempting cigars during the proposed deeming rule. The FDA provided an extensive rational for why premium cigars should be regulated in its final deeming rule.”
In addition, the role of flavoring agents in tobacco products has also been discussed by the FDA, Dr. Neptune added. The agency previously sought, and received, extensive scientific, industry, and public input on the role of flavoring agents in tobacco products, she said. In addition, multiple reports have been issued on the role of flavoring agents, showing that flavoring agents increase tobacco initiation and make tobacco cessation harder, she noted.
“While more scientific information is always welcomed, Commissioner Gottlieb’s call for a new public discussion seeks to hide or ignore the extensive public discussion that has already occurred,” Dr. Neptune said. “In short, Commissioner Gottlieb has more than enough information to take action on flavored nicotine products today.”
agallegos@frontlinemedcom.com
On Twitter @legal_med
Crizotinib shows responses in pediatric ALCL and IMT
Treatment with the ALK-inhibitor crizotinib produced high response rates in pediatric patients with ALK-positive anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumors (IMTs), according to phase 2 trial results.
“The robust and sustained clinical responses to crizotinib in patients with relapsed or refractory ALK-driven ALCL and IMT highlight the importance of this oncogene and the sensitivity to ALK inhibition in these diseases,” said Yaël P. Mossé, MD, of Children’s Hospital of Philadelphia, and her associates.
Twenty-six patients with recurrent ALCL and 14 with unresectable IMTs – not older than 22 years – were enrolled. Six of the ALCL patients were treated at 165 mg/m2 (ALCL165) and 20 at 280 mg/m2 (ALCL280), which was found to be the recommended phase 2 dose. Ten of the ALCL280 patients had been treated at an equivalent to this dose in phase 1 and they were included in the phase 2 analysis. Those in the ALCL280 group tended to be older, at a median age of 12.2 years, than the other patients in the study, the investigators reported (J Clin Oncol. 2017 Aug 8 doi: 10.1200/JCO.2017.73.4830).
Eight of the IMT patients were enrolled in a dose-escalation portion of the study, with one receiving a 100 mg/m2 dose, one receiving 165 mg/m2, and the other six receiving 280 mg/m2. The other six were treated at 280 mg/m2. All of the IMT patient results are presented as one pool because those at the lower doses had toxicity and responses similar to those in patients given the higher dose.
Sixteen of 20 patients in the ALCL280 group – 80% – had a complete response, two had a partial response, and two were found to have stable disease. The median duration of treatment in this group was 0.4 years, and the median time to the first partial or complete response was 27 days. In the ALCL165 group, five of six, or 83%, had a complete response, along with one found to have stable disease. This group had a median treatment duration of 2.79 years, and the median time to the first partial or complete response was 26.5 days.
In the IMT group, 5 of 14, or 36%, had a complete response; 7, or 50%, had a partial response, and 2 had stable disease. They received treatment for a median of 1.63 years, and the median time to the first partial or complete response was 28.5 days.
Investigators reported that at least one grade 3 or 4 adverse event occurred in 83% of patients in the ALCL165 group, in all of the patients in the ALCL280 group, and in 71% in the IMT group. Adverse events considered possibly, probably, or definitely related to the study treatment occurred in 33% of the ALCL165 group, in 85% of the ALCL280 group, and in 57% of the IMT group. The most common adverse event was a decreased neutrophil count.
“Notable objective and sustained responses were observed in patients with ALK fusion-positive ALCL and IMT,” the investigators wrote, “establishing a precedent in pediatric oncology for studying the early-phase activity of a targeted agent in a biomarker-selected and histology-independent cohort of patients.
“In the cohort of patients with ALK-positive unresectable IMTs,” they continued, “ALK inhibition was a highly effective therapy and supports consideration of frontline therapy with crizotinib, a strategy that could also be relevant to adults with this rare disease.”
Treatment with the ALK-inhibitor crizotinib produced high response rates in pediatric patients with ALK-positive anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumors (IMTs), according to phase 2 trial results.
“The robust and sustained clinical responses to crizotinib in patients with relapsed or refractory ALK-driven ALCL and IMT highlight the importance of this oncogene and the sensitivity to ALK inhibition in these diseases,” said Yaël P. Mossé, MD, of Children’s Hospital of Philadelphia, and her associates.
Twenty-six patients with recurrent ALCL and 14 with unresectable IMTs – not older than 22 years – were enrolled. Six of the ALCL patients were treated at 165 mg/m2 (ALCL165) and 20 at 280 mg/m2 (ALCL280), which was found to be the recommended phase 2 dose. Ten of the ALCL280 patients had been treated at an equivalent to this dose in phase 1 and they were included in the phase 2 analysis. Those in the ALCL280 group tended to be older, at a median age of 12.2 years, than the other patients in the study, the investigators reported (J Clin Oncol. 2017 Aug 8 doi: 10.1200/JCO.2017.73.4830).
Eight of the IMT patients were enrolled in a dose-escalation portion of the study, with one receiving a 100 mg/m2 dose, one receiving 165 mg/m2, and the other six receiving 280 mg/m2. The other six were treated at 280 mg/m2. All of the IMT patient results are presented as one pool because those at the lower doses had toxicity and responses similar to those in patients given the higher dose.
Sixteen of 20 patients in the ALCL280 group – 80% – had a complete response, two had a partial response, and two were found to have stable disease. The median duration of treatment in this group was 0.4 years, and the median time to the first partial or complete response was 27 days. In the ALCL165 group, five of six, or 83%, had a complete response, along with one found to have stable disease. This group had a median treatment duration of 2.79 years, and the median time to the first partial or complete response was 26.5 days.
In the IMT group, 5 of 14, or 36%, had a complete response; 7, or 50%, had a partial response, and 2 had stable disease. They received treatment for a median of 1.63 years, and the median time to the first partial or complete response was 28.5 days.
Investigators reported that at least one grade 3 or 4 adverse event occurred in 83% of patients in the ALCL165 group, in all of the patients in the ALCL280 group, and in 71% in the IMT group. Adverse events considered possibly, probably, or definitely related to the study treatment occurred in 33% of the ALCL165 group, in 85% of the ALCL280 group, and in 57% of the IMT group. The most common adverse event was a decreased neutrophil count.
“Notable objective and sustained responses were observed in patients with ALK fusion-positive ALCL and IMT,” the investigators wrote, “establishing a precedent in pediatric oncology for studying the early-phase activity of a targeted agent in a biomarker-selected and histology-independent cohort of patients.
“In the cohort of patients with ALK-positive unresectable IMTs,” they continued, “ALK inhibition was a highly effective therapy and supports consideration of frontline therapy with crizotinib, a strategy that could also be relevant to adults with this rare disease.”
Treatment with the ALK-inhibitor crizotinib produced high response rates in pediatric patients with ALK-positive anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumors (IMTs), according to phase 2 trial results.
“The robust and sustained clinical responses to crizotinib in patients with relapsed or refractory ALK-driven ALCL and IMT highlight the importance of this oncogene and the sensitivity to ALK inhibition in these diseases,” said Yaël P. Mossé, MD, of Children’s Hospital of Philadelphia, and her associates.
Twenty-six patients with recurrent ALCL and 14 with unresectable IMTs – not older than 22 years – were enrolled. Six of the ALCL patients were treated at 165 mg/m2 (ALCL165) and 20 at 280 mg/m2 (ALCL280), which was found to be the recommended phase 2 dose. Ten of the ALCL280 patients had been treated at an equivalent to this dose in phase 1 and they were included in the phase 2 analysis. Those in the ALCL280 group tended to be older, at a median age of 12.2 years, than the other patients in the study, the investigators reported (J Clin Oncol. 2017 Aug 8 doi: 10.1200/JCO.2017.73.4830).
Eight of the IMT patients were enrolled in a dose-escalation portion of the study, with one receiving a 100 mg/m2 dose, one receiving 165 mg/m2, and the other six receiving 280 mg/m2. The other six were treated at 280 mg/m2. All of the IMT patient results are presented as one pool because those at the lower doses had toxicity and responses similar to those in patients given the higher dose.
Sixteen of 20 patients in the ALCL280 group – 80% – had a complete response, two had a partial response, and two were found to have stable disease. The median duration of treatment in this group was 0.4 years, and the median time to the first partial or complete response was 27 days. In the ALCL165 group, five of six, or 83%, had a complete response, along with one found to have stable disease. This group had a median treatment duration of 2.79 years, and the median time to the first partial or complete response was 26.5 days.
In the IMT group, 5 of 14, or 36%, had a complete response; 7, or 50%, had a partial response, and 2 had stable disease. They received treatment for a median of 1.63 years, and the median time to the first partial or complete response was 28.5 days.
Investigators reported that at least one grade 3 or 4 adverse event occurred in 83% of patients in the ALCL165 group, in all of the patients in the ALCL280 group, and in 71% in the IMT group. Adverse events considered possibly, probably, or definitely related to the study treatment occurred in 33% of the ALCL165 group, in 85% of the ALCL280 group, and in 57% of the IMT group. The most common adverse event was a decreased neutrophil count.
“Notable objective and sustained responses were observed in patients with ALK fusion-positive ALCL and IMT,” the investigators wrote, “establishing a precedent in pediatric oncology for studying the early-phase activity of a targeted agent in a biomarker-selected and histology-independent cohort of patients.
“In the cohort of patients with ALK-positive unresectable IMTs,” they continued, “ALK inhibition was a highly effective therapy and supports consideration of frontline therapy with crizotinib, a strategy that could also be relevant to adults with this rare disease.”
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: The ALK-inhibitor crizotinib produced good responses in pediatric, relapsed/refractory ALK-positive anaplastic large cell lymphoma and unresectable inflammatory myofibroblastic tumors.
Major finding: Eighty percent of ALCL patients in the high-dose group had a complete response, along with 83% given the lower dose. In the IMT group, 36%, had a complete response.
Data source: A 26-patient trial with a two-stage design, including phase 2 results as well as some data from phase 1, conducted across four U.S. centers.
Disclosures: Several study authors reported financial conflicts, including stock or other ownership, speaking fees, or institutional research funding from Pfizer, Novartis, Johnson & Johnson and other companies.
Pertussis resurgence is real, but possible solutions exist
MADRID – The explanation for the ongoing resurgence in pertussis in adolescents and adults in the United States and other developed countries lies largely in the waning effectiveness of current acellular pertussis vaccines as early as 2-3 years post boosters, according to Stanley A. Plotkin, MD, chair of the steering committee for the Global Pertussis Initiative.
“The problem seems to lie in the lack of persistence of immunity after vaccination using the acellular pertussis vaccines. To say that this is not controversial would clearly be wrong, but that is my view,” he declared at the annual meeting of the European Society for Paediatric Infectious Diseases.
It’s a view supported by persuasive evidence, added Dr. Plotkin, emeritus professor of pediatrics at the University of Pennsylvania, Philadelphia.
In the United States, investigators at Northern California Kaiser Permanente have shown that the effectiveness of acellular pertussis in the Tdap vaccine wanes rapidly in adolescents. Indeed, it plunged from 69% effectiveness in the first year after vaccination to less than 9% by year 4 (Pediatrics. 2016 Mar;137[3]:e20153326).
In contrast, whole-cell pertussis vaccines provide roughly 6-10 years of protection against infection, and native infection provides persistent protection against reinfection for 7-20 years, Dr. Plotkin noted.
He was senior coauthor of a recent study that addresses why acellular pertussis vaccine immunity wanes so quickly. He and his coinvestigators demonstrated that while whole-cell pertussis vaccines promote vigorous Th1 and Th17 responses, which discourage pharyngeal colonization, acellular pertussis vaccines orient the immune system toward a less salutary Th1/Th2 response (Cold Spring Harb Perspect Biol. 2017 Mar 13. doi: 10.1101/cshperspect.a029454).
In addition, other investigators have shown that repeated booster doses of acellular pertussis vaccine generate higher levels of antigen-specific IgG4, which doesn’t bind complement and results in impaired phagocytosis and a suboptimal inflammatory response. In contrast, priming of the immune system via administration of a whole-cell pertussis vaccine at birth followed by acellular pertussis boosters results in improved phagocytosis and complement-mediated microbial killing via preferential induction of IgG1(Cold Spring Harb Perspect Biol. 2017 Mar 13. doi: 10.1101/cshperspect.a029553).
Possible solutions to the pertussis problem
Infants don’t need a new vaccine; that’s not where the vaccine failures are occurring. “Again, I stress that the problem so far has not been in infants, it has been in adolescents and adults,” he said.
A new vaccine is a daunting prospect. Given the huge investment vaccine manufacturers made in the 1990s to bring the current acellular vaccines to the market, they are hardly eager to launch development programs for new pertussis vaccines. They have other vaccine development priorities.
Moreover, the regulatory challenges are huge unless the Food and Drug Administration and other licensing authorities are willing to forgo the large, long, and expensive clinical trials that have traditionally been required. In lieu of such efficacy studies, they would need to consider studies demonstrating better immunogenicity based upon antibody titers, or animal studies.
“The possibility of a human challenge study in adults is an idea I like; I’m not sure about the FDA,” the pediatrician said.
Until a new or improved vaccine becomes available, the most important strategy to control the resurgence of pertussis is acellular vaccination of pregnant women in their third trimester to provide passive protection to the newborn via transplacental antibody. That practice is already recommended in the United States and many other countries. And while it reduces the risk of pertussis in early infancy – the most serious form of the disease – that strategy won’t have any real impact on the adult burden of disease, which Dr. Plotkin estimated at more than 600,000 cases annually.
Cocooning – a strategy of vaccinating all of a newborn’s family contacts – has been promoted in guidelines but has proved difficult to implement. “I think cocooning strategies by and large have been a failure,” he declared.
More frequent boosters of current acellular pertussis vaccines would presumably increase effectiveness, but that would be costly and tough to put in place on a public health scale.
A return to using conventional whole-cell pertussis vaccines would be a tough sell to the public and is probably flat out unacceptable. Developing a less reactogenic whole-cell vaccine might be a work-around, but it hasn’t been done yet.
The easiest way to improve acellular pertussis vaccine for adolescents and adults is to improve the pertussis toxin antigen component. Increasing the dose of pertussis toxin could generate more and longer-lasting antibodies to it. An even more exciting possibility is based upon evidence more than a decade old that genetic inactivation of pertussis toxin results in antibody levels far higher and presumably more bactericidal than the formalin-inactivated pertussis toxin included in current vaccines, according to Dr. Plotkin.
Adding stronger adjuvants to a Tdap vaccine for adolescents is another appealing strategy. There are plenty to choose from, including some that would presumably have an easier pathway to regulatory approval because they are already contained in licensed vaccines. This beefed-up adjuvant strategy, like the notion of changing the antigens in acellular pertussis vaccines to those from currently circulating strains, is feasible albeit more difficult than simply improving the pertussis toxin component of existing vaccines, he said.
The Global Pertussis Initiative is sponsored by Sanofi Pasteur. Dr. Plotkin reported serving as a consultant to that vaccine manufacturer and numerous others but declared he had no financial conflicts regarding his presentation.
MADRID – The explanation for the ongoing resurgence in pertussis in adolescents and adults in the United States and other developed countries lies largely in the waning effectiveness of current acellular pertussis vaccines as early as 2-3 years post boosters, according to Stanley A. Plotkin, MD, chair of the steering committee for the Global Pertussis Initiative.
“The problem seems to lie in the lack of persistence of immunity after vaccination using the acellular pertussis vaccines. To say that this is not controversial would clearly be wrong, but that is my view,” he declared at the annual meeting of the European Society for Paediatric Infectious Diseases.
It’s a view supported by persuasive evidence, added Dr. Plotkin, emeritus professor of pediatrics at the University of Pennsylvania, Philadelphia.
In the United States, investigators at Northern California Kaiser Permanente have shown that the effectiveness of acellular pertussis in the Tdap vaccine wanes rapidly in adolescents. Indeed, it plunged from 69% effectiveness in the first year after vaccination to less than 9% by year 4 (Pediatrics. 2016 Mar;137[3]:e20153326).
In contrast, whole-cell pertussis vaccines provide roughly 6-10 years of protection against infection, and native infection provides persistent protection against reinfection for 7-20 years, Dr. Plotkin noted.
He was senior coauthor of a recent study that addresses why acellular pertussis vaccine immunity wanes so quickly. He and his coinvestigators demonstrated that while whole-cell pertussis vaccines promote vigorous Th1 and Th17 responses, which discourage pharyngeal colonization, acellular pertussis vaccines orient the immune system toward a less salutary Th1/Th2 response (Cold Spring Harb Perspect Biol. 2017 Mar 13. doi: 10.1101/cshperspect.a029454).
In addition, other investigators have shown that repeated booster doses of acellular pertussis vaccine generate higher levels of antigen-specific IgG4, which doesn’t bind complement and results in impaired phagocytosis and a suboptimal inflammatory response. In contrast, priming of the immune system via administration of a whole-cell pertussis vaccine at birth followed by acellular pertussis boosters results in improved phagocytosis and complement-mediated microbial killing via preferential induction of IgG1(Cold Spring Harb Perspect Biol. 2017 Mar 13. doi: 10.1101/cshperspect.a029553).
Possible solutions to the pertussis problem
Infants don’t need a new vaccine; that’s not where the vaccine failures are occurring. “Again, I stress that the problem so far has not been in infants, it has been in adolescents and adults,” he said.
A new vaccine is a daunting prospect. Given the huge investment vaccine manufacturers made in the 1990s to bring the current acellular vaccines to the market, they are hardly eager to launch development programs for new pertussis vaccines. They have other vaccine development priorities.
Moreover, the regulatory challenges are huge unless the Food and Drug Administration and other licensing authorities are willing to forgo the large, long, and expensive clinical trials that have traditionally been required. In lieu of such efficacy studies, they would need to consider studies demonstrating better immunogenicity based upon antibody titers, or animal studies.
“The possibility of a human challenge study in adults is an idea I like; I’m not sure about the FDA,” the pediatrician said.
Until a new or improved vaccine becomes available, the most important strategy to control the resurgence of pertussis is acellular vaccination of pregnant women in their third trimester to provide passive protection to the newborn via transplacental antibody. That practice is already recommended in the United States and many other countries. And while it reduces the risk of pertussis in early infancy – the most serious form of the disease – that strategy won’t have any real impact on the adult burden of disease, which Dr. Plotkin estimated at more than 600,000 cases annually.
Cocooning – a strategy of vaccinating all of a newborn’s family contacts – has been promoted in guidelines but has proved difficult to implement. “I think cocooning strategies by and large have been a failure,” he declared.
More frequent boosters of current acellular pertussis vaccines would presumably increase effectiveness, but that would be costly and tough to put in place on a public health scale.
A return to using conventional whole-cell pertussis vaccines would be a tough sell to the public and is probably flat out unacceptable. Developing a less reactogenic whole-cell vaccine might be a work-around, but it hasn’t been done yet.
The easiest way to improve acellular pertussis vaccine for adolescents and adults is to improve the pertussis toxin antigen component. Increasing the dose of pertussis toxin could generate more and longer-lasting antibodies to it. An even more exciting possibility is based upon evidence more than a decade old that genetic inactivation of pertussis toxin results in antibody levels far higher and presumably more bactericidal than the formalin-inactivated pertussis toxin included in current vaccines, according to Dr. Plotkin.
Adding stronger adjuvants to a Tdap vaccine for adolescents is another appealing strategy. There are plenty to choose from, including some that would presumably have an easier pathway to regulatory approval because they are already contained in licensed vaccines. This beefed-up adjuvant strategy, like the notion of changing the antigens in acellular pertussis vaccines to those from currently circulating strains, is feasible albeit more difficult than simply improving the pertussis toxin component of existing vaccines, he said.
The Global Pertussis Initiative is sponsored by Sanofi Pasteur. Dr. Plotkin reported serving as a consultant to that vaccine manufacturer and numerous others but declared he had no financial conflicts regarding his presentation.
MADRID – The explanation for the ongoing resurgence in pertussis in adolescents and adults in the United States and other developed countries lies largely in the waning effectiveness of current acellular pertussis vaccines as early as 2-3 years post boosters, according to Stanley A. Plotkin, MD, chair of the steering committee for the Global Pertussis Initiative.
“The problem seems to lie in the lack of persistence of immunity after vaccination using the acellular pertussis vaccines. To say that this is not controversial would clearly be wrong, but that is my view,” he declared at the annual meeting of the European Society for Paediatric Infectious Diseases.
It’s a view supported by persuasive evidence, added Dr. Plotkin, emeritus professor of pediatrics at the University of Pennsylvania, Philadelphia.
In the United States, investigators at Northern California Kaiser Permanente have shown that the effectiveness of acellular pertussis in the Tdap vaccine wanes rapidly in adolescents. Indeed, it plunged from 69% effectiveness in the first year after vaccination to less than 9% by year 4 (Pediatrics. 2016 Mar;137[3]:e20153326).
In contrast, whole-cell pertussis vaccines provide roughly 6-10 years of protection against infection, and native infection provides persistent protection against reinfection for 7-20 years, Dr. Plotkin noted.
He was senior coauthor of a recent study that addresses why acellular pertussis vaccine immunity wanes so quickly. He and his coinvestigators demonstrated that while whole-cell pertussis vaccines promote vigorous Th1 and Th17 responses, which discourage pharyngeal colonization, acellular pertussis vaccines orient the immune system toward a less salutary Th1/Th2 response (Cold Spring Harb Perspect Biol. 2017 Mar 13. doi: 10.1101/cshperspect.a029454).
In addition, other investigators have shown that repeated booster doses of acellular pertussis vaccine generate higher levels of antigen-specific IgG4, which doesn’t bind complement and results in impaired phagocytosis and a suboptimal inflammatory response. In contrast, priming of the immune system via administration of a whole-cell pertussis vaccine at birth followed by acellular pertussis boosters results in improved phagocytosis and complement-mediated microbial killing via preferential induction of IgG1(Cold Spring Harb Perspect Biol. 2017 Mar 13. doi: 10.1101/cshperspect.a029553).
Possible solutions to the pertussis problem
Infants don’t need a new vaccine; that’s not where the vaccine failures are occurring. “Again, I stress that the problem so far has not been in infants, it has been in adolescents and adults,” he said.
A new vaccine is a daunting prospect. Given the huge investment vaccine manufacturers made in the 1990s to bring the current acellular vaccines to the market, they are hardly eager to launch development programs for new pertussis vaccines. They have other vaccine development priorities.
Moreover, the regulatory challenges are huge unless the Food and Drug Administration and other licensing authorities are willing to forgo the large, long, and expensive clinical trials that have traditionally been required. In lieu of such efficacy studies, they would need to consider studies demonstrating better immunogenicity based upon antibody titers, or animal studies.
“The possibility of a human challenge study in adults is an idea I like; I’m not sure about the FDA,” the pediatrician said.
Until a new or improved vaccine becomes available, the most important strategy to control the resurgence of pertussis is acellular vaccination of pregnant women in their third trimester to provide passive protection to the newborn via transplacental antibody. That practice is already recommended in the United States and many other countries. And while it reduces the risk of pertussis in early infancy – the most serious form of the disease – that strategy won’t have any real impact on the adult burden of disease, which Dr. Plotkin estimated at more than 600,000 cases annually.
Cocooning – a strategy of vaccinating all of a newborn’s family contacts – has been promoted in guidelines but has proved difficult to implement. “I think cocooning strategies by and large have been a failure,” he declared.
More frequent boosters of current acellular pertussis vaccines would presumably increase effectiveness, but that would be costly and tough to put in place on a public health scale.
A return to using conventional whole-cell pertussis vaccines would be a tough sell to the public and is probably flat out unacceptable. Developing a less reactogenic whole-cell vaccine might be a work-around, but it hasn’t been done yet.
The easiest way to improve acellular pertussis vaccine for adolescents and adults is to improve the pertussis toxin antigen component. Increasing the dose of pertussis toxin could generate more and longer-lasting antibodies to it. An even more exciting possibility is based upon evidence more than a decade old that genetic inactivation of pertussis toxin results in antibody levels far higher and presumably more bactericidal than the formalin-inactivated pertussis toxin included in current vaccines, according to Dr. Plotkin.
Adding stronger adjuvants to a Tdap vaccine for adolescents is another appealing strategy. There are plenty to choose from, including some that would presumably have an easier pathway to regulatory approval because they are already contained in licensed vaccines. This beefed-up adjuvant strategy, like the notion of changing the antigens in acellular pertussis vaccines to those from currently circulating strains, is feasible albeit more difficult than simply improving the pertussis toxin component of existing vaccines, he said.
The Global Pertussis Initiative is sponsored by Sanofi Pasteur. Dr. Plotkin reported serving as a consultant to that vaccine manufacturer and numerous others but declared he had no financial conflicts regarding his presentation.
EXPERT ANALYSIS FROM ESPID 2017
Legionnaires’ Disease in Health Care Settings
The CDC investigations of 27 outbreaks of Legionnaires’ disease between 2000 and 2014 found health care-associated Legionnaires’ disease accounted for 33% of the outbreaks, 57% of outbreak-associated cases, and 85% of outbreak-associated deaths. Nearly all were attributed to water system exposures that could have been prevented by effective water management programs.
In 2015, CDC researchers analyzed surveillance data from 20 states and the New York City metropolitan area that reported > 90% of confirmed legionellosis cases to the Supplemental Legionnaires’ Disease Surveillance System. Of 2,809 reported cases, 553 were health care associated. Definite cases accounted for 3%, and possible cases accounted for 17% of all the cases reported. Although only a small percentage were definitely related to health care settings, the fatality rate was high at 12%.
Of the 85 definite health care-associated Legionnaires’ disease cases, 80% were associated with long-term care facilities. Of the 468 possible cases, 13% were “possibly” associated with long-term care facilities, 49% with hospitals, and 26% with clinics.
The CDC says the number of definite cases and facilities reported is “likely an underestimate,” in part because of a lack of Legionella-specific testing. Another explanation is that hospital stays are typically shorter than the 10-day period used in the analysis.
One-fourth of patients with definite health care-associated Legionnaires’ disease die. Health care providers play a critical role in prevention and response, the CDC says, by rapidly identifying and reporting cases. Legionnaires’ disease is “clinically indistinguishable” from other causes of pneumonia, the researchers note. The preferred diagnostic method is to concurrently obtain a lower respiratory sputum sample for culture on selective media and a Legionella urinary antigen test.
In health care facilities, the researchers say, “prevention of the first case of Legionnaires’ disease is the ultimate goal.” The best way to do that, they advise, is to have an effective water management program. Guidelines for developing and monitoring programs are available at https://www.cdc.gov/legionella/WMPtoolkit.
The CDC investigations of 27 outbreaks of Legionnaires’ disease between 2000 and 2014 found health care-associated Legionnaires’ disease accounted for 33% of the outbreaks, 57% of outbreak-associated cases, and 85% of outbreak-associated deaths. Nearly all were attributed to water system exposures that could have been prevented by effective water management programs.
In 2015, CDC researchers analyzed surveillance data from 20 states and the New York City metropolitan area that reported > 90% of confirmed legionellosis cases to the Supplemental Legionnaires’ Disease Surveillance System. Of 2,809 reported cases, 553 were health care associated. Definite cases accounted for 3%, and possible cases accounted for 17% of all the cases reported. Although only a small percentage were definitely related to health care settings, the fatality rate was high at 12%.
Of the 85 definite health care-associated Legionnaires’ disease cases, 80% were associated with long-term care facilities. Of the 468 possible cases, 13% were “possibly” associated with long-term care facilities, 49% with hospitals, and 26% with clinics.
The CDC says the number of definite cases and facilities reported is “likely an underestimate,” in part because of a lack of Legionella-specific testing. Another explanation is that hospital stays are typically shorter than the 10-day period used in the analysis.
One-fourth of patients with definite health care-associated Legionnaires’ disease die. Health care providers play a critical role in prevention and response, the CDC says, by rapidly identifying and reporting cases. Legionnaires’ disease is “clinically indistinguishable” from other causes of pneumonia, the researchers note. The preferred diagnostic method is to concurrently obtain a lower respiratory sputum sample for culture on selective media and a Legionella urinary antigen test.
In health care facilities, the researchers say, “prevention of the first case of Legionnaires’ disease is the ultimate goal.” The best way to do that, they advise, is to have an effective water management program. Guidelines for developing and monitoring programs are available at https://www.cdc.gov/legionella/WMPtoolkit.
The CDC investigations of 27 outbreaks of Legionnaires’ disease between 2000 and 2014 found health care-associated Legionnaires’ disease accounted for 33% of the outbreaks, 57% of outbreak-associated cases, and 85% of outbreak-associated deaths. Nearly all were attributed to water system exposures that could have been prevented by effective water management programs.
In 2015, CDC researchers analyzed surveillance data from 20 states and the New York City metropolitan area that reported > 90% of confirmed legionellosis cases to the Supplemental Legionnaires’ Disease Surveillance System. Of 2,809 reported cases, 553 were health care associated. Definite cases accounted for 3%, and possible cases accounted for 17% of all the cases reported. Although only a small percentage were definitely related to health care settings, the fatality rate was high at 12%.
Of the 85 definite health care-associated Legionnaires’ disease cases, 80% were associated with long-term care facilities. Of the 468 possible cases, 13% were “possibly” associated with long-term care facilities, 49% with hospitals, and 26% with clinics.
The CDC says the number of definite cases and facilities reported is “likely an underestimate,” in part because of a lack of Legionella-specific testing. Another explanation is that hospital stays are typically shorter than the 10-day period used in the analysis.
One-fourth of patients with definite health care-associated Legionnaires’ disease die. Health care providers play a critical role in prevention and response, the CDC says, by rapidly identifying and reporting cases. Legionnaires’ disease is “clinically indistinguishable” from other causes of pneumonia, the researchers note. The preferred diagnostic method is to concurrently obtain a lower respiratory sputum sample for culture on selective media and a Legionella urinary antigen test.
In health care facilities, the researchers say, “prevention of the first case of Legionnaires’ disease is the ultimate goal.” The best way to do that, they advise, is to have an effective water management program. Guidelines for developing and monitoring programs are available at https://www.cdc.gov/legionella/WMPtoolkit.
Air pollution seen acting on stress hormones
Increases in stress hormone levels and other adverse metabolic changes accompany higher exposure to air pollution, Chinese researchers have found, while cutting indoor pollution levels appears to mitigate these effects.
Air pollution has been linked in epidemiological studies to increased risk of cardiovascular and metabolic diseases, but the mechanisms remain poorly understood. The new findings, published online Aug. 14 in Circulation, offer compelling evidence that air pollution may impact the central nervous system, and the hypothalamus-pituitary-adrenal axis especially (Circulation 2017 Aug 14;136:618-27).
The study design required that students spend as much time in their dorms as possible with the windows closed, though they could venture out for classes and exams. Fine particle concentration in the dorms treated by purifiers was 8.6 mcg per cubic meter during the study period, compared with a mean 101.4 outdoors. The researchers determined that the time-weighted average student exposure to fine particle pollutants was reduced by more than half when the dorm air was being purified, though average student exposure was estimated at 24 mcg per cubic meter at best. The World Health Organization considers levels below 10 mcg to be safe.
Students in untreated dorms had significant increases in cortisol, cortisone, epinephrine, norepinephrine, and biomarkers of oxidative stress at 9 days compared to those in treated ones. Glucose, insulin, measures of insulin resistance, amino acids, fatty acids, and lipids differed significantly between treatment assignments, and the untreated dorm groups also saw 2.61% higher systolic blood pressure (95% confidence interval [CI], 0.39-4.79).
Glucocorticoids are known to affect blood pressure, the investigators noted. Serum cortisol and cortisone levels were 1.3 and 1.2 times higher for the students in the sham-treated dorms, with each 10-mcg increase in pollutant exposure associated with a 7.8% increase in cortisol (95% CI, 4.75-10.91) and a nearly 3.8% increase in cortisone (95% CI, 1.84-5.71). Similar exposure-dependent increases were seen for norepinephrine, melatonin, phenylalanine, tyrosine, L-tryptophan and other compounds.
“To the best of our knowledge, this is the first study that used the untargeted metabolomics approach to investigate human global metabolic changes in relation to changes in ambient [air pollution] exposures,” the investigators wrote in their analysis, adding that the findings “provide insights into the potential mechanisms of the adverse health effects that have been found to be associated with [pollution] exposure.”
Mr. Li and Dr. Cai recommended the use of indoor air purification technology as a practical way to reduce harmful exposure, noting that the benefits of long-term use, particularly relating to cardiovascular and metabolic health, remain to be established.
The study was funded with grants from national and regional government agencies in China, and none of its authors declared conflicts of interest.
Although the past decade has seen much advancement in our knowledge of how air pollutants promote cardiovascular diseases, important questions remain.
There is a need to better understand the precise nature and systemic pathways whereby ambient air pollution elicits a multitude of adverse responses in the heart and vasculature anatomically remote from the site of inhalation. Also, what can (and should) an individual do to protect oneself against the hazards of air pollution, given that substantial improvements in air quality throughout many parts of the world are likely decades away?
Li and colleagues have provided some significant insights into both of these issues. Responses to short-term exposure to high levels of pollution include increased blood pressure and insulin resistance, along with alterations in a battery of circulating markers indicative of systemic inflammation, oxidative stress, and platelet activation.
A distinguishing feature of their work is the detailed exploration of health responses using state-of-the-art metabolomic profiling. Although similar outcomes after brief exposure to ozone have been shown, this was the first usage of an untargeted metabolomic approach to evaluate the impact of ambient air pollution. The results confirm and extend the growing body of evidence that air pollution elicits systemic perturbations favoring the development of the metabolic syndrome. The findings also add to the growing body of evidence that simple interventions such as air purifier systems with high-efficiency filters can help protect against adverse health impacts of air pollution. The reduction in estimated exposure afforded by filtration favorably influenced most of the health outcomes (blood pressure, insulin resistance, oxidative stress, inflammation), curtailed pollution-induced activation of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, and helped mitigate the ensuing metabolomic perturbations.
Robert D Brook, MD, of the University of Michigan in Ann Arbor, and Sanjay Rajagopalan, MD, of Cleveland Hospitals, made these comments in an editorial (Circulation. 2017 Aug 14;136:628-31). Dr. Brook receives research support from RB, Inc. Dr. Rajagopalan had no disclosures.
Although the past decade has seen much advancement in our knowledge of how air pollutants promote cardiovascular diseases, important questions remain.
There is a need to better understand the precise nature and systemic pathways whereby ambient air pollution elicits a multitude of adverse responses in the heart and vasculature anatomically remote from the site of inhalation. Also, what can (and should) an individual do to protect oneself against the hazards of air pollution, given that substantial improvements in air quality throughout many parts of the world are likely decades away?
Li and colleagues have provided some significant insights into both of these issues. Responses to short-term exposure to high levels of pollution include increased blood pressure and insulin resistance, along with alterations in a battery of circulating markers indicative of systemic inflammation, oxidative stress, and platelet activation.
A distinguishing feature of their work is the detailed exploration of health responses using state-of-the-art metabolomic profiling. Although similar outcomes after brief exposure to ozone have been shown, this was the first usage of an untargeted metabolomic approach to evaluate the impact of ambient air pollution. The results confirm and extend the growing body of evidence that air pollution elicits systemic perturbations favoring the development of the metabolic syndrome. The findings also add to the growing body of evidence that simple interventions such as air purifier systems with high-efficiency filters can help protect against adverse health impacts of air pollution. The reduction in estimated exposure afforded by filtration favorably influenced most of the health outcomes (blood pressure, insulin resistance, oxidative stress, inflammation), curtailed pollution-induced activation of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, and helped mitigate the ensuing metabolomic perturbations.
Robert D Brook, MD, of the University of Michigan in Ann Arbor, and Sanjay Rajagopalan, MD, of Cleveland Hospitals, made these comments in an editorial (Circulation. 2017 Aug 14;136:628-31). Dr. Brook receives research support from RB, Inc. Dr. Rajagopalan had no disclosures.
Although the past decade has seen much advancement in our knowledge of how air pollutants promote cardiovascular diseases, important questions remain.
There is a need to better understand the precise nature and systemic pathways whereby ambient air pollution elicits a multitude of adverse responses in the heart and vasculature anatomically remote from the site of inhalation. Also, what can (and should) an individual do to protect oneself against the hazards of air pollution, given that substantial improvements in air quality throughout many parts of the world are likely decades away?
Li and colleagues have provided some significant insights into both of these issues. Responses to short-term exposure to high levels of pollution include increased blood pressure and insulin resistance, along with alterations in a battery of circulating markers indicative of systemic inflammation, oxidative stress, and platelet activation.
A distinguishing feature of their work is the detailed exploration of health responses using state-of-the-art metabolomic profiling. Although similar outcomes after brief exposure to ozone have been shown, this was the first usage of an untargeted metabolomic approach to evaluate the impact of ambient air pollution. The results confirm and extend the growing body of evidence that air pollution elicits systemic perturbations favoring the development of the metabolic syndrome. The findings also add to the growing body of evidence that simple interventions such as air purifier systems with high-efficiency filters can help protect against adverse health impacts of air pollution. The reduction in estimated exposure afforded by filtration favorably influenced most of the health outcomes (blood pressure, insulin resistance, oxidative stress, inflammation), curtailed pollution-induced activation of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, and helped mitigate the ensuing metabolomic perturbations.
Robert D Brook, MD, of the University of Michigan in Ann Arbor, and Sanjay Rajagopalan, MD, of Cleveland Hospitals, made these comments in an editorial (Circulation. 2017 Aug 14;136:628-31). Dr. Brook receives research support from RB, Inc. Dr. Rajagopalan had no disclosures.
Increases in stress hormone levels and other adverse metabolic changes accompany higher exposure to air pollution, Chinese researchers have found, while cutting indoor pollution levels appears to mitigate these effects.
Air pollution has been linked in epidemiological studies to increased risk of cardiovascular and metabolic diseases, but the mechanisms remain poorly understood. The new findings, published online Aug. 14 in Circulation, offer compelling evidence that air pollution may impact the central nervous system, and the hypothalamus-pituitary-adrenal axis especially (Circulation 2017 Aug 14;136:618-27).
The study design required that students spend as much time in their dorms as possible with the windows closed, though they could venture out for classes and exams. Fine particle concentration in the dorms treated by purifiers was 8.6 mcg per cubic meter during the study period, compared with a mean 101.4 outdoors. The researchers determined that the time-weighted average student exposure to fine particle pollutants was reduced by more than half when the dorm air was being purified, though average student exposure was estimated at 24 mcg per cubic meter at best. The World Health Organization considers levels below 10 mcg to be safe.
Students in untreated dorms had significant increases in cortisol, cortisone, epinephrine, norepinephrine, and biomarkers of oxidative stress at 9 days compared to those in treated ones. Glucose, insulin, measures of insulin resistance, amino acids, fatty acids, and lipids differed significantly between treatment assignments, and the untreated dorm groups also saw 2.61% higher systolic blood pressure (95% confidence interval [CI], 0.39-4.79).
Glucocorticoids are known to affect blood pressure, the investigators noted. Serum cortisol and cortisone levels were 1.3 and 1.2 times higher for the students in the sham-treated dorms, with each 10-mcg increase in pollutant exposure associated with a 7.8% increase in cortisol (95% CI, 4.75-10.91) and a nearly 3.8% increase in cortisone (95% CI, 1.84-5.71). Similar exposure-dependent increases were seen for norepinephrine, melatonin, phenylalanine, tyrosine, L-tryptophan and other compounds.
“To the best of our knowledge, this is the first study that used the untargeted metabolomics approach to investigate human global metabolic changes in relation to changes in ambient [air pollution] exposures,” the investigators wrote in their analysis, adding that the findings “provide insights into the potential mechanisms of the adverse health effects that have been found to be associated with [pollution] exposure.”
Mr. Li and Dr. Cai recommended the use of indoor air purification technology as a practical way to reduce harmful exposure, noting that the benefits of long-term use, particularly relating to cardiovascular and metabolic health, remain to be established.
The study was funded with grants from national and regional government agencies in China, and none of its authors declared conflicts of interest.
Increases in stress hormone levels and other adverse metabolic changes accompany higher exposure to air pollution, Chinese researchers have found, while cutting indoor pollution levels appears to mitigate these effects.
Air pollution has been linked in epidemiological studies to increased risk of cardiovascular and metabolic diseases, but the mechanisms remain poorly understood. The new findings, published online Aug. 14 in Circulation, offer compelling evidence that air pollution may impact the central nervous system, and the hypothalamus-pituitary-adrenal axis especially (Circulation 2017 Aug 14;136:618-27).
The study design required that students spend as much time in their dorms as possible with the windows closed, though they could venture out for classes and exams. Fine particle concentration in the dorms treated by purifiers was 8.6 mcg per cubic meter during the study period, compared with a mean 101.4 outdoors. The researchers determined that the time-weighted average student exposure to fine particle pollutants was reduced by more than half when the dorm air was being purified, though average student exposure was estimated at 24 mcg per cubic meter at best. The World Health Organization considers levels below 10 mcg to be safe.
Students in untreated dorms had significant increases in cortisol, cortisone, epinephrine, norepinephrine, and biomarkers of oxidative stress at 9 days compared to those in treated ones. Glucose, insulin, measures of insulin resistance, amino acids, fatty acids, and lipids differed significantly between treatment assignments, and the untreated dorm groups also saw 2.61% higher systolic blood pressure (95% confidence interval [CI], 0.39-4.79).
Glucocorticoids are known to affect blood pressure, the investigators noted. Serum cortisol and cortisone levels were 1.3 and 1.2 times higher for the students in the sham-treated dorms, with each 10-mcg increase in pollutant exposure associated with a 7.8% increase in cortisol (95% CI, 4.75-10.91) and a nearly 3.8% increase in cortisone (95% CI, 1.84-5.71). Similar exposure-dependent increases were seen for norepinephrine, melatonin, phenylalanine, tyrosine, L-tryptophan and other compounds.
“To the best of our knowledge, this is the first study that used the untargeted metabolomics approach to investigate human global metabolic changes in relation to changes in ambient [air pollution] exposures,” the investigators wrote in their analysis, adding that the findings “provide insights into the potential mechanisms of the adverse health effects that have been found to be associated with [pollution] exposure.”
Mr. Li and Dr. Cai recommended the use of indoor air purification technology as a practical way to reduce harmful exposure, noting that the benefits of long-term use, particularly relating to cardiovascular and metabolic health, remain to be established.
The study was funded with grants from national and regional government agencies in China, and none of its authors declared conflicts of interest.
FROM CIRCULATION
Key clinical point: Air pollution exposure is associated with increases in stress hormones and a wide array of other biochemical changes.
Major finding: Increases in pollution exposure corresponded to increases in cortisol, cortisone, epinephrine, and norepinephrine.
Data source: A randomized, double-blinded crossover trial on 55 subjects in Shanghai, China.
Disclosures: Chinese national and regional governments supported the study, whose authors declared no conflicts of interest.