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diagram showing influences of genetic and environmental factors in asthma

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image showing association of polymorphism gene with clinical variability in cystic fibrosis patients

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link between genetic polymorphism on gene PTPN22 and cystic fibrosis

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An updated meta-analysis of transforming growth factor-β1 gene: Three well-characterized polymorphisms with asthma. - PubMed - NCBI

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link between specific genetic polymorphisms and asthma risk

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An updated meta-analysis of transforming growth factor-β1 gene: Three well-characterized polymorphisms with asthma. - PubMed - NCBI

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Genetic Polymorphisms

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Polymorphism: Polymorphism,, in biology, a discontinuous genetic variation resulting in the occurrence of several different forms or types of individuals among the members of a single species. A discontinuous genetic variation divides the individuals of a population into two or more sharply distinct forms. The

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studying the association between polymorphisms/phenotype for severity of lung impairment

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current cystic fibrosis treatments

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Read about the main treatments for cystic fibrosis, including medications, airway clearance techniques, nutritional advice and lung transplants.

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vitamin D supplements/injections of benralizumab

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Some of the 24 million people in the U.S. with asthma, or inflammation that narrows the airways, suffer severe symptoms: Like persistent shortness of breath. The inability to speak in full sentences. Or a chest that feels closed. Two new studies tout possible new treatments for severe asthma.
Highlights from the interview with Dr. Joseph Austin, a pulmonologist with Texas Health Arlington Memorial Hospital:
One study indicates oral supplements of vitamin D may help with severe asthma: "The claim is that it reduces inflammation As a result, patients with asthma or potential for other infectious diseases are reduced. The overall thinking is that the vitamin D is the "new drug" and it's being tested for various things and one of them is chronic inflammation. The overall consensus is that it probably doesn't have the effect that some people actually say it does."

You can get vitamin-d from food sources, the sun. Would more of either work or does it have to be an oral supplement? "Kind of interesting because it's a fat soluble vitamin that stores in the body in various concentrations. Most of the research on it centers around a disease known as rickets, which we don't see much of in our country. It is present in some of the Third World countries where they don't have milk products and other types of food that would be rich in vitamin-D. There is also the principle that sun exposure does help the metabolism of vitamin-D. It helps you produce it. And if you're in an environment where there's a lot of sun, then you probably don't have a deficiency of vitamin-D, even if you only get small amounts in your diet."

Two trials conclude injections of benralizumab shows promise: "What you have there is a drug that adheres to a protein in the body that limits the inflammatory reaction. It's not approved yet in our country and is undergoing phase three research."

And how exactly would this work? "It's only for patients with rare forms of asthma. A lot of research involves a cell called eosinophil. The eosinophils have globulin in there that when the cell ruptures, the globules stimulate am inflammatory reaction. In stimulating that reaction, we have lining surface cell changes, as well as stimulation of the circular muscles that surround the airwaves themselves. So when those circular muscles contract, we have tightening of the airway, and the airflow through those bronchial tubes becomes limited and that's why patients begin to have shortness of breath. And it's the patients that have a high population of eosinophils that this medicine works best against. It's a medicine that works for up to three months after you receive an injection from it, so it's very promising, but it's not first-line therapy."

In both cases, are people trying to come up with something to reduce inflammation? "Yes, because I think there is a global market for asthmatic patients. And even though less than one percent have severe asthma, at least 25 to 30 percent actually have levels of eosinophils. So if we're able to block it, that is a treatment modality for them."

Are there effective treatments for them now? "Yes. That's why this particular drug is of interest, because those patients that have severe asthma do not respond well to the standard treatment as it exists. Some of the medicine that we give them now are medicines designed to relax the smooth muscle, it does that. There are other medicines designed to reduce inflammation in the airway and mucus secretion, but sometimes that's not enough."
What is asthma? Asthma: Conditions and Treatments

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Two New Possible Treatments For Severe Asthma

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Some of the 24 million people in the U.S. with asthma, or inflammation that narrows the airways, suffer severe symptoms: Like persistent shortness of breath. The inability to speak in full sentences. Or a chest that feels closed. Two new studies tout possible new treatments for severe asthma.

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protein secretion reduced inflammation in mice

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The number of Americans with asthma is rising every year, highlighting the need for new treatments for the respiratory condition. Now, a new study reveals how the quest for new asthma treatments may have been given a helping hand by an unlikely foe: the hookworm.

Researchers say a protein secreted by hookworms could lead to new treatments for asthma.
Image credit: JCU

Hookworms are intestinal parasites responsible for up to 760 million infections across the globe.

While most people infected with hookworm have no symptoms, some people may experience abdominal pain, diarrhea, loss of appetite, weight loss, fatigue, