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Tag: Respiratory Diseases and Disorders

  • FDA Approves “Glowing Tumor” Imaging Drug to Aid Lung Cancer Surgery

    FDA Approves “Glowing Tumor” Imaging Drug to Aid Lung Cancer Surgery

    Newswise — PHILADELPHIA—The U.S. Food and Drug Administration (FDA) has approved the targeted imaging agent Cytalux (pafolacianine) for use in lung cancer surgery. This injectable diagnostic binds to cancerous tissue and glows when stimulated by near-infrared light, making it easier for surgeons to remove tumors completely while sparing healthy tissue.

    Thoracic surgeons at the Center for Precision Surgery in the Abramson Cancer Center at the University of Pennsylvania led the clinical trials evaluating the imaging agent in lung cancer, in a partnership with the Indiana-based manufacturer, On Target Laboratories. This is the second approval for Cytalux, following an approval last year for ovarian cancer surgery, also based on clinical studies in which Penn Medicine led one of the largest sites in country.   

    “The availability of this imaging agent has major implications for thoracic surgery and lung cancer patients, who make up the vast majority of thoracic surgery cases,” said Sunil Singhal, MD, the William Maul Measey Professor in Surgical Research and director of the Center for Precision Surgery at Penn Medicine. “It will allow us to do less invasive operations, find additional cancer, and more accurately detect any remaining cancer, potentially saving patients from reoperation or additional therapy.”

    More than 130,000 Americans die of lung cancer each year, making lung cancer the leading cause of cancer mortality in the country. Lung cancer mortality is high largely because it tends to be diagnosed at later stages when the tumor has begun to spread. About 20 percent of cases, or roughly 50,000 per year, are localized enough to be treated surgically, in the hope of a cure. But even with surgery there is a high chance of recurrence, which implies that standard visual and tactile inspection often fails to detect all cancerous tissue.

    Cytalux was designed to enhance this detection rate in surgeries where the tumor is removed. The imaging drug is infused into the patient pre-operatively, and binds to a surface protein called the folate receptor alpha (FRα), which is expressed at abnormally high levels in lung tumors and several other types of tumor. The imaging agent is designed so that, under illumination with infrared light, it will produce a glowing emission that can be detected by a special infrared camera. The camera outputs to a real-time display, enhancing the surgeon’s ability to see probable cancerous tissue. This type of technology is known as intraoperative molecular imaging.

    The randomized Phase III ELUCIDATE trial (NCT04241315), completed last year, showed that the imaging agent helped detect cancer that would have been missed by conventional techniques in more than 50 percent of patients with confirmed or suspected lung cancer. Singhal was the principal investigator of the multi-site study and presented the results at the American Association for Thoracic Surgery Annual Meeting in May 2022.

    Penn Medicine has led the field of intraoperative imaging, driving advancements to bring this imaging agent to patients. As a pioneer in the field of tumor imaging, Singhal has been working with Cytalux for nearly a decade, spearheading efforts to study it in hundreds of surgeries, in both clinical trials and exploratory studies, for ovarian and lung cancer. The Center for Precision Surgery and its affiliated Penn Medicine researchers have also developed several other innovative technologies for imaging brain, breast, head and neck, and urinary tract cancers.

    “Today’s approval gives thoracic surgeons a new tool to accurately detect and remove cancer tissue, while sparing healthy lung tissue,” Singhal said. “With intraoperative molecular imaging, our ultimate goal is to improve patient care through more precise surgery.” 

    Editor’s Note: Funding for Cytalux clinical studies conducted at Penn and the Center for Precision Surgery was provided by On Target Laboratories.

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    Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $9.9 billion enterprise.

    The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according to U.S. News & World Report’s survey of research-oriented medical schools. The School is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $546 million awarded in the 2021 fiscal year.

    The University of Pennsylvania Health System’s patient care facilities include: the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center—which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report—Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

    Penn Medicine is powered by a talented and dedicated workforce of more than 52,000 people. The organization also has alliances with top community health systems across both Southeastern Pennsylvania and Southern New Jersey, creating more options for patients no matter where they live.

    Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2021, Penn Medicine provided more than $619 million to benefit our community.

    Perelman School of Medicine at the University of Pennsylvania

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  • Researchers ID Role of Enzyme as Regulator of Inflammation in Lung Disease

    Researchers ID Role of Enzyme as Regulator of Inflammation in Lung Disease

    Research Alert

    Article title: Pim-1 kinase is a positive feedback regulator of the senescent lung fibroblast inflammatory secretome

    Authors: Ashley Y. Gao, Ana M. Diaz Espinosa, Fiorenza Gianì, Tho X. Pham, Chase M. Carver, Aja Aravamudhan, Colleen M. Bartman, Giovanni Ligresti, Nunzia Caporarello, Marissa J. Schafer, Andrew J. Haak

    From the authors: “In conclusion, our findings demonstrate a critical role for Pim-1 kinase in regulating the inflammatory secretome of senescence lung fibroblasts and warrant further investigations into the utility of targeting Pim-1 as a therapy for [idiopathic pulmonary fibrosis].”

    This study is highlighted as one of December’s “best of the best” as part of the American Physiological Society’s APSselect program.


    Journal Link: American Journal of Physiology-Lung Cellular and Molecular Physiology

    American Physiological Society (APS)

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  • The body’s own cannabinoids widen the bronchial tubes

    The body’s own cannabinoids widen the bronchial tubes

    Newswise — Bronchial constriction is what makes many lung diseases like asthma so dangerous. Researchers have discovered a new signalling pathway that causes the airways to widen.

    Inhalation therapy for asthma and other obstructive lung diseases often loses its effect following prolonged use. A research team led by Professor Daniela Wenzel from the Department of Systems Physiology at Ruhr University Bochum, Germany, has now shown an alternative signalling pathway through which the body’s own cannabinoids cause the bronchial tubes to dilate. This gives rise to hope for alternative treatment options. Asthma is evidently also associated with a deficiency of these cannabinoids in the bronchial tubes, which could be one of the causes of the disease. The research team published its findings in the journal Nature Communications 17. November 2022.

    Bronchial tubes dilated by the body’s own cannabinoids

    Obstructive lung diseases are the third most common cause of death worldwide. They include chronic obstructive pulmonary disease (COPD), which affects many smokers, as well as bronchial asthma. During an asthma attack, the bronchial tubes contract so violently that it is no longer possible to exhale – and this can be life-threatening. “Asthma is an inflammatory process, but what is fatal is the constriction of the bronchial tubes,” explains Annika Simon, lead author of the study. “This is why we are very much interested in the regulation of this constriction.”

    In a previous study, the researchers had likewise focused on the body’s own cannabinoid system, specifically on its effect in the blood vessels of the lungs. The best known endogenous cannabinoid is anandamide. “Since our results show that anandamide dilates the bronchial tubes, we wanted to understand the exact mechanism behind it,” explains Daniela Wenzel.

    Enzyme degrades cannabinoid

    It quickly emerged that the two best-known receptors for anandamide (CB1 and CB2) are irrelevant for this regulation. Therefore, there must be an alternative signalling pathway through which the messenger substance anandamide acts on the bronchial tubes.

    Daniela Wenzel and her team showed that this alternative pathway uses an enzyme called fatty acid amide hydrolase (FAAH). FAAH degrades anandamide, producing e.g. arachidonic acid, which in turn is converted to prostaglandin E2. “We know that prostaglandin E2 can dilate the bronchial tubes,” points out Annika Simon. Prostaglandin E2 acts via certain receptors and leads to an increase in the messenger substance cAMP (cyclic adenosine monophosphate). “It is precisely this, the increase in cAMP, that is targeted by well-established inhalation medications against asthma,” says Daniela Wenzel. So, the goal is the same, but the path is different.

    Anandamide deficiency in asthma

    Wenzel and her team gradually deciphered the signalling pathway. They revealed that the enzyme FAAH is located both in the smooth muscle of the bronchial tubes and in the ciliated epithelium. The increase in cAMP after anandamide administration could be detected both in the mouse model and in human bronchial cells. In order to find out whether anandamide could also works in asthma patients, the team used a disease model in mice where certain substances can be used to create artificial asthma. In these animals, too, the administration of anandamide led to a widening of the bronchial tubes. “This means that asthma doesn’t result in resistance to anandamide,” explains Daniela Wenzel. Moreover, the researchers found that asthmatic animals have less anandamide and other endocannabinoids in their bronchial system than healthy animals. “Therefore, it’s possible that this anandamide deficiency is one of the causes of bronchial asthma,” concludes Daniela Wenzel.

    The discovery of the new signalling pathway could also open up new possibilities for intervening in the disease process. “But there’s still a long way to go, and it will certainly take several years,” stresses Daniela Wenzel. She expressly warns patients not to undertake experiments with cannabis plants. “We can’t draw any direct conclusions regarding plant cannabinoids from the findings on endogenous cannabinoids. Exactly which other ingredients are found in cannabis plants besides the known cannabinoids is entirely unclear. Plus, the plants sometimes contain harmful substances.” Nevertheless, the findings of this study are already pointing towards a better understanding of the body’s own cannabinoid system, which could lead to new treatment options for lung diseases in a few years’ time.

    Funding

    The study was funded by the German Research Foundation (funding code: WE4461/1-1).

    https://news.rub.de/english/press-releases/2022-11-17-medicine-bodys-own-cannabinoids-widen-bronchial-tubes

    Ruhr-Universitat Bochum

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  • Pulmonary Fibrosis Claims Life of R&B Singer B. Smyth

    Pulmonary Fibrosis Claims Life of R&B Singer B. Smyth

    Newswise — (November 18, 2022) — B. Smyth, 28, died on Nov. 17, 2022, after a long battle with pulmonary fibrosis, according to an Instagram post featuring his brother Denzil. The R&B singer, whose real name was Brandon Smith, recently released a single from his ICU bed.

    Pulmonary fibrosis (PF) is a progressive, debilitating disease that causes scarring in the lungs and does not presently have a cure. Though largely unknown, more than 250,000 Americans are currently living with the disease. The most common symptoms of PF include a chronic, dry cough, fatigue, and shortness of breath. Other symptoms include weakness, discomfort in the chest, loss of appetite and unexplained weight loss.

    “Our hearts go out to the loved ones of B. Smyth,” said William T. Schmidt, President and CEO of the Pulmonary Fibrosis Foundation (PFF). “Pulmonary fibrosis is a very serious disease, yet many patients have never heard of it prior to their diagnosis. The PFF is mobilizing people and resources to drive awareness and earlier diagnoses, and leading research so that we may ultimately have a cure for PF.”

    There are more than 50,000 new cases of pulmonary fibrosis diagnosed every year. While anyone can develop pulmonary fibrosis, it is more likely to occur in those 60 years and older with a history of smoking, putting hundreds of thousands of Americans at risk for the disease. Other risk factors include: a family history of pulmonary fibrosis; prior or current use of certain medications such as chemotherapy and amiodarone; a history of radiation treatment to the chest; environmental and occupational exposures including indoor mold, birds or asbestos; and a previous diagnosis of rheumatoid arthritis or another autoimmune disease.

    Those with symptoms or risk factors should speak with their healthcare provider. Early diagnosis is key to maximizing treatment options. To help start that conversation with a doctor, a downloadable Pulmonary Fibrosis Risk List is available at AboutPF.org.

    For more information or to find a pulmonologist near you, visit pulmonaryfibrosis.org.

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    About the Pulmonary Fibrosis Foundation

    The mission of the Pulmonary Fibrosis Foundation is to accelerate the development of new treatments and ultimately a cure for pulmonary fibrosis. Until this goal is achieved, the PFF is committed to advancing improved care of patients with PF and providing unequaled support and education resources for patients, caregivers, family members, and health care providers. The PFF has a three-star rating from Charity Navigator and is an accredited charity by the Better Business Bureau (BBB) Wise Giving Alliance. The Foundation has met all of the requirements of the National Health Council Standards of Excellence Certification Program® and has earned the Guidestar Platinum Seal of Transparency. For more information, visit pulmonaryfibrosis.org or call 844.TalkPFF (844.825.5733).

    Pulmonary Fibrosis Foundation

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  • Got the sniffles? Here’s how to make the right decision around family gatherings

    Got the sniffles? Here’s how to make the right decision around family gatherings

    Newswise — With what some are calling a “tripledemic” of COVID-19, the influenza virus and respiratory syncytial virus, or RSV, soaring in many parts of the country, the holiday season will come with some tough decisions again this year:

    Should you go to that Thanksgiving gathering even though you woke up with the sniffles? Send your child to that school performance even though she was coughing last night? Wear a mask to the grocery store after you learned your friend has COVID-19?

    New University of Colorado Boulder research, published in the journal PNAS Nexus, shows that when people simply take a moment to reflect on the consequences of their behavior they tend to choose options that impose fewer risks on other people.

    The international study of 13,000 people also found that, almost universally, people value others’ health and wellbeing.

    “Most people aspire to behave in a way that considers others’ wellbeing but often, in the moment, they behave more selfishly than they aspire to,” said senior author Leaf Van Boven, a professor of psychology and neuroscience at CU Boulder. “Our lab is trying to devise ways to help people better align their in-the-moment behavior with their values.”

    For the study, conducted at the height of the pandemic, Van Boven and collaborators in London, Austria, Singapore, Israel, Italy and Sweden presented participants in those countries and the United States with three hypothetical scenarios:

    In one, they owned a small restaurant and were considering reducing capacity as the virus surged.

    In another, they were supposed to meet with 50 friends for a birthday party after months of isolation but their government cautioned that, due to a COVID-19 surge, gatherings of 10 or more were unwise.

    In a third, they considered whether to cancel a planned Thanksgiving celebration with 30 family members, including older adults and young children.

    Before making a decision, half of study subjects were instructed to pause and practice a technique called “structured reflection,” developed in Van Boven’s lab, aimed at helping people be more mindful of their own values.

    They asked themselves two questions contrasting how their decision would impact them personally vs. how it would impact public health. For instance, in the Thanksgiving scenario, they asked,

    “How much (on a scale of 1 to 7) should your decision be influenced by the likelihood that COVID-19 may spread among family members?” And “How much should your decision be influenced by your satisfaction of spending time with family members?”

    Across all countries, cultures, ages and political parties, almost everyone gave at least equal weight to others’ wellbeing.

    “That’s encouraging,” said Van Boven. “Our study and others suggest it is a universal human tendency that people believe they should care about how their behavior affects other people.”

    Those in the structured reflection group were significantly more likely to say they would cancel Thanksgiving, and in the other scenarios they were more likely to err on the side of minimizing public health risks.

    Van Boven said that such techniques could be applied to achieve a host of public health goals in which in-the-moment personal benefit tends to overshadow broader public health considerations.

    “People know that they should not text while driving, that it’s better for the planet if they take the bus instead of drive, that they should eat more vegetables and exercise, but knowing is only the first step,” Van Boven said.

    While public health campaigns often focus on changing people’s minds, Van Boven’s team takes a different approach: to help people be their best selves and do what they already know they should do.

    As COVID-19 restrictions lift, such personal responsibility will grow increasingly important, he said.

    “I would encourage everyone to develop a habit of asking themselves when they are considering any sort of large social gathering: What is the risk you might impose on other people and is the benefit of the gathering worth the risk?”

    University of Colorado Boulder

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  • In lung cancer, proteins may predict prognosis, improve treatment, diagnostics

    In lung cancer, proteins may predict prognosis, improve treatment, diagnostics

    Newswise — Bethesda, Md. – Lung cancer is the leading cause of cancer deaths globally and a top cause of cancer deaths in the Military Health System. However, the ability to determine which of these patients have aggressive tumors and which will respond better to certain treatments – could soon be available through the collective analysis of proteins and genomes, according to a new study published Nov. 15 in Cell Reports Medicine, led by researchers at the Uniformed Services University (USU).

    The researchers sought to make advancements in this highly lethal cancer by looking specifically at the process through which genes (DNA) are converted to the messenger transcript (RNA), in cells, thus making proteins – a process known as the Central Dogma of Molecular Biology. When things go wrong during this process, the signal can change, thus turning healthy cells into cancer. In this study, the researchers analyzed all aspects of this process by applying several large scale technologies – whole genome sequencing, RNA sequencing, and proteomic profiling – to the most common type of lung cancer, lung adenocarcinoma. Ultimately, by bioinformatics data analysis of the DNA, RNA, protein, and phosphoprotein in cells – or what they refer to as proteogenomic characterization – they were able to connect certain molecular features of tumors with patient survivability, which could help better predict a patient’s outcome and inform clinical management.

    As a result of this analysis, the researchers also suggest their findings could lead to improved diagnostics, explained Dr. Matthew Wilkerson, one of the study’s co-authors and an associate professor in USU’s Department of Anatomy, Physiology, and Genetics, and Director of the Data Science Division in USU’s Center for Military Precision Health.

    “Our results show that patient survival can be well-predicted by protein levels in tumors, which may enable molecular diagnostics in smaller biopsies and tissue available in the clinic, which are otherwise challenging,” Wilkerson said. 

    The researchers also identified new tumor characteristics related to immune cells and regulatory networks through this proteogenomic characterization analysis. Therefore, this analysis could be used to help pinpoint which tumors may respond best to certain immunotherapies, thus improving patient treatment outcomes, Wilkerson said. 

    Furthermore, the analysis uncovered an entirely new molecular subtype of lung cancer. While previous studies have characterized lung cancer in those who are current smokers and those who have never smoked, this study found a third group, which turned out to be dominated by structural alterations – the disorganized genome – and former smokers. Ultimately, this suggests that not only if you smoked, but when you smoked affects the type of tumor you develop.

    The study, “Proteogenomic analysis of lung adenocarcinoma reveals tumor heterogeneity, survival determinants and therapeutically-relevant pathways,” was part of the Applied Proteogenomics Organizational Learning and Outcomes (APOLLO) network, a collaboration that launched in 2016 in response to the White House’s Cancer Moonshot initiative. APOLLO is led by USU’s Murtha Cancer Center (MCC)/Research Program (MCCRP), and is a collaboration between the National Cancer Institute, the Department of Defense, and the Department of Veterans Affairs, and is aimed at incorporating proteogenomics into patient care.

    Through APOLLO, additional studies are underway, using proteogenomics to analyze all aspects of the Central Dogma of Molecular Biology in hopes of improving care for many other forms of cancer. 

    “This work is significant because these are novel findings that have been identified through using multiple molecular platforms looking at DNA, RNA, and protein expression on a highly characterized lung adenocarcinoma sample collection that have led to a new understanding of both the biology of lung adenocarcinoma as well as potential therapeutic targets for the disease,” said Dr. Craig Shriver, co-author on the study and director of USU’s MCCRP.

    “A unique strength of this study is the comprehensive clinical data and follow-up from a U.S. cohort,” added Dr. Robert Browning, co-author on the study and a professor of Medicine at USU. “By avoiding potentially wide variations in medical practice with predominantly international cohorts we greatly increased confidence in the survival and outcome results for the study,” Browning said.

    “It was the combination of this exceptional clinical data to the unparalleled array of multi-omic analysis that led to one of the major findings of the study,” Browning said. “This discovery of a new subtype of lung adenocarcinoma, associated with former smokers that are often excluded from current lung cancer screening criteria, yet with some of the least treatable lung adenocarcinoma mutations and very poor survival, may provide broad translational applications in potential prevention pathway targets, screening markers and precision treatment in the very near future.”

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    About the Uniformed Services University of the Health Sciences: The Uniformed Services University of the Health Sciences, founded by an act of Congress in 1972, is the nation’s federal health sciences university and the academic heart of the Military Health System. USU students are primarily active-duty uniformed officers in the Army, Navy, Air Force and Public Health Service who receive specialized education in tropical and infectious diseases, TBI and PTSD, disaster response and humanitarian assistance, global health, and acute trauma care. USU also has graduate programs in oral biology, biomedical sciences and public health committed to excellence in research. The University’s research program covers a wide range of areas important to both the military and public health. For more information about USU and its programs, visit www.usuhs.edu.

    Uniformed Services University of the Health Sciences (USU)

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  • Incluso en los estados con leyes estrictas sobre el albuterol de reserva, los administradores escolares temen la responsabilidad

    Incluso en los estados con leyes estrictas sobre el albuterol de reserva, los administradores escolares temen la responsabilidad

    Newswise — LOUISVILLE, Kentucky (10 de noviembre de 2022) – Aunque el asma es una de las afecciones respiratorias más comunes en los niños, estos no siempre llevan consigo sus inhaladores o ni siquiera saben que tienen asma. Las legislaturas estatales han implementado programas de inhaladores de reserva para garantizar que las escuelas dispongan de un alivio del asma, como el albuterol, que pueda ser utilizado por cualquier niño que experimente dificultades respiratorias en el entorno escolar. Un nuevo estudio que se presenta en la Reunión Científica Anual del Colegio Estadounidense de Alergia, Asma e Inmunología (ACAAI, por sus siglas en inglés) de este año en Louisville, Kentucky, muestra que incluso en los estados con fuertes leyes de inhaladores/albuterol de reserva, los administradores escolares y los médicos prescriptores temen la responsabilidad al prescribir y administrar los inhaladores de reserva.

    “Tener un inhalador de alivio del asma, como el albuterol, a disposición de cualquier niño que pueda estar experimentando dificultades respiratorias es vital para hacerles frente a los síntomas del asma o a las emergencias que puedan presentarse durante la jornada escolar”, dice la alergista Andrea A. Pappalardo, MD, miembro del ACAAI y autora principal del estudio. “Queríamos examinar las barreras y los facilitadores de los programas de inhaladores de reserva en las escuelas de Illinois y en todos los estados con una legislación similar para entender mejor cómo podemos mejorar el acceso a los medicamentos en todo nuestro estado, y en todo el país”.

    Los investigadores llevaron a cabo 20 entrevistas a partes interesadas clave con enfermeras, médicos y administradores de escuelas en Illinois y descubrieron que el 35 % de los entrevistados citaron la dificultad para obtener prescripciones para inhaladores de reserva como una barrera para la implementación. La preocupación por la responsabilidad es uno de los motivos que explican la imposibilidad de conseguir prescripciones.

    “A pesar de que Illinois tiene una redacción sólida para proteger a los prescriptores de inhaladores de reserva y a los que administran inhaladores de reserva, los prescriptores siguen siendo cautelosos a la hora de proporcionar una prescripción para inhaladores de reserva y suministros relacionados a los distritos escolares. Sin prescripción, los inhaladores de reserva no pueden implementarse en las escuelas. La mejora de la educación y la palabrería relacionada con la responsabilidad aliviarán estas preocupaciones y mejorarán la aceptación de los inhaladores de reserva en Illinois, y en otros estados”, dice la Dra. Pappalardo. “Los programas de inhaladores de reserva proporcionan un acceso crítico a los inhaladores de alivio en las escuelas, donde los niños pasan la mayor parte del día. Los niños y el personal pueden beneficiarse de tener un inhalador de reserva disponible cuando no hay uno en la escuela para esa persona debido a la falta de diagnóstico, al olvido en casa o a la imposibilidad de obtener un inhalador por una multitud de asuntos relacionados con el acceso. Disponer de medicamentos que pueden salvar la vida, tanto para las emergencias asmáticas como para los síntomas cotidianos, es fundamental para mantener a nuestros niños en clase, donde deben estar”.

    Título del resumen: Responsabilidad: una barrera incomprendida para la implementación del albuterol de reserva en las escuelas de Illinois

    Presentadora: Andrea A. Pappalardo, MD

    Para obtener más información sobre el tratamiento del asma y el control de los síntomas del asma, o para encontrar un alergista en su zona, visite AllergyandAsthmaRelief.org. Reunión Científica Anual del ACAAI, del 10 al 14 de noviembre. Para conocer más noticias e investigaciones de la Reunión Científica del ACAAI, visite nuestra sala de prensa y siga la conversación en Twitter #ACAAI22.

    Acerca del ACAAI

    El ACAAI es una organización médica profesional de más de 6,000 alergistas inmunólogos y profesionales paramédicos, con sede en Arlington Heights, Illinois. El Colegio fomenta una cultura de colaboración y simpatía en la que sus miembros trabajan juntos y con otros para alcanzar los objetivos comunes de atención al paciente, educación, divulgación e investigación. Los alergistas del ACAAI son médicos certificados por la junta, capacitados para diagnosticar alergias y asma, administrar inmunoterapia y brindarles a los pacientes los mejores resultados de tratamiento. Para obtener más información y encontrar alivio, visite AllergyandAsthmaRelief.org. Síganos en Facebook, Pinterest y Twitter.

    American College of Allergy, Asthma and Immunology (ACAAI)

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  • Solutions to Tackling Smoking Rates

    Solutions to Tackling Smoking Rates

    Newswise — Every year, the Great American Smokeout draws attention to preventing deaths and chronic illness caused by smoking. Almost 38 million Americans, including nearly one million in New Jersey, still smoke tobacco and about half of all smokers die from smoking-related illnesses.

    Here, Michael Steinberg, professor and chief in the Division of General Internal Medicine at Robert Wood Johnson Medical School and Medical Director of the Rutgers Center for Tobacco Studies, which operates the Tobacco Dependence Program to help people quit tobacco, and Andrea Villanti, associate professor in the Department of Health Behavior, Society and Policy at the Rutgers School of Public Health and Deputy Director of the Rutgers Center for Tobacco Studies, discuss challenges to change smoking rates.

     

    Smoking rates have significantly dropped over time. Why should we still be concerned about trends in tobacco use?

    Villanti: While the rates of cigarette smoking have declined over the past several decades, we know those gains have been inconsistent. In a study published in JAMA Network Open, we found high smoking prevalence and lower quit ratios in rural versus urban areas. In addition to where people live, other research shows there are disparities in tobacco use based on social and demographic factors such as race and ethnicity, age, sexual orientation, disability status, socioeconomic status and/or behavioral health status.

    Steinberg: Related to this, we know there still a lot of work to be done to decrease tobacco use in patients with substance use disorder, depression and other psychiatric conditions, who continue to use tobacco at much higher rates than the general public. In our own research, we found that while most psychiatrists ask patients if they smoke, advise quitting and assess willingness to quit, a much smaller percent of psychiatrists assist patients with establishing quit plans or arranging for follow up. There are many competing priorities for health professionals; we want them to know they can refer patients to quitting resources like the Rutgers’ Tobacco Dependence Program or any of New Jersey’s 11 Quit Centers.

     

    Why is now a good time to quit?

    Steinberg: In addition to providing a time for people to quit during the Great American Smokeout on November 17, fall and winter can bring a surge of flu and COVID-19 cases, which are contagious respiratory illnesses. Smoking reduces lung capacity and increases the risk for respiratory infections. Quitting smoking can result in immediate benefits to health.

     

    How has the COVID-19 pandemic impacted tobacco treatment delivery?

    Steinberg: The COVID-19 pandemic posed challenges to all types of health care delivery but it also resulted in new opportunities. In a study conducted across 34 National Cancer Institute–designated cancer centers, including Rutgers Cancer Institute of New Jersey, we found that centers that adopted telehealth practices were able to maintain tobacco treatment for patients who smoke. Here at Rutgers, we continue to offer one-on-one and group counseling in both virtually and in-person.

    Villanti: Text messaging interventions can also be another way to help people quit smoking, particularly people not currently accessing tobacco treatment. In a randomized controlled trial, we found that low-income young adults engaging in a 12-week tailored text message smoking cessation intervention produced greater smoking abstinence than referral to online quit resources. Smokefree.gov offers a variety of free and tailored text messaging programs that provide help on-demand and around the clock. Some states also provide text messaging assistance through their tobacco quitlines.

     

    What advice do you have for people who want to quit using tobacco?

    Steinberg: We encourage people with an interest in quitting to reach out. Whether it is for your health, your wallet, your family or just not wanting to be addicted any longer, this is a great time to make the effort to stop – and we can help!

    Villanti: Use every tool in the toolbox! Counseling, medication, support from friends and family, quitlines and above all, the willingness to keep trying even if you slip. It’s hard to quit using tobacco, but every try counts.

    Rutgers University-New Brunswick

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  • Protein insights may boost lung cancer detection and treatment

    Protein insights may boost lung cancer detection and treatment

    Newswise — Scientists investigating the mechanics of the early stages of lung cancer have identified a new potential treatment, which could also aid early detection of the disease.

    Levels of a key protein – called TLR2 – in tumours was found to predict a patient’s survival after being diagnosed with lung cancer, a study shows.

    A drug compound that activates TLR2 was tested in mice and was found to reduce tumour growth in the early stages of the disease.

    With the five-year survival rate from late stage lung cancer only six per cent – compared with 50 per cent when diagnosed earlier – experts say the breakthrough could help spot the disease sooner and improve patient outcomes.

    A group, led by researchers from the University of Edinburgh, discovered that TLR2 helps control some of the body’s defense mechanisms when cancerous mutations occur in cells.

    The protein is linked with senescence, a process whereby cells stop growing and secrete a variety of chemicals and other proteins which collectively act as warning signals and defences against cancer.

    Senescent cells are present in early lung cancers, but are no longer present in late-stage cancers, suggesting that senescence can prevent cancer progression.

    Having identified TLR2’s importance, the team used data from human tumour samples to confirm that patients with high levels of the protein in the early stages of lung cancer had increased survival compared to those who had lower levels.

    The team then used a drug known to activate TLR2 in a mouse model of lung cancer. Researchers found that the drug reduced lung tumour growth.

    Experts hope these findings could lead to research into using senescence and the associated secreted chemicals as part of a screening programme to provide earlier lung cancer diagnosis.

    Further research is needed, the team adds, such as clinical trials to confirm whether the drug is effective in humans.

    The research is a collaboration between researchers from University of Edinburgh, University College London, University of Cantabria in Spain, the Spanish National Research Council and the Mayo Clinic in the USA.

    The study is published in Cell Reports. It was funded by Cancer Research UK, Wellcome, the Ministry of Science and Innovation of the Government of Spain and the US National Institute of Aging.

    Dr Fraser Millar, Clinical Lecturer in Respiratory Medicine at the University of Edinburgh, said: “I think these results are really exciting. Very little is known about the biology of early lung cancer and by understanding this process more we have identified a possible new treatment for this devastating disease. This project highlights the value of basic science research and how this can be translated into new treatments for patients.”

    University of Edinburgh

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  • New treatment can significantly increase the efficacy of chemotherapy and prevent metastasis

    New treatment can significantly increase the efficacy of chemotherapy and prevent metastasis

    • The researchers identified a mechanism that generated a cancer-promoting inflammatory environment in response to chemotherapy. Based on this discovery, they developed a treatment combination that reduced the incidence of lung metastasis following chemotherapy from 52% to only 6%.

    Newswise — A new treatment developed at Tel Aviv University may significantly enhance the efficacy of chemotherapy in breast cancer patients, reducing the risk for lung metastasis following chemo from 52% to only 6%. Conducted in an animal model, the study identified the mechanism that generates a cancer-promoting inflammatory environment in response to chemotherapy. Moreover, the researchers found that by adding an anti-inflammatory agent to the chemotherapy, metastasis can be prevented.

    The study was led by Prof. Neta Erez of the Department of Pathology at TAU’s Sackler Faculty of Medicine, and researchers from her group: Lea Monteran, Dr. Nour Ershaid, Yael Zait, and Ye’ela Scharff, in collaboration with Prof. Iris Barshack of the Sheba Medical Center and Dr. Amir Sonnenblick of the Tel Aviv Sourasky (Ichilov) Medical Center. The paper was published in Nature Communications. The study was funded by ERC, the Israel Cancer Association, and the Emerson Cancer Research Fund.

    Prof. Erez: “In many cases of breast cancer, surgical removal of the primary tumor is followed by a chemotherapy regimen intended to kill any remaining malignant cells – either left behind by the surgeon or already colonizing in other organs. However, while effectively killing cancer cells, chemotherapy also has some undesirable and even harmful side effects, including damage to healthy tissues. The most dangerous of these is probably internal inflammations that might paradoxically help remaining cancer cells to form metastases in distant organs. The goal of our study was to discover how this happens and try to find an effective solution.”

    To this end, the researchers created an animal model for breast cancer metastasis. The animals received the same treatment as human patients: surgical removal of the primary tumor, then chemotherapy, followed by monitoring to detect metastatic relapse as early as possible. The disturbing results: metastatic tumors were detected in the lungs of a large percentage of the treated animals – similar to the percentage found in the control group.

    To decipher these adverse effects, the researchers examined the animals’ lungs at an intermediate stage – when tiny micro-metastases may have already developed, but even advanced imaging technologies like CT cannot detect them. Prof. Erez: “In humans this interval between chemotherapy and detection of metastatic tumors is an inaccessible ‘black box’. Working with an animal model we could check what actually happens inside this ‘box’. We discovered a previously unknown mechanism: the chemotherapy generates an inflammatory response in connective tissue cells called fibroblasts, causing them to summon immune cells from the bone marrow. This in turn creates an inflammatory environment that supports the micro-metastases, helping them grow into full-fledged metastatic tumors. In this way, the chemotherapy, administered as a means for combating cancer, achieves the opposite result.”

    The researchers also identified the mechanism through which fibroblasts recruit immune cells, and ‘train’ them to support the cancer. Prof. Erez: “We found that in response to chemotherapy, the fibroblasts secrete ‘complement proteins’ – proteins that mediate cell recruitment and intensify inflammation, often by summoning white blood cells to damaged or infected areas, a process called chemotaxis. When the immune cells reach the lungs, they create an inflammatory environment that supports cancer cells and helps them grow.”

    To combat this newly discovered process, the researchers combined the chemotherapy administered to the animals with a drug that blocks the activity of complement proteins. The results were very encouraging: following the combined treatment the percentage of animals developing no metastases rose from 32% to 67%; and the percentage of those with extensive cancer colonization in their lungs decreased from 52% with regular chemotherapy to 6% when the inflammation inhibitor was added.

    Prof. Erez concludes: “We discovered the mechanism behind a severe problem in the treatment of breast cancer: many patients develop metastatic tumors following removal of the primary tumor plus chemotherapy. We identified an inflammatory mechanism through which chemotherapy inadvertently supports the growth of metastatic tumors, and also discovered an effective solution: combining chemotherapy with an inflammation inhibitor. We hope that our findings will enable more effective treatment for breast cancer, and perhaps other types of cancer as well – to prevent metastatic relapse and save numerous lives worldwide.” 

     

    Link to the article:

    https://www.nature.com/articles/s41467-022-33598-x

    Tel Aviv University

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  • Cellular Cilium an Early Sign of Mesothelioma Differentiation

    Cellular Cilium an Early Sign of Mesothelioma Differentiation

    Newswise — A new study investigated the expression of the primary cilium in mesothelioma, finding that primary cilia is preferentially lost in the more aggressive subtype of mesothelioma and further research may confirm its potential prognostic and diagnostic value.

    This is the first evidence that different mesothelioma, characterized by different levels of aggressiveness, show a different pattern of primary cilium expression.  

    Primary cilium is an organelle protruding from the cell membrane that, like an antenna, collects signals from the extracellular space and transduces information into cells. Many tumors do not express the primary cilium thereby overriding its tumor suppressor function.

    Despite the importance of the primary cilium, there is still a lot to understand about its functions.

    The study, published in the journal Cancers, was directed by Antonio Giordano, M.D., Ph.D., Professor at the Department of Medical Biotechnology of the University of Siena and President of the Sbarro Health Research Organization (SHRO). 

    “With this study we have identified a possible marker of the heterogeneity of this orphan disease, mesothelioma, a tumor with still poor prognosis,” said prof. Giordano. “The improvement of existing treatments for mesothelioma is mainly hampered by the heterogeneity that characterizes it.”

    “This study underlines the importance of tailored therapies for mesothelioma patients,” said Cristiana Bellan, Professor at the Department of Medical Biotechnology of the University of Sien, “and in this context our analysis can help identify which patients could benefit from specific treatment.”

    Journal Reference:  Barbarino, M. et al. Analysis of Primary Cilium Expression and Hedgehog Pathway Activation in Mesothelioma Throws Back Its Complex Biology. Cancers 2022, 14, 5216. https://doi.org/10.3390/cancers14215216

     

    About the Sbarro Health Research Organization

    The Sbarro Health Research Organization (SHRO) is non-profit charity committed to funding excellence in basic genetic research to cure and diagnose cancer, cardiovascular diseases, diabetes and other chronic illnesses and to foster the training of young doctors in a spirit of professionalism and humanism. To learn more about the SHRO please visit www.shro.org

    Sbarro Health Research Organization (SHRO)

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  • Study Identifies Key T Cells for Immunity Against Fungal Pneumonia

    Study Identifies Key T Cells for Immunity Against Fungal Pneumonia

    Newswise — Researchers at the University of Illinois College of Veterinary Medicine have demonstrated in a mouse model that a specific type of T cell, one of the body’s potent immune defenses, produces cytokines that are necessary for the body to acquire immunity against fungal pathogens. This finding could be instrumental in developing novel, effective fungal vaccines.

    Despite vaccines being hailed as one of the greatest achievements of medicine, responsible for controlling or eradicating numerous life-threatening infectious diseases, no vaccines have been licensed to prevent or control human fungal infections.

    This lack proved especially deadly during the COVID-19 pandemic. In countries where steroids were widely used to suppress inflammation of the lungs, COVID-19 patients with preexisting conditions such as uncontrolled diabetes showed a greater likelihood of developing lethal fungal infections. 

    T Cells Could Produce Protective or Pathological Response

    “A particular type of T cell [TH17 cells] that expresses GM-CSF [granulocyte-macrophage colony-stimulating factor] was linked to greater severity of illness in people infected with the virus that causes COVID-19,” said Dr. Som Nanjappa, an assistant professor of immunology at the University of Illinois.

    “Our study shows that IL-17A+ CD8+ T cell (Tc17), which also expresses GM-CSF, is necessary for mediating fungal vaccine immunity without instigating hyperinflammation. So clearly, the antigen specificity of T cells—whether they target viral vs. fungal or bacterial pathogens—has a huge impact on whether they play a protective or detrimental role.”

    The article, “GM-CSF+ Tc17 cells are required to bolster vaccine immunity against lethal fungal pneumonia without causing overt pathology,” appeared in Cell Reports on October 25. Dr. Nanjappa’s coauthors on the study are Srinivasu Mudalagiriyappa, a former graduate student now a scientist with Insmed Incorporated, a global biopharmaceutical company focused on serious and rare diseases; Jaishree Sharma, a graduate student in the Department of Pathobiology; and Miranda D. Vieson, a Clinical Associate Professor in the Department of Pathobiology as well as a boarded veterinary pathologist in the college’s Veterinary Diagnostic Laboratory.

    T Cells for Fungal Vaccine Immunity

    In the study, colonies of mice were given an experimental fungal vaccine. The mice were then exposed to virulent fungal pathogen to cause lethal pulmonary infection. Researchers could determine the necessity of GM-CSF+ Tc17 cells to mediate vaccine immunity. Further, they found that IL-1 and IL-23 cytokines are necessary for eliciting GM-CSF+ Tc17 cells to vaccine. While IL-23 is dispensable for the long-term memory homeostasis of these cells, it is essential for vaccine immunity against pulmonary fungal infection.

    This study identifies a beneficial subset of T cells for fungal vaccine immunity that bolsters efforts to develop a vaccine platform containing suitable adjuvants to potentiate such a T cell subset.

    “In line with this, we have identified a functional phenotypic marker that could be targeted to enhance this subset to augment vaccine efficacy,” said Dr. Nanjappa. He recently received NIH-R01 funding to pursue this strategy for a fungal vaccine.   

    Read the study online: https://doi.org/10.1016/j.celrep.2022.111543

    University of Illinois at Urbana-Champaign

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  • Phage Trial to Treat CF Patients With Multi-Drug Resistant Bacterial Infections

    Phage Trial to Treat CF Patients With Multi-Drug Resistant Bacterial Infections

    Newswise — Cystic fibrosis (CF) is an inherited disorder that causes severe damage to the lungs and other organs in the body. Nearly 40,000 children and adults in the United States live with CF, an often difficult existence exacerbated by an opportunistic bacterium called Pseudomonas aeruginosa, which is a major cause of chronic, life-threatening lung infections.

    P. aeruginosa infections are not easily treated. The pathogen can be resistant to most current antibiotics. However, an early-stage clinical trial led by scientists at University of California San Diego School of Medicine, with collaborators across the country, has launched to assess the safety and efficacy of treating P. aeruginosa lung infections in CF patients with a different biological weapon: bacteriophages.

    Bacteriophages are viruses that have evolved to target and destroy specific bacterial species or strains. Phages are more abundant than all other life forms on Earth combined and are found wherever bacteria exist. Discovered in the early 20th century, they have long been investigated for their therapeutic potential, but increasingly so with the rise and spread of antibiotic-resistant bacteria.

    In 2016, scientists and physicians at UC San Diego School of Medicine and UC San Diego Health used an experimental intravenous phage therapy to successfully treat and cure colleague Tom Patterson, PhD, who was near death from a multidrug-resistant bacterial infection. Patterson’s was the first documented case in the U.S. to employ intravenous phages to eradicate a systemic bacterial infection. Subsequent successful cases helped lead to creation of the Center for Innovative Phage Applications and Therapeutics (IPATH) at UC San Diego, the first such center in North America.

