Toxicants and Asthma – Recognizing Health Advocates and Champions for Asthmatics Everywhere

Toxicants and Asthma – Recognizing Health Advocates and Champions for Asthmatics Everywhere

“Polycyclic aromatic hydrocarbons, or PAHs — Exposure can come from breathing car exhaust, fossil fuel combustion, cigarette smoke, and wood smoke, among other routes. The toxicants were linked to problems such as reduced birth weight, asthma, and lower IQ.” Frederica Perera, Ph.D., Renowned environmental health scientist.

On behalf of the Asthma community around the globe, the World Asthma Foundation (WAF) salutes Frederica Perera as she is being honored for pioneering research, community engagement.

The NIEHS Spirit Lecture Awardee collaborates with disadvantaged groups to study how chemicals affect children and other vulnerable people.

Renowned environmental health scientist Frederica Perera, Ph.D., delivered the 2020 NIEHS Spirit Lecture on Mar. 5. Her talk was titled “Translational Research to Prevent Environmental Threats to Children: From Chemicals to Climate Change.”

Frederica Perera, Ph.D. stands at podium “NIEHS has been the main, visionary funder of our work on children’s environmental health. It’s so important to our field to have this enlightened support,” said Perera. (Photo courtesy of Steve McCaw)

Perera is a Columbia University professor and the founding director of the school’s Center for Children’s Environmental Health, which is co-funded by NIEHS. Her work focuses on pregnant women, children, and minority groups, who can be especially vulnerable to pollution.

“She is internationally recognized as a pioneer in the field of molecular epidemiology as it relates to better understanding how problems in the environment can lead to adverse health effects and disease,” said NIEHS Acting Director Rick Woychik, Ph.D.
Early-life vulnerability

In the late 1970s, after learning about an environmental disaster in Minamata Bay, Japan, Perera became inspired to pursue a scientific career in environmental health.
Rick Woychik, Ph.D. smiles at the audience from the podium “Dr. Perera has been a prolific author, with over 330 publications,” noted Woychik. (Photo courtesy of Steve McCaw)

“Women there had been eating fish that were very polluted by mercury from industrial sources,” she told the audience. “The women were fine, but their children had serious cerebral palsy-like symptoms and intellectual disorders.”

“There are 82 billion neurons in the average brain, but almost all were formed before we were born,” she said. “You can imagine how highly choreographed and complex this development is over a short time window, and how readily any external exposure — whether a physical toxicant or psychosocial stressor — could disrupt these processes.”
Frederica Perera, Ph.D. speaks to a large audience A packed audience listened closely to Perera’s lecture. (Photo courtesy of Steve McCaw)
Health effects over time

At Columbia, Perera and her colleagues seek to understand how early-life chemical exposures affect children’s health and brain development, and they look for potential long-term problems. The scientists follow cohorts of mother-child pairs in New York City (NYC), Poland, and China, tracking health effects of various substances over time.

In NYC, participants come from low-income African-American and Dominican households. Some findings from that cohort include the following.

Chlorpyrifos — Prenatal exposure to this insecticide was associated with lower birth weight, memory problems, and Parkinson’s Disease-like changes.
Phthalates — Found in cosmetics and plastic packaging, these chemicals were linked to reduced IQ in children who had been exposed to high concentrations prenatally.
Polybrominated diphenyl ethers, or PBDEs — These flame retardants were linked to reduced IQ in children who had high concentrations at birth.
Polycyclic aromatic hydrocarbons, or PAHs — Exposure can come from breathing car exhaust, fossil fuel combustion, cigarette smoke, and wood smoke, among other routes. The toxicants were linked to problems such as reduced birth weight, asthma, and lower IQ.

Many factors at play

According to Perera, understanding the effects of such exposures often is complicated by other factors, including genetics, nutrition, socioeconomic status, and climate change. She said that despite that complexity, studying individual chemicals still is beneficial.

“Most diseases require a set of sufficient causes,” Perera explained. “If we can take one of those causes out, it would be possible to prevent a child from developing a disease. Environmental exposures, by their very nature, are preventable once we identify them as harmful.”

Perera said that lowering the risks of environmental exposures will require a mix of regulatory policies, market reforms, and better data on the health and economic benefits of pollution mitigation.
Special award

“It’s a real honor for me to have the privilege to introduce Dr. Perera as this year’s recipient of the NIEHS Spirit Lecture Award,” said Woychik.

Angela King-Herbert, D.V.M. stands by Frederica Perera, Ph.D. holding an award Angela King-Herbert, D.V.M., Spirit Lecture Committee member and head of the National Toxicology Program Laboratory Animal Medicine Group, presented the award to Perera. (Photo courtesy of Steve McCaw)

The award recognizes outstanding women who balance their careers with public engagement, volunteering, and mentorship.

“She works with many different community groups to address the safety and health of children,” he said. “Dr. Perera is a fabulous communicator and is doing cutting-edge, exciting research.”

(Payel Sil, Ph.D., is an Intramural Research Training Award fellow in the NIEHS Inflammation and Autoimmunity Group.)

Study assesses asthma treatment options in African American children and adults

Use of long-acting bronchodilators had no impact for some African American children.

A new study of African Americans with poorly controlled asthma, found differences in patients’ responses to commonly used treatments. Contrary to what researchers had expected, almost half of young children in the study responded differently than older children and adults, and than white children in prior studies.

“We shouldn’t assume that current treatment strategies for asthma are ideal for all African Americans since for many years that population was not adequately represented in research,” said Elliot Israel, M.D., senior study author and director of clinical research in the Pulmonary and Critical Care Medicine Division at Brigham and Women’s Hospital. “We found that almost half of the African American children studied responded better to increasing the dose of inhaled corticosteroids than adding a long-acting bronchodilator. Thus, adding a long-acting bronchodilator may not be the right answer for nearly half of African American children.”

The National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, funded this research to assess the best approach to asthma management in African Americans, who suffer much higher rates of serious asthma attacks, hospitalizations, and asthma-related deaths than whites. The findings appear today in the New England Journal of Medicine.

The researchers examined how to escalate or “step-up” asthma treatments for African Americans whose asthma had not been treated adequately with low doses of inhaled corticosteroids, the standard starting treatment. The treatment choices in the trial included increasing the dose of inhaled steroid, adding a long-lasting bronchodilator (used to help open airways), or both.

Based on prior studies, investigators expected that increasing the inhaled corticosteroid dose would lead to improvement in most African American children needing treatment for asthma.

The researchers found that in children under 12 years of age, either approach was effective: nearly half (46%) responded better to increasing the inhaled corticosteroid dose alone and just as many (46%) responded better to increasing the inhaled corticosteroid dose and adding a long-lasting bronchodilator.

“This study suggests that we cannot look at results from one population and extrapolate the findings to African Americans or any other group,” said Michael Wechsler, M.D., principal investigator for the NHLBI-funded Best African American Response to Asthma Drugs (BARD) study and professor of medicine at National Jewish Health in Denver. “If children do not respond to one treatment, parents and providers could consider another option because there is almost a 50% chance of having a better response.”

The multicenter study included 574 participants — about half of whom were ages 5–11 and half 12 years and older. All participants in this study had at least one self-identified African American grandparent, with an average of approximately 80% African ancestry, based on genetic testing.

Of the adolescents over 11 years old and adults, most (49%) responded better to adding a long-lasting bronchodilator than to increasing the inhaled corticosteroid dose, though 20–25% in this group showed no difference in their responses to these approaches.

Investigators also examined whether patient characteristics, including genetic ancestry, could be used to predict the response to the “step-up” treatments in the study participants. But they were unable to use genes indicative of African ancestry, or any of the other patient characteristics they measured in this group of patients, to predict treatment response.

“Although we cannot attribute the study’s findings to genetic markers of African ancestry, there could be as-yet unknown genetic variants specific to people of African descent that affect how severe a patient’s asthma is,” said Wechsler.

Before the trial began, the researchers did not expect the participants to have a better response to treatment regimens that included long-lasting bronchodilators, despite the inclusion of these agents in treatment recommendations. They said they were surprised that many (46% of the young children and 49% of the older children and adults) improved with long-lasting bronchodilators.

“These results provide new data about the management of asthma patients who self-identify as African American regardless of genetic ancestry,” said James Kiley, Ph.D., director of the Division of Lung Diseases at NHLBI. “Every person and their provider should explore all of their management choices to achieve maximum asthma control, based on their response to specific medications.”

About the National Heart, Lung, and Blood Institute (NHLBI): NHLBI is the global leader in conducting and supporting research in heart, lung, and blood diseases and sleep disorders that advances scientific knowledge, improves public health, and saves lives. For more information, visit https://www.nhlbi.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Protein found in patients with severe asthma can help identify who would benefit from targeted drugs

Novel study establishes that airways periostin is the expression of type 2 endotype severe asthma and helps identify which patients may benefit from newly developed treatments and improved quality of life, report researchers in the journal CHEST®

Glenview, IL, October 22, 2018 – In a novel study, researchers succeeded in identifying patients with a form of severe asthma (type 2 endotype) by measuring periostin concentrations in their airways. These patients with the type 2 (T2) endotype may benefit from newly developed targeted treatments that have the potential to transform their quality of life, report researchers in the journal CHEST®.

Asthma can range from very mild with little or no need for medical treatment to severe and life-threatening. Severe asthma is clinically and biologically varied and identifying the specific type of asthma is crucial in targeting patients who will benefit from new treatment options. The role of periostin, a matricellular protein, in asthma and type 2 inflammatory responses, is an area of active research.

“The T2 immunity severe asthma endotype is one of the most consistent endotypes to emerge probably because it is a key driver in nearly half of all patients with asthma,” explained Giovanna E. Carpagnano, MD, PhD, Institute of Respiratory Diseases, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.

Investigators analyzed periostin concentrations in the airways of severely asthmatic subjects, evaluating the role of periostin in clustering the T2 endotype. They enrolled 40 consecutive severe asthmatic patients (25 asthmatics of T2 and 15 of non-T2 endotype); 21 patients with mild to moderate asthma; and 15 healthy control subjects. All individuals underwent exhaled breath condensate and sputum collection, eosinophil count in blood, fractional 32 exhaled nitric oxide (FeNO) and immunoglobulin E (IgE) measurement. They found that periostin is measurable in the airways and increased in severe asthmatic subjects, especially in those with the T2 endotype.

“There have been several studies about the value of periostin as a marker of severe eosinophilic asthma, but to measure it in blood limits its value as serum periostin derives from several sources outside the lung and can’t be considered an organ-specific marker,” noted Maria Pia Foschino Barbaro, MD, Institute of Respiratory Diseases, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy, who heads the group where the research was conducted.

“Unlike serum periostin, airways periostin is a useful marker of severe eosinophilic asthma and may help to phenotype patients that will respond to the biologic agents,” stated senior investigator Peter J. Barnes, MD, DSc, FCCP, of the Airway Disease Section, National Heart and Lung Institute, Imperial College London, UK. “The newly developed biological treatments have the potential to transform the quality of life of patients with T2 severe asthma. This study suggests that airways periostin is the expression of T2 severe asthma and if validated, could be a useful biomarker to apply stratified medicine for severe asthma, and could transform the quality of life of these patients.”

“Severe uncontrolled asthma is an expensive disease that accounts for more than 60 percent of the costs associated with the disease,” commented Prof. Carpagnano. “The newly developed biological treatments are expensive too, but if directed to the right patients, they will significantly reduce the global cost related to the management of severe asthmatic patients.”

