E-cigarette vapour disables lung's protective cells

Agencies
August 14, 2018

London, Aug 14: E-cigarette vapour disables key immune cells in the lung that keep the air spaces clear of potentially harmful particles, say scientists who warn that vaping may be more harmful than traditional smoking.

The vapour impairs the activity of alveolar macrophages, which engulf and remove dust particles, bacteria, and allergens that have evaded the other mechanical defences of the respiratory tract.

The findings, published online in the journal Thorax, suggest that while further research is needed to better understand the long term health impact of vaping, e-cigarettes may be more harmful than we think, as some of the effects were similar to those seen in regular smokers and people with chronic lung disease.

Vaping is increasing in popularity, but most of the current body of research has focused on the chemical composition of e-cigarette liquid before it is vaped.

Researchers from the University of Birmingham and Swansea University in the UK devised a mechanical procedure to mimic vaping and produce condensate from the vapour.

They extracted alveolar macrophages from lung tissue samples provided by eight non-smokers who had never had asthma or chronic obstructive pulmonary disease (COPD).

A third of the cells were exposed to plain e-cigarette fluid, a third to different strengths of the artificially vaped condensate with and without nicotine, and a third to nothing for 24 hours.

The results showed that the condensate was significantly more harmful to the cells than e-cigarette fluid and that these effects worsened as the 'dose' increased.

After 24 hours of exposure, the total number of viable cells exposed to the vaped condensate was significantly reduced compared to the untreated cells, and condensate containing nicotine exaggerated this effect.

Exposure to the condensate increased cell death and boosted production of oxygen free radicals by a factor of 50, and it significantly increased the production of inflammatory chemicals - more so when the condensate contained nicotine.

What is more, the ability of cells exposed to vaped condensate to engulf bacteria was significantly impaired, although treatment with an antioxidant restored this function and helped lessen some of the other harmful effects.

The researchers conclude that the vaping process itself can damage vital immune system cells, at least under laboratory conditions.

"Importantly, exposure of macrophages to [e-cigarette vapour condensate] induced many of the same cellular and functional changes in [alveolar macrophage] function seen in cigarette smokers and patients with COPD," they said. 

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Agencies
February 6,2020

Researchers have found the rates of lung cancer are higher in young women than men.

The study, published in the journal Pediatrics, examined lung cancer rates in young adults in 40 countries across five continents and uncovered a trend of higher lung cancer rates in women compared with men in recent years.

The emerging trend was widespread, affecting countries across varied geographic locations and income levels.

The changes appeared to be driven by a rising rate of adenocarcinoma lung cancer among women, said the study researchers from University of Calgary in Canada.

Lung cancer rates have been higher among men than women because men started smoking in large numbers earlier and smoked at higher rates; however, recent studies have reported converging lung cancer incidence rates between sexes.

Among men, age specific lung cancer incidence rates generally decreased in all countries, while in women the rates varied across countries with the trends in most countries stable or declining, albeit at a slower pace compared to those in men.

For the findings, lung and bronchial cancer cases between 30-64 age group from 1993-2012 were extracted from cancer incidence in five continents.

The study found the higher emerging rates of lung cancer in young women compared to young men.

According to the researchers, future studies are needed to identify reasons for the elevated incidence of lung cancer among young women.

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Agencies
July 3,2020

Apart from the many benefits of doing exercise, new research has now found that exercise can slow down or prevent the development of macular degeneration and may benefit other common causes of vision loss, such as glaucoma and diabetic retinopathy.

The new study from the University of Virginia School of Medicine found that exercise reduced the harmful overgrowth of blood vessels in the eyes of lab mice by up to 45 per cent. This tangle of blood vessels is a key contributor to macular degeneration and several other eye diseases.

The study represents the first experimental evidence showing that exercise can reduce the severity of macular degeneration, a leading cause of vision loss, the scientists report. Ten million Americans are estimated to have the condition.

"There has long been a question about whether maintaining a healthy lifestyle can delay or prevent the development of macular degeneration. The way that question has historically been answered has been by taking surveys of people, asking them what they are eating and how much exercise they are performing," said researcher Bradley Gelfand, PhD, of UVA's Center for Advanced Vision Science.

"That is basically the most sophisticated study that has been done. The problem with that is that people are notoriously bad self-reporters ... and that can lead to conclusions that may or not be true. This [study] offers hard evidence from the lab for the very first time," Gelfand added.

Enticingly, the research found that the bar for receiving the benefits from exercise was relatively low - more exercise didn't mean more benefit.

"Mice are kind of like people in that they will do a spectrum of exercise. As long as they had a wheel and ran on it, there was a benefit. The benefit that they obtained is saturated at low levels of exercise," Gelfand said.

An initial test comparing mice that voluntarily exercised versus those that did not found that exercise reduced the blood vessel overgrowth by 45%. A second test, to confirm the findings, found a reduction of 32 per cent.

The scientists aren't certain exactly how exercise is preventing the blood vessel overgrowth. There could be a variety of factors at play, they say, including increased blood flow to the eyes.

Gelfand, of UVA's Department of Ophthalmology and Department of Biomedical Engineering, noted that the onset of vision loss is often associated with a decrease in exercise.

"It is fairly well known that as people's eyes and vision deteriorate, their tendency to engage in physical activity also goes down. It can be a challenging thing to study with older people. ... How much of that is one causing the other?" he said.
The researchers already have submitted grant proposals in hopes of obtaining funding to pursue their findings further.

"The next step is to look at how and why this happens, and to see if we can develop a pill or method that will give you the benefits of exercise without having to exercise," Gelfand said.

He explained, "We're talking about a fairly elderly population [of people with macular degeneration], many of whom may not be capable of conducting the type of exercise regimen that may be required to see some kind of benefit." (He urged people to consult their doctors before beginning any aggressive exercise program.)
Gelfand, a self-described couch potato, disclosed a secret motivation for the research: "One reason I wanted to do this study was sort of selfish. I was hoping to find some reason not to exercise," he joked. "It turned out exercise really is good for you."

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Agencies
July 2,2020

The American pharmaceutical giant Pfizer Inc. and the European biotechnology company BioNTech SE have conducted an experimental trial of a COVID-19 vaccine candidate and found it to be safe, well-tolerated, and capable of generating antibodies in the patients.

The study, which is yet to be peer-reviewed, describes the preliminary clinical data for the candidate vaccine -- nucleoside-modified messenger RNA (modRNA), BNT162b1.

It said the amount of antibodies produced in participants after they received two shots of the vaccine candidate was greater than that reported in patients receiving convalescent plasma from recovered COVID-19 patients.

"I was glad to see Pfizer put up their phase 1 trial data today. Virus neutralizing antibody titers achieved after two doses are greater than convalescent antibody titers," tweeted Peter Hotez, a vaccine scientist from Baylor College of Medicine in the US, who was unrelated to the study.

Researchers, including those from New York University in the US, who were involved in the study, said the candidate vaccine enables human cells to produce an optimised version of the receptor binding domain (RBD) antigen -- a part of the spike (S) protein of SARS-CoV-2 which it uses to gain entry into human cells.

"Robust immunogenicity was observed after vaccination with BNT162b1," the scientists noted in the study.

They said the program is evaluating at least four experimental vaccines, each of which represents a unique combination of mRNA format and target component of the novel coronavirus, SARS-CoV-2.

Based on the study's findings, they said BNT162b1 could be administered in a quantity that was well tolerated, potentially generating a dose dependent production of immune system molecules in the patients.

The research noted that patients treated with the vaccine candidate produced nearly 1.8 to 2.8 fold greater levels of RBD-binding antibodies that could neutralise SARS-CoV-2.

"We are encouraged by the clinical data of BNT162b1, one of four mRNA constructs we are evaluating clinically, and for which we have positive, preliminary, topline findings," said Kathrin U. Jansen, study co-author and Senior Vice President and Head of Vaccine Research & Development, Pfizer.

"We look forward to publishing our clinical data in a peer-reviewed journal as quickly as possible," Jansen said.

According to Ugur Sahin, CEO and Co-founder of BioNTech, and another co-author of the study, the preliminary data are encouraging as they provide an initial signal that BNT162b1 is able to produce neutralising antibody responses in humans.

He said the immune response observed in the patients treated with the experimental vaccine are at, or above, the levels observed from convalescent sera, adding that it does so at "relatively low dose levels."

"We look forward to providing further data updates on BNT162b1," Sahin said.

According to a statement from Pfizer, the initial part of the study included 45 healthy adults 18 to 55 years of age.

It said the priliminary data for BNT162b1 was evaluated in 24 subjects who received two injections of 10 microgrammes ( g) and 30 g -- 12 subjects who received a single injection of 100 g, and 9 subjects who received two doses of a dummy vaccine.

The study noted that participants received two doses, 21 days apart, of placebo, 10 g or 30 g of BNT162b1, or received a single dose of 100 g of the vaccine candidate.

According to the scientists, the highest neutralising concentrations of antibodies were observed seven days after the second dose of 10 g, or 30 g on day 28 after vaccination.

They said the neutralising concentrations were 1.8- and 2.8-times that observed in a panel of 38 blood samples from people who had contracted the virus.

In all 24 subjects who received two vaccinations at 10 g and 30 g dose levels, elevation of RBD-binding antibody concentrations was observed after the second injection, the study noted.

It said these concentrations are 8- and 46.3-times the concentration seen in a panel of 38 blood samples from those infected with the novel coronavirus.

At the 10 g or 30 g dose levels, the scientists said adverse reactions, including low grade fever, were more common after the second dose than the first dose.

According to Pfizer, local reactions and systemic events after injection with 10 g and 30 g of BNT162b1 were "dose-dependent, generally mild to moderate, and transient."

It said the most commonly reported local reaction was injection site pain, which was mild to moderate, except in one of 12 subjects who received a 100 g dose, which was severe.

The study noted that there was no serious adverse events reported by the patients.

Citing the limitations of the research, the scientists said the immunity generated in the participants in the form of the T cells and B cells of their immune system, and the level of immunity needed to protect one from COVID-19 are unknown.

With these preliminary data, along with additional data being generated, Pfizer noted in the statement that the two companies will determine a dose level, and select among multiple vaccine candidates to seek to progress to a large, global safety and efficacy trial, which may involve up to 30,000 healthy participants if regulatory approval to proceed is received.

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