    In 2020, IPATH researchers published data from 10 cases of intravenous bacteriophage therapy to treat multidrug-resistant bacterial infections, all at UC San Diego. In 7 of 10 cases, there was a successful outcome.

    The new phase 1b/2 clinical trial advances this work. The trial is co-led by Robert Schooley, MD, professor of medicine and an infectious disease expert at UC San Diego School of Medicine who is co-director of IPATH and helped lead the clinical team that treated and cured Patterson in 2016.

    It will consist of three elements, all intended to assess the safety and microbiological activity of a single dose of intravenous phage therapy in males and non-pregnant females 18 years and older, all residing in the United States.

    The dose is a cocktail of four phages that target P. aeruginosa, a bacterial species commonly found in the environment (soil and water) that can cause infections in the blood, lungs and other parts of the body after surgery.

    For persons with CF, P. aeruginosa is a familiar and sometimes fatal foe. The Cystic Fibrosis Foundation estimates that roughly half of all people with CF are infected by Pseudomonas. Previous studies have indicated that chronic P. aeruginosa lung infections negatively impact life expectancy of CF patients, who currently live, on average, to approximately 44 years.

    In the first stage of the trial, two “sentinel subjects” will receive one of three dosing strengths of the IV bacteriophage therapy. If, after 96 hours and no adverse effects, the second stage (2a) will enroll 32 participants into one of four arms: the three doses and a placebo.

    After multiple follow-up visits over 30 days and an analysis of which dosing strength exhibited the most favorable safety and microbiologic activity, i.e. most effective at reducing P. aeruginosa, stage 2b will recruit up to 72 participants to either receive that IV dose or a placebo.

    Enrollment will occur at 16 cystic fibrosis clinical research sites in the United States, including UC San Diego. It is randomized, double-blind and placebo-controlled. The trial is being conducted through the Antibacterial Resistance Leadership Group and funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, with additional support for the UC San Diego trial site from the Mallory Smith Legacy Fund.

    Mallory Smith was born with cystic fibrosis and died in 2017 at the age of 25 from a multidrug-resistant bacterial infection following a double lung transplant.

    “Mallory’s death was a preventable tragedy,” said her mother, Diane Shader Smith. “We are supporting the IPATH trial through Mallory’s Legacy Fund because Mark and I deeply believe in the promise of phage therapy to save lives by combatting multidrug-resistant bacteria.”

    In an article published in 2020 in Nature Microbiology, Schooley and Steffanie Strathdee, PhD, associate dean of global health sciences and Harold Simon Professor in the Department of Medicine and IPATH co-director, describe phages as “living antibiotics.”

    As such, said Schooley, researchers need to learn how to best use them to benefit patients through the same systematic clinical trials employed to evaluate traditional antibiotics.

    The primary objectives of the new trial are first to determine the safety of a single IV phage dose in clinically stable patients with CF who are also infected with P. aeruginosa, said Schooley.

    “Second, it’s to describe the microbiological activity of a single IV dose and third, to assess the benefit-to-risk profile for CF patients with P. aeruginosa infections. This is one study, with a distinct patient cohort and carefully prescribed goals. It’s a step, but an important one that can, if ultimately proven successful, help address the growing, global problem of antimicrobial resistance and measurably improve patients’ lives.”

    Estimated study completion date is early 2025.

    For more information on the clinical trial and participant eligibility criteria, visit clinicaltrials.gov or visit IPATH and click on the Contact Us button.

    # # #

    University of California San Diego

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  • Vaccination status, mortality among intubated patients with COVID-19–related acute respiratory distress syndrome

    Vaccination status, mortality among intubated patients with COVID-19–related acute respiratory distress syndrome

    About The Study: Full vaccination status compared with controls was associated with lower mortality among critically ill patients who required invasive mechanical ventilation owing to COVID-19–related acute respiratory distress syndrome in this study including 265 patients. These results may inform discussions with families about prognosis.

    Authors: Ilias I. Siempos, M.D., D.Sc., of the National and Kapodistrian University of Athens Medical School in Athens, Greece, is the corresponding author.

    To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/  

    (doi:10.1001/jamanetworkopen.2022.35219)

    Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

    #  #  #

    Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time http://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2022.35219?utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_term=100722

    About JAMA Network Open: JAMA Network Open is the new online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication.

    JAMA – Journal of the American Medical Association

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  • Better Asthma and COPD Drugs with Fewer Side Effects Are Within Reach

    Better Asthma and COPD Drugs with Fewer Side Effects Are Within Reach

    Rockville, Md. (September 29, 2022)—Bronchodilators, the most common type of asthma-fighting drug, inhibits contractions of airway smooth muscle that are induced by stimulating receptors on the muscle’s surface. New research highlights a novel mechanism for the drugs and will aid in the development of better medications for the treatment of asthma and chronic obstructive pulmonary disease (COPD). The findings are detailed in a new article by researchers from Dundalk Institute of Technology in Ireland and Queen’s University in Northern Ireland. 

    Asthma and COPD are common lung disorders—caused by excessive constriction of the airways—that make breathing difficult. Bronchodilators,  also known as beta-adrenoceptor agonists, relax airway smooth muscle and open the airways to make breathing easier. These drugs bind to beta-adrenoceptors located on airway muscle cells and cause them to relax.

    Constriction of the airways is regulated in the nerves, which release a chemical called acetylcholine. This chemical causes the airways to constrict and narrow. For patients with COPD, the constrictor effects of acetylcholine are enhanced. It has been long known that beta-adrenoceptor agonists could reverse the constricting effects of acetylcholine on airway smooth muscle, but it has not been fully clear how this occurs. It is important to understand how these medications work to assist with future development of more effective drugs with fewer side effects.

    Read the full article, “M2 muscarinic receptor-dependent contractions of airway smooth muscle are inhibited by activation of β-adrenoceptors,” published ahead of print in Function. Contact APS Media Relations or call 301.634.7314 to schedule an interview with a member of the research team.

     

     

    American Physiological Society (APS)

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