Credit: CHEST®

Minority Children Failed By Asthma Inhalers: Genomic Analysis Reveals Why

UCSF Highlights Need for More Precision Medicine Research in Underserved Populations

University of California San Francisco researchers report that the largest-ever whole-genome sequencing study of drug response in minority children has revealed new clues about why the front-line asthma drug albuterol does not work as well for African-American and Puerto Rican children as it does for European American or Mexican children.

Asthma is the most common chronic childhood disease in the world, according to World Health Organization estimates. Children with asthma experience difficulty breathing as a result of chronic inflammation of the airways. This inflammation can be alleviated by inhaling drugs called bronchodilators that make the muscles lining the airways relax, allowing them to reopen.

Albuterol is the most commonly prescribed bronchodilator in the world, and often the only medication available to minority children in lower income settings.

Minority Children Respond Least

However, albuterol and other inhaler drugs do not work equally well for all children. In the U.S., Puerto Rican and African-American children – who also have the highest prevalence of asthma nationwide – respond least well to these life-saving drugs.

This may contribute to the four- to fivefold higher rate of death from asthma among these groups, compared to European Americans and Mexicans. Read more of the complete report at UCSF website.

What Researchers Said

“Despite the much higher impact of asthma among African-American and Puerto Rican populations, over 95 percent of studies of lung disease have been performed on people of European descent,” Angel Mak, PhD said. Mak is the UCSF Asthma Collaboratory’s director of genetic research. He was one of the lead authors on the team’s newest study, published in an early online version on March 6, 2018 in the pulmonology journal, American Journal of Respiratory and Critical Care Medicine.

The lab conducted the first large-scale whole genome sequencing study of asthma drug response in African Americans and Latinos. The researchers’ aim was to discover the genetic factors contributing to reduced albuterol response more than was possible in previous association studies.

The test group were a diverse lineup of 1,441 children with asthma who had either very high or very low response to the drug. The genome sequencing was provided courtesy of Trans-Omics for Precision Medicine (TOPMed) Program of the National, Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health.

Asthma Flare-ups in Children

Short-term increases in inhaled steroid doses do not prevent asthma flare-ups in children

NIH-funded findings challenge common practice of increasing doses at early signs of worsening symptoms.

Researchers have found that temporarily increasing the dosage of inhaled steroids when asthma symptoms begin to worsen does not effectively prevent severe flare-ups, and may be associated with slowing a child’s growth, challenging a common medical practice involving children with mild-to-moderate asthma.

The study, funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, will appear online on March 3 in the New England Journal of Medicine (NEJM) to coincide with its presentation at a meeting of the 2018 Joint Congress of the American Academy of Allergy, Asthma & Immunology (AAAAI) and the World Allergy Organization (WAO) in Orlando, Florida. It will appear in print on March 8th.

Asthma flare-ups in children are common and costly, and to prevent them, many health professionals recommend increasing the doses of inhaled steroids from low to high at early signs of symptoms, such as coughing, wheezing, and shortness of breath. Until now, researchers had not rigorously tested the safety and efficacy of this strategy in children with mild-to-moderate asthma.

“These findings suggest that a short-term increase to high-dose inhaled steroids should not be routinely included in asthma treatment plans for children with mild-moderate asthma who are regularly using low-dose inhaled corticosteroids,” said study leader Daniel Jackson, M.D., associate professor of pediatrics at the University of Wisconsin School of Medicine and Public Health, Madison, and an expert on childhood asthma. “Low-dose inhaled steroids remain the cornerstone of daily treatment in affected children.”

The research team studied 254 children 5 to 11 years of age with mild-to-moderate asthma for nearly a year. All the children were treated with low-dose inhaled corticosteroids (two puffs from an inhaler twice daily). At the earliest signs of asthma flare-up, which some children experienced multiple times throughout the year, the researchers continued giving low-dose inhaled steroids to half of the children and increased to high-dose inhaled steroids (five times the standard dose) in the other half, twice daily for seven days during each episode.

