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Tag: Allergy

  • FDA approves omalizumab for food allergy reactions based on NIH research

    FDA approves omalizumab for food allergy reactions based on NIH research

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    Today’s Food and Drug Administration approval of a supplemental biologics license for the monoclonal antibody omalizumab (Xolair) highlights the vital role of the National Institutes of Health-supported research that underpins the FDA decision.

    FDA has approved omalizumab for the reduction of allergic reactions, including anaphylaxis, that may occur with an accidental exposure to one or more foods in adults and children aged 1 year and older with food allergy. People taking omalizumab still need to avoid exposure to foods to which they are allergic. Omalizumab previously received FDA approval for three other indications, including the treatment of moderate-to-severe persistent allergic asthma in certain patients.

    The new FDA approval is based on data from a planned interim analysis of a Phase 3 clinical trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH. The trial is called Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen OIT in Food Allergic Children and Adults, or OUtMATCH. Investigators in the NIAID-funded Consortium for Food Allergy Research conducted the trial.

    Detailed final results from the first stage of the trial will be presented at the American Academy of Allergy, Asthma & Immunology Annual Meeting in Washington, D.C. during a late-breaking symposium titled, “Omalizumab for the Treatment of Food Allergy: The OUtMATCH Study” on Sunday, Feb. 25, 2024, at 1:45 pm ET. An online supplement of the Journal of Allergy and Clinical Immunology published an abstract outlining the final results on Feb. 5, 2024. 

    NIAID funds the trial with additional support from and collaboration with Genentech, a member of the Roche Group, and Novartis Pharmaceuticals Corporation. The two companies collaborate to develop and promote omalizumab and are supplying it for the trial. 

    Additional information about the ongoing OUtMATCH trial is available at ClinicalTrials.gov under study identifier NCT03881696.

    Source:

    NIH/National Institute of Allergy and Infectious Diseases

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  • Maternal mRNA COVID-19 vaccination shields infants for six months

    Maternal mRNA COVID-19 vaccination shields infants for six months

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    Women who receive an mRNA-based COVID-19 vaccination or booster during pregnancy can provide their infants with strong protection against symptomatic COVID-19 infection for at least six months after birth, according to a study from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. These findings, published in Pediatrics, reinforce the importance of receiving both a COVID-19 vaccine and booster during pregnancy to ensure that infants are born with robust protection that lasts until they are old enough to be vaccinated.

    COVID-19 is especially dangerous for newborns and young infants, and even healthy infants are vulnerable to COVID-19 and are at risk for severe disease. No COVID-19 vaccines currently are available for infants under six months old. Earlier results from the Multisite Observational Maternal and Infant COVID-19 Vaccine (MOMI-Vax) study revealed that when pregnant volunteers received both doses of an mRNA COVID-19 vaccine, antibodies induced by the vaccine could be found in their newborns’ cord blood. This suggested that the infants likely had some protection against COVID-19 when they were still too young to receive a vaccine. However, researchers at the NIAID-funded Infectious Diseases Clinical Research Consortium (IDCRC), which conducted the study, did not know how long these antibody levels would last or how well the infants would actually be protected. The research team hoped to gather this information by following the infants through their first six months of life.

    In this portion of the study, researchers analyzed data from 475 infants born while their pregnant mothers were enrolled in the MOMI-Vax study. The study took place at nine sites across the United States. It included 271 infants whose mothers had received two doses of an mRNA COVID-19 vaccine during pregnancy. The remaining 204 infants in the study were born to mothers who had received both doses of an mRNA COVID-19 vaccine as well as a COVID-19 booster. To supplement data gathered during pregnancy and at birth, the infants were evaluated during at least one follow-up visit during their first six months after birth. Parents also reported whether their infants had become infected or had demonstrated COVID-19 symptoms.

    Based on blood samples from the infants, the researchers found that newborns with high antibody levels at birth also had greater protection from COVID-19 infection during their first six months. While infants of mothers who received two COVID-19 vaccine doses had a robust antibody response at birth, infants whose mothers had received an additional booster dose during pregnancy had both higher levels of antibodies at birth and greater protection from COVID-19 infection at their follow-up visits.

    While older children and adults should continue to follow guidance from the Centers for Disease Control and Prevention (CDC) to stay up-to-date on their COVID-19 vaccines and boosters, this study highlights how much maternal vaccination can benefit newborns too young to take advantage of the vaccine: During the course of this study, none of the infants examined required hospitalization for COVID-19. Researchers will continue to evaluate the data from the MOMI-Vax study for further insights concerning COVID-19 protection in infants.

    Source:

    NIH/National Institute of Allergy and Infectious Diseases

    Journal reference:

    Cardemil, C. V., et al. (2024). Maternal COVID-19 Vaccination and Prevention of Symptomatic Infection in Infants. Pediatrics. doi.org/10.1542/peds.2023-064252.

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  • Study finds gender disparity in quality of life for individuals with food allergies

    Study finds gender disparity in quality of life for individuals with food allergies

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    In a recent systematic review published in Clinical & Experimental Allergy, researchers examined the correlation between health-related quality of life (HRQL) and biological sex among individuals with immunoglobulin E (IgE)-related food allergies and their care providers.

    Study: Associations between gender and health-related quality of life in people with IgE-mediated food allergy and their caregivers: A systematic review. Image Credit: Kaspars Grinvalds/Shutterstock.com
    Study: Associations between gender and health-related quality of life in people with IgE-mediated food allergy and their caregivers: A systematic review. Image Credit: Kaspars Grinvalds/Shutterstock.com

    Background

    Food allergies have a significant impact on individuals and their caregivers, resulting in worse health-related quality of life (HRQL) due to tight dietary restrictions, a lack of treatment alternatives, and the fear of unintentional exposure. Previous studies have reported on the mental well-being and lifestyle implications of food allergy patients and their families but have considered only a subset of patient demographics, specifically gender.

    Understanding the characteristics that influence HRQL is critical for tailored food allergy care, yet there are discrepancies about the role of biological sex on HRQL outcomes among individuals with food allergies. Caregivers, particularly mothers, frequently carry the responsibility of managing food allergy-related anxiety, and mothers are over-represented in food allergy literature, which is most likely owing to gender differences in parenting.

    About the systematic review

    In the present systematic review, researchers examined gender-specific health-related quality of life (HRQL) measurements among food allergy patients, comparing them to those of parents and participants. They also investigated the influence of gender on allergen prevention and treatment.

    The team searched the Embase and Medline databases on April 4, 2022, updating them on December 5, 2023, including records from the APA PsycINFO database. The included studies were interventional or non-interventional studies published in English, reporting original research on the relationship between biological sex and health-associated life quality, as assessed using validated instruments, among individuals with immunoglobulin E-mediated food allergies.

    The team excluded studies evaluating HRQL among individuals with non-IgE-related food allergies and multiple allergies. They also excluded narrative reviews, case studies, gray literature, conference abstracts, opinion pieces, and systematic reviews. Study interventions included educational, medicinal, and psychological types. In cases of undocumented health-associated life quality scores for sex-stratified subgroups, the team extracted p-values denoting HRQL differences in females vs. males.

    Two researchers independently screened titles and abstracts before full-text review to confirm eligibility. The team used the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) to assess study quality and the ROBINS-E tool to conduct sensitivity analyses for non-interventional records. They evaluated bias risks using traffic light plots.

    Results

    Initially, the team identified 4,799 studies, of which 3,927 underwent title-abstract screening, 426 underwent full-text screening, and 34 studies (24 non-interventional and 10 interventional) were analyzed. Researchers used several HRQL instruments in the included studies, of which the age-specific Food Allergy Quality of Life Questionnaire (FAQLQ) was the most frequent, revealing sex-based differences in subdomains associated with emotional impact and dietary risk.

    Female participants with food allergies (63% of studies with pediatric participants, 83% of studies with adult participants) and the maternal parents of individuals with food allergies (50% of caregiver studies) reported poorer health-related quality of life than their male counterparts, irrespective of age, especially in emotional, physical, and food anxiety-associated wellness domains. The team observed sex-based disparities in child health-related quality of life following food allergen immunological therapy. However, selective documentation in the interventional studies indicated that the directional course of the association was unclear.

    Caregiver gender did not impact the proxy-documented health-related quality of life of the study participants, nor did the biological sex of the child affect the caregiver’s health-related quality of life. All studies, except one, received critical to serious bias risk ratings in ROBINS-I evaluations. The most frequent bias sources in the included studies were related to HRQL measurements due to investigators and study participants being aware of interventions and exposure statuses and through inconsistent or inadequate confounding factor considerations. Sensitivity analysis found slight differences in bias risk classifications of poorer quality in four studies of the non-interventional type, as assessed using the ROBINS-E tool, for insufficient consideration of primary bias sources.

    Conclusions

    Overall, the review findings highlighted the impact of gender on HRQL in IgE-related food allergies, with female adults and children reporting lower baseline overall HRQL and mothers experiencing lower subdomain HRQL. The findings emphasize the necessity for personalized allergy treatment techniques and stratifying HRQL outcomes by gender in allergen immunotherapy studies.

    In food allergy investigations, biological sex should be considered a factor influencing participant overall and domain-specific HRQL outcomes. Females with food allergies had lower baseline HRQL total scores than males, with comparable gender disparities across HRQL subdomains.

    The study reveals that an interaction between gender and allergen type may influence HRQL results following therapy. Future studies should concentrate on gender in HRQL to lessen reliance on subgroup and sensitivity analysis.

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  • Stapokibart shows promise in reducing nasal congestion in seasonal allergy patients, study finds

    Stapokibart shows promise in reducing nasal congestion in seasonal allergy patients, study finds

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    In a recent study published in EClinicalMedicine, researchers assessed the efficacy and safety of stapokibart as an add-on therapy in patients with moderate-to-severe uncontrolled seasonal allergic rhinitis (SAR).

    Study: Efficacy and safety of stapokibart (CM310) in uncontrolled seasonal allergic rhinitis (MERAK): an investigator-initiated, placebo-controlled, randomised, double-blind, phase 2 trial. Image Credit: wavebreakmedia/Shutterstock.comStudy: Efficacy and safety of stapokibart (CM310) in uncontrolled seasonal allergic rhinitis (MERAK): an investigator-initiated, placebo-controlled, randomised, double-blind, phase 2 trial. Image Credit: wavebreakmedia/Shutterstock.com

    Background 

    Allergic rhinitis (AR), affecting up to half the global population, is an Immunoglobulin E (IgE)-mediated inflammatory condition of the nasal mucosa, leading to symptoms like sneezing, congestion, and often ocular discomfort.

    It poses a significant socio-economic burden, with costs reaching €50 billion annually. AR divides into SAR and perennial forms, with SAR, triggered by outdoor pollen, showing higher inflammation and more severe symptoms.

    Despite treatments like antihistamines and corticosteroids, over 60% of SAR patients report inadequate symptom control. Biologics targeting type 2 inflammation, such as omalizumab, have shown benefits, yet their role in post-standard care remains unclear.

    Further research is needed to conclusively determine the effectiveness and safety of biological treatments in managing uncontrolled SAR and to optimize patient care strategies.

    About the study 

    In the present comprehensive phase 2 trial conducted across six sites in China, researchers embarked on a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of stapokibart in treating SAR.

    Participants, aged 18 to 65 with a documented history of SAR and insufficient response to conventional treatments, were randomized in a 1:1:1 ratio to receive stapokibart 300 mg either weekly or biweekly or a placebo, alongside mometasone furoate nasal spray and oral loratadine over a 4-week treatment period, followed by an 8-week follow-up.

    The study rigorously adhered to ethical standards, following the Declaration of Helsinki and Good Clinical Practice, with ethics committee approvals from each center.

    It strictly selected participants with confirmed SAR, significant pollen exposure, and considerable baseline symptoms. It used comprehensive assessments via the Rhinoconjunctivitis Quality-of-Life Questionnaire, including daily nasal and ocular symptom scores and life quality.

    It thoroughly analyzed efficacy and safety, focusing on nasal symptom changes over two weeks, alongside secondary evaluations of symptom variations, life quality, and treatment timings. Safety was closely monitored, including adverse events, lab tests, and vital signs.

    Statistical analyses were conducted with precision, aiming to demonstrate the superiority of stapokibart over placebo with adjusted type I error rates.

    A sample size calculation ensured adequate power to detect significant differences, accounting for potential dropouts.

    Efficacy endpoints were analyzed using an Analysis of Covariance (ANCOVA) model, with a rigorous plan for handling missing data and ensuring robust results. 

    Study results 

    Between August 17 and December 28, 2022, the present study screened 172 patients for SAR, enrolling 93 from four centers, with 92 receiving treatment. The participants, averaging 37 years old and mostly female, had SAR for an average of 7.6 years.

    Despite treatment, stapokibart did not significantly outperform placebo in reducing total nasal symptom scores (rTNSS) over two weeks.

    However, when administered biweekly, stapokibart showed notable improvement in nasal congestion and ocular symptoms, with significant reductions in both nasal and ocular symptom scores compared to placebo. 

    The study observed mild to moderate treatment-emergent adverse events, with a lower incidence in the stapokibart groups compared to placebo.

    Further exploratory analyses illuminated that biweekly stapokibart led to more days with mild or no symptoms, alongside a noteworthy decrease in inflammation markers.

    Especially notable was the discovery from subgroup analyses that individuals with higher initial eosinophil counts exhibited more pronounced benefits from the biweekly stapokibart regimen.

    Despite the primary outcomes not demonstrating significant differences, the study’s secondary and exploratory findings hint at stapokibart’s potential advantages, particularly for patients with elevated eosinophil levels.

    This insight propels the argument for additional research into stapokibart’s role in treating SAR, suggesting that its real value may lie in a more targeted application based on specific patient profiles.

    Conclusions 

    To summarize, the trial found that while stapokibart, administered either weekly or biweekly, did not significantly change total nasal symptom scores over placebo, it effectively improved nasal and ocular symptom scores in SAR patients, especially those with high eosinophil counts.

    It was the first to assess biologics as an add-on during pollen exposure for patients with uncontrolled SAR.

    Subgroup analysis revealed significant symptom improvements in patients with high eosinophil levels, aligning with stapokibart’s targeted inflammation mechanism.

    Despite a generally well-tolerated safety profile, no linear dose-response relationship was observed, highlighting the need for further research.

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  • Congressman off-base in ad claiming Fauci shipped covid to Montana before the pandemic

    Congressman off-base in ad claiming Fauci shipped covid to Montana before the pandemic

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    A fundraising ad for U.S. Rep. Matt Rosendale (R-Mont.) shows a photo of Anthony Fauci, former director of the National Institute of Allergy and Infectious Diseases, behind bars, swarmed by flying bats.

    Rosendale, who is eyeing a challenge to incumbent Sen. Jon Tester, a Democrat, maintains that a Montana biomedical research facility, Rocky Mountain Laboratories in Hamilton, has a dangerous link to the pandemic. This claim is echoed in the ad:

    “It’s been revealed that Fauci brought COVID to the Montana one year before COVID broke out in the U.S!,” it charges in all-caps before asking readers to “Donate today and hold the D.C. bureaucracy accountable!”

    The ad, paid for by Matt Rosendale for Montana, seeks contributions through WinRed, a platform that processes donations for Republican candidates. Rosendale also shared the fundraising pitch on his X account Nov. 1, and it remained live as of early February.

    Rosendale made similar accusations on social media, during a November speech on the U.S. House floor, and through his congressional office. Sometimes his comments, like those on the House floor, are milder, saying the researchers experimented on “a coronavirus” leading up to the pandemic. Other times, as in an interview with One America News Network, he linked the lab’s work to covid-19’s spread.

    In that interview clip, Rosendale recounted pandemic-era shutdowns before saying, “And now we’re finding out that the National Institute of Health, Rocky Mountain Lab, down in Hamilton, Montana, had also played a role in this.”

    Rosendale’s statements echo broader efforts to scrutinize how research into viruses happens in the United States and is part of a continued wave of backlash against scientists who have studied coronaviruses. Rosendale is considering seeking the Republican nomination to challenge Tester, in a toss-up race that could help determine which party controls the Senate in 2025. Political newcomer Tim Sheehy is also seeking the Republican nomination for the Senate.

    Rosendale proposed amendments to a health spending bill that would ban pandemic-related pathogen research funding for Rocky Mountain Laboratories and cut the salary of one of its top researchers, virologist Vincent Munster, to $1. The House has included both amendments in the Health and Human Services budget bill that the Republican majority hopes to pass. A temporary spending bill is funding the health department until March.

    We contacted Rosendale’s congressional office multiple times — with emails, a phone call, and an online request — asking what proof he had to back up his statements that the Montana lab infected bats with covid from China before the outbreak. We got no reply.

    Kathy Donbeck, of the National Institute of Allergy and Infectious Diseases’ Office of Communications and Government Relations, said in an email that the ad’s claims are false. Interviews with virologists and a review of the research paper published shortly before Rosendale’s assertions support that position.

    Where this is coming from

    Rosendale’s statements seem to stem from a Rocky Mountain Laboratories study from 2016 that looked into how a coronavirus, WIV1-CoV, acted in Egyptian fruit bats. The work, published by the journal Viruses in 2018, showed that the specific strain didn’t cause a robust infection in the bats.

    The study did not receive widespread attention at the time. But on Oct. 30, 2023, the study was highlighted by a blog called White Coat Waste Project, which says its mission is to stop taxpayer-funded experiments on animals. Some right-wing media outlets began to connect the Montana lab with the coronavirus that causes covid.

    Rosendale’s office issued an Oct. 31 news release saying the Wuhan Institute of Virology in China “shipped a strain of coronavirus” to the Hamilton lab. “Our government helped create the Wuhan flu, then shut the country down when it escaped from the lab,” Rosendale said.

    It’s a different virus

    Rocky Mountain Laboratories is a federally funded facility as part of NIAID, the nation’s top infectious disease research agency, which Fauci led for nearly 40 years.

    According to the study and Donbeck’s email, the Montana researchers focused on a coronavirus called WIV1-CoV, not the covid-causing SARS-CoV-2. They’re different viruses.

    “The genetics of the viruses are very different, and their behavior biologically is very different,” said Troy Sutton, a virologist with Pennsylvania State University who has studied the evolution of pandemic influenza viruses.

    In a review of media reports on the Montana study, Health Feedback, a network of scientists that fact-checks health and medical media coverage, showed the virus’s lineage indicated that WIV1 “is not a direct ancestor or even a close relative of SARS-CoV-2.”

    Additionally, the description of the coronavirus strain as being “shipped” suggests that it physically traveled across the world. That’s not what happened.

    The Wuhan Institute of Virology provided the WIV1 virus’s sequence that allowed researchers to make a lab-grown copy. A separate study, published in 2013 by the journal Nature, outlines the origins of the lab-created virus.

    According to the study’s methodology, the researchers used a clone of WIV1. An NIAID statement to Lee Enterprises, a media company, said the virus “was generated using common laboratory techniques, based on genetic information that was publicly shared by Chinese scientists.”

    Stanley Perlman, a University of Iowa professor who studies coronaviruses and serves on the federal advisory committee that reviews vaccines, said Rosendale’s claim is off-base.

    He said Rosendale’s focus on where the lab got its materials is irrelevant and serves “only to make people wary and scared.”

    Rosendale’s efforts to prohibit particular research at Rocky Mountain Laboratories appear ill-informed, too. Rosendale targeted banning gain-of-function research, which involves altering a pathogen to study its spread. In her email, NIAID’s Donbeck said the Rocky Mountain Laboratories study didn’t involve gain-of-function research.

    This type of research has long been controversial, and people who study viruses have said the definition of “gain of function” is problematic and insufficient to show when research, or even work to create vaccines, could cross into that type of research.

    But both Sutton and Perlman said that, any way you look at it, the Rocky Mountain Laboratories study published in 2018 didn’t change the virus. It put a virus in bats and showed it didn’t grow.

    And it had no effect on the covid outbreak a year later, first detected in Washington state.

    Our ruling

    Rosendale’s ad said, “It’s been revealed that Fauci brought COVID to the Montana one year before COVID broke out in the U.S!” The campaign ad and Rosendale’s similar statements refer to research at the Rocky Mountain Laboratories involving WIV1, a coronavirus that researchers say is not even distantly close in genetic structure to SARS-CoV-2, the virus that caused covid-19.

    Rosendale’s claim is wrong about when the scientists began their work, what they were studying, and where they got the materials. The researchers began their work in 2016 and, although they were studying a coronavirus, it wasn’t the virus that causes covid. The Montana scientists used a lab-grown clone of WIV1 for their research. The first laboratory-confirmed case of covid was not detected in the U.S. until Jan. 20, 2020. Rosendale’s ad is inaccurate and ridiculous. We rate it Pants on Fire!

    Sources:

    Viruses, “SARS-Like Coronavirus WIV1-CoV Does Not Replicate in Egyptian Fruit Bats (Rousettus aegyptiacus),” Dec. 19, 2018

    White Coat Waste Project, “Horror Show: Shady Zoo Sent Bats to NIH to Be Infected With a Wuhan Lab Coronavirus,” Oct. 30, 2023

    MattForMontana X post, Nov. 1, 2023

    Campaign ad, accessed Dec. 14, 2023

    Rep. Matt Rosendale, House floor speech, Nov. 14, 2023

    One America News Network, interview, accessed Dec. 14, 2023

    Rosendale congressional office, “Rep. Rosendale Reacts to Reports That Wuhan Lab Shipped Coronavirus to Fauci-Run Lab in Hamilton Prior to Pandemic,” Oct. 31, 2023

    National Institute of Allergy and Infectious Diseases, “History of Rocky Mountain Labs (RML),” accessed Dec. 14, 2023

    Email exchange with NIAID, beginning Dec. 14, 2023

    Statement from NIAID provided to Lee Enterprises, accessed Jan. 2, 2024

    Nature, “Isolation and Characterization of a Bat SARS-Like Coronavirus That Uses the ACE2 Receptor,” Oct. 30, 2013

    Ravalli Republic, “Rosendale Moves to Strip Rocky Mountain Lab Research Funding,” Nov. 17, 2023

    Interview, Troy Sutton, assistant professor of veterinary and biomedical sciences at Pennsylvania State University, Jan. 5, 2024

    Interview, Stanley Perlman, professor of microbiology and immunology and professor of pediatrics at the University of Iowa, Jan. 13, 2024

    FDA, “Roster of the Vaccines and Related Biological Products Advisory Committee,” accessed Jan. 16, 2024

    Health Feedback, “2018 Coronavirus Research in NIAID Montana Lab Is Unrelated to the COVID-19 Pandemic, Contrary to Claim by Fox News’s Jesse Watters,” last accessed Jan. 17, 2024

    Email exchange with OpenSecrets, an independent research group tracking money in politics, beginning Jan. 30, 2024

    CDC Museum COVID-19 Timeline, accessed Feb. 2, 2024




    Kaiser Health NewsThis article was reprinted from khn.org, a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.



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  • Study shows how low dose of cadmium produces deleterious stress in lung epithelial cells

    Study shows how low dose of cadmium produces deleterious stress in lung epithelial cells

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    Cigarette smoke exposure is associated with the development and severity of chronic obstructive pulmonary disease, or COPD, which is the third leading cause of death worldwide.

    Cigarette smoke contains 2 to 3 micrograms of cadmium, a highly toxic metal and environmental pollutant, per cigarette. Burning tobacco releases cadmium oxide that can be adsorbed onto microparticles in smoke that travel deep into the lungs. Furthermore, the body is not able to remove cadmium, which accumulates in longtime smokers.

    In a Scientific Reports study, University of Alabama at Birmingham researchers show how a low dose of cadmium produces a deleterious stress in lung epithelial cells, and their findings highlight potential therapeutic targets to be explored in cadmium-exposure and subsequent lung injury.

    The research, led by Veena Antony, M.D., a professor in the UAB Department of Medicine, focuses on microRNA-381, and the expression of a chloride channel gene called ANO1 in lung tissue samples and airway epithelial cells. ANO1 helps produce mucus in the airway; but overproduction of mucus in chronic lung disease can lead to airway thickening and mucus blockage, adding to severity of the disease. Thus, overexpression of ANO1 can exacerbate COPD.

    The UAB researchers compared lung tissue samples from nine “never” smokers, who had zero history of cigarette smoking, and lung tissue samples from 13 “ever” smokers with COPD who had a history of smoking that ranged from 15 to 25 pack years per person. One pack year is generally defined as smoking one pack of cigarettes a day for one year. The researchers found that “ever” smokers, in contrast to “never” smokers, had upregulated ANO1 expression in airway epithelial cells.

    Similarly, airway epithelial cells in a bronchoalveolar lavage fluid from one non-COPD subject and one smoker with COPD showed greater ANO1 expression in the COPD-subject cells.

    The researchers next tested the direct effect of very low doses of cadmium on normal human airway epithelial cells. These cells were grown on an air-liquid interface that allows the airway cells to differentiate normally. Two weeks of exposure to 0.5 or 1.0 micromolar cadmium chloride in the liquid layer increased expression of ANO1 12 to 14 times.

    MicroRNAs have the ability to downregulate expression of a gene by direct interaction with that gene’s mRNA sequence. The UAB team used computer software analysis to identify microRNA-381 as the microRNA with most interaction with ANO1 mRNAs, suggesting that microRNA-381 is a negative regulator of ANO1. Some heavy metals are known to negatively regulate microRNAs.

    Antony and colleagues used a synthetic inhibitor for microRNA-381 to inhibit the expression of microRNA-381 in primary human airway epithelial cells from subjects with COPD, and found that ANO1 expression was upregulated significantly. In contrast, adding a microRNA-381-mimic -; a synthetic RNA that acts like microRNA-381 to increase the amount of negative regulation -; to those cells decreased ANO1 expression. These results strengthened the premise of the UAB researchers that cadmium negatively regulates microRNA-381 expression to upregulate ANO1 expression in airway epithelial cells.

    Lastly, researchers found that, even when primary human airway epithelial cells from subjects with COPD were also exposed to 1 micromolar cadmium chloride, the microRNA-381 inhibitor still upregulated ANO1 and the mimic still downregulated ANO1.

    Our observations from experiments involving low-dose cadmium-exposure of epithelial cells suggest that ANO1 is a direct target for miR-381, which is downregulated upon low-dose cadmium exposure. Thus, cigarette-induced cadmium-toxicity may alter cellular homeostasis mechanisms at very low concentrations, and cadmium-exposure in a person with an existing pulmonary condition can have an additive or adverse effect with increased susceptibility toward infections and environmental allergens.


    This interaction of cadmium, microRNA-381 and ANO1 suggests that microRNAs may act as potential therapeutic targets to be explored further in cadmium-exposure and subsequent lung injury.”


    Veena Antony, M.D., Professor, UAB Department of Medicine

    At UAB, Antony holds the Endowed Professorship in Environmental Medicine, directs the Superfund Research Center, and is a member of the Division of Pulmonary, Allergy and Critical Care Medicine.

    Co-authors with Antony in the study, “Low dose cadmium exposure regulates miR‑381–ANO1 interaction in airway epithelial cells,” are Pooja Singh, Fu Jun Li, Kevin Dsouza, Crystal T. Stephens, Huaxiu Zheng and Mark T. Dransfield, UAB Department of Medicine Division of Pulmonary, Allergy and Critical Care Medicine; and Abhishek Kumar, UAB Superfund Center Advisory Board, Gainesville, Florida.

    Support came from National Institute of Environmental Health Sciences grant ES027723.

    Source:

    University of Alabama at Birmingham

    Journal reference:

    Singh, P., et al. (2024). Low dose cadmium exposure regulates miR-381–ANO1 interaction in airway epithelial cells. Scientific Reports. doi.org/10.1038/s41598-023-50471-z.

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  • IU surgeon-scientist investigates the role of sinus microbiome in chronic rhinosinusitis

    IU surgeon-scientist investigates the role of sinus microbiome in chronic rhinosinusitis

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    An Indiana University School of Medicine surgeon-scientist is leading a multi-institutional grant investigating the role of the sinus microbiome in chronic rhinosinusitis, an inflammatory disease that causes the lining of the sinuses to swell. The research team will study biospecimens from human sinus surgery patients in the lab and examine how bacteria in the microbiome shape the disease process and might offer novel therapeutic strategies.

    Vijay Ramakrishnan, MD, professor of otolaryngology-;head and neck surgery and a primary member of Stark Neurosciences Research Institute, has spent over a decade investigating the microbiome. The five-year, $2.9 million grant from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, is a first-of-its-kind grant studying the physiological effect of the sinus microbiome on chronic rhinosinusitis.

    The microbiome is an accumulation of microorganisms-;bacteria, fungi and viruses-;that live within areas of the human body, such as the gut and sinus cavities. These microbes can shape a person’s health, predispose people to disease, act as disease modifiers and influence how people respond to specific treatments. In chronic rhinosinusitis, scientists believe microbes and bacteria play a role in sinus inflammation beyond a person’s traditional sinus infection.

    The upper airway is heavily colonized with bacteria, and the different types of influence immune processes and the general function of the surface lining. If we can steer the microbiome into a favorable healthy state, there are some functions that we can influence to maybe get us better treatment results.”


    Vijay Ramakrishnan, MD, professor of otolaryngology-;head and neck surgery and a primary member of Stark Neurosciences Research Institute

    Ramakrishnan will work with researchers at the University of Colorado School of Medicine, led by Daniel Frank, PhD. Ramakrishnan started his research of the microbiome when he was a faculty member at the University of Colorado; he joined IU School of Medicine in January 2022.

    Chronic rhinosinusitis affects nearly 10% of adults in the United States. Most patients manage the disease medically through sinus rinses, nasal spray medications and allergy treatments. It’s estimated, however, that 15% of chronic rhinosinusitis patients pursue sinus surgery, where most cases result in subpar outcomes, Ramakrishnan said. The volume of chronic rhinosinusitis cases, he added, is expected to rise due to climate change, pollution and western diet.

    Antibiotics have long been prescribed for chronic rhinosinusitis-;it’s one of the top conditions for antibiotic use, according to the Centers for Disease Control and Prevention-;but they haven’t shown to be effective in treating most patients, Ramakrishnan said. The disease is now viewed as inflammatory rather than infectious, creating a need to develop new treatment strategies.

    “This problem is very prevalent in adults. There’s only a handful of therapies, and they work about 75% of the time,” Ramakrishnan said. “Understanding the role of microbiome in this disease and focusing clinical approaches to restrict antibiotic use are our two main health outcomes.”

    Researchers will collect biospecimens of surgical patients to investigate host-microbial processes in airway mucosal immunology. They’ll also use cell cultures to test how various microorganisms impact disease processes and initiate specific immune responses.

    The grant also supports a longitudinal multi-institutional human intervention study of chronic rhinosinusitis surgical patients. The research team will investigate patient outcomes, medication use and how the microbiome of patients changes over time, Ramakrishnan said.

    Ramakrishnan said this study moves beyond prior small observational studies by defining molecular, cellular, and immunological processes using a multi-omics approach, which incorporates data derived from transcriptomics and metabolomics.

    The team will collaborate with Thomas O’Connell, PhD, associate professor of otolaryngology-;head and neck surgery, to conduct tissue metabolomics and with IU network scientists at the Luddy School of Informatics, Computing, and Engineering at IU Bloomington to do a physics-based approach to understand networks of interaction between disease and patient outcomes and tissue-level multi-omics.

    “We’re trying to figure out which chronic rhinosinusitis patients have a microbial component that we can influence, to steer them to better outcomes and allow their own bodies to restore health, thereby limiting antibiotic use and number of interventions,” Ramakrishnan said.

    Source:

    Indiana University School of Medicine

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