Though the children in the high-dose group had 14 percent more exposure to inhaled steroids than the low-dose group, they did not experience fewer severe flare-ups. The number of asthma symptoms, the length of time until the first severe flare-up, and the use of albuterol (a drug used as a rescue medication for asthma symptoms) were similar between the two groups.

Unexpectedly, the investigators found that the rate of growth of children in the short-term high-dose strategy group was about 0.23 centimeters per year less than the rate for children in the low-dose strategy group, even though the high-dose treatments were given only about two weeks per year on average. While the growth difference was small, the finding echoes previous studies showing that children who take inhaled corticosteroids for asthma may experience a small negative impact on their growth rate. More frequent or prolonged high-dose steroid use in children might increase this adverse effect, the researchers caution.

The study did not include children with asthma who do not take inhaled steroids regularly, nor did it include adults.

“This study allows caregivers to make informed decisions about how to treat their young patients with asthma,” said James Kiley, Ph.D., director of the NHLBI’s Division of Lung Diseases. “Trials like this can be used in the development of treatment guidelines for children with asthma.”

This work was supported by the following NHLBI grants: HL098102, HL098075, HL098090, HL098177, HL098098, HL098107, HL098112, HL098103, HL098115, HL098096. The NHLBI-funded study, Step Up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations (STICS) (NCT02066129), is part of the NHLBI AsthmaNet program, a nationwide clinical research network that explores new approaches in treating asthma from childhood to adulthood.

Part of the National Institutes of Health, the National Heart, Lung, and Blood Institute (NHLBI) plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The Institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics. NHLBI press releases and other materials are available online at https://www.nhlbi.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases.

Patient, Physician, and Health-System Factors Influencing the Quality of Antidepressant and Sedative Prescribing for Older, Community-Dwelling Adults.

Related Articles

Patient, Physician, and Health-System Factors Influencing the Quality of Antidepressant and Sedative Prescribing for Older, Community-Dwelling Adults.

Health Serv Res. 2016 Dec 26;:

Authors: Extavour RM, Perri M

Abstract
OBJECTIVE: To identify determinants of potentially inappropriate (PI) antidepressant and anxiolytic/sedative prescribing for older, community-dwelling adults.
DATA SOURCES/STUDY SETTING: Office visits from the 2010 National Ambulatory Medical Care Survey.
STUDY DESIGN: A cross-sectional study measuring associations between various patient and physician factors and prescribing of PI antidepressants, and PI sedatives among elderly, using Beers 2012/2015 criteria, a clinical decision model, and multivariate logistic regressions.
DATA COLLECTION: Visits by older adults (?65 years) involving medications were extracted to identify visits with antidepressants and sedatives.
PRINCIPAL FINDINGS: Black race, asthma, depression, osteoporosis, payment type, consultation time, and computer systems with prescribing support were associated with reduced odds of PI antidepressant prescribing among users. Income, chronic renal failure, diabetes, and obesity were associated with reduced odds of PI sedative prescribing. Female sex, white race, depression, increasing number of medications, and physician specialty were associated with increased odds of PI sedative prescribing.
CONCLUSIONS: Various patient and health-system factors influence the quality of antidepressant and sedative prescribing for older community-dwelling adults. Longer consultations and the use of computer systems with prescribing support may minimize potentially inappropriate antidepressant prescribing. As medication numbers increase, exposure to PI sedatives is more likely, requiring medication review and monitoring.

PMID: 28024315 [PubMed – as supplied by publisher]

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Ponciretin attenuates ethanol-induced gastric damage in mice by inhibiting inflammatory responses.

Related Articles

Ponciretin attenuates ethanol-induced gastric damage in mice by inhibiting inflammatory responses.

Int Immunopharmacol. 2016 Dec 22;43:179-186

Authors: Kang GD, Kim DH

Abstract
BACKGROUND: Poncirin (PO) and isosakuranetin (or ponciretin [PT]) are compounds found in fruits of the genus Citrus. They are frequently used in traditional Chinese medicine for the treatment of inflammation and asthma. Therefore, we examined their anti-gastritis effects in vitro and in vivo.
METHODS: The anti-inflammatory effects of PO and PT were examined using ethanol- or LPS-stimulated KATO III cells. Gastritis was induced in ICR mice via intragastric injection of absolute ethanol. Levels of inflammatory markers were measured by enzyme-linked immunosorbent assay, immunoblotting, and quantitative polymerase chain reaction.
RESULTS: Treatment with PT or PO inhibited the secretion of interleukin (IL)-8 and tumor necrosis factor (TNF) in ethanol- or LPS-stimulated KATO III cells. They also reduced the activation of nuclear factor kappa B (NF-?B). Pre-treatment with PT or PO significantly protected against ethanol-induced hemorrhagic gastritis, characterized by edema, tissue erosions, and mucosal friability in mice. Treatment with PT or PO suppressed ethanol-induced NF-?B activation and the release of TNF, IL-8, and IFN-?. The protective effect of PT was greater than that of PO and comparable to ranitidine, a positive control.
CONCLUSION: PT may attenuate ethanol-induced gastritis by inhibiting the infiltration of immune cells, including neutrophils, via the regulation of CXCL4 (or IL-8) secretion and the activation NF-?B.

PMID: 28013186 [PubMed – as supplied by publisher]

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Ventilation/perfusion ratio and right to left shunt in healthy newborn infants.

Related Articles

Ventilation/perfusion ratio and right to left shunt in healthy newborn infants.

J Clin Monit Comput. 2016 Dec 23;:

Authors: Dassios T, Ali K, Rossor T, Greenough A

Abstract
Oxygenation impairment can be assessed non-invasively by determining the degree of right-to-left shunt and ventilation/perfusion (VA/Q) inequality. These indices have been used in sick newborn infants, but normative values have not been reported which are essential to determine the magnitude of the abnormality. We, therefore, aimed to measure the shunt and VA/Q in infants with no history of respiratory conditions and determine if there was any effect of supine or prone position and the reproducibility of the data. Data were analysed from infants who had undergone a hypoxic challenge and in a subset who had been assessed in the supine or prone position. Transcutaneous oxygen saturations (SpO2) were recorded at fractions of inspired oxygen (FIO2) of 0.21 and 0.15. Two independent raters used a computer software algorithm which analysed and fitted paired data for FIO2 and SpO2 and derived a curve which represented the best fit for each infant’s data and calculated the shunt and VA/Q. The raters ability to interpret the SpO2 value which corresponded to a given FIO2 was compared. The downwards displacement of the FIO2 versus SpO2 curve was used to estimate the degree of right-to-left shunt and the rightwards shift of the curve was used to calculate the VA/Q ratio. The mean (SD) gestational age of the 145 infants was 39 (1.6) weeks, their birth weight was 2990 (578) gms and median (range) postnatal age at measurement 3 (1-8) days. The mean (SD) VA/Q ratio was 0.95 (0.21). None of the infants had a right-to-left shunt. No significant differences were found in VA/Q in the supine compared to the prone position. The intraclass correlation coefficient of VA/Q between two independent raters was 0.968 (95% CI 0.947-0.980), p?<?0.001. Right-to-left shunt and VA/Q ratio in healthy newborn infants were similar in the prone compared to the supine position.

PMID: 28012013 [PubMed – as supplied by publisher]

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Interventions To Help Asthma Clinical Adherence

Conditions:   Asthma/Drug Therapy;   Medication Adherence/Statistics & Numerical Data;   Reminder Systems;   Humans;   Hispanic Americans;   Communication Barriers;   Child
Interventions:   Device: SmartInhaler with reminder function turned on;   Device: SmartInhaler
Sponsors:   University of California, San Francisco;   Academic Pediatric Association
Not yet recruiting – verified December 2016

View full post on ClinicalTrials.gov: asthma | Studies received in the last 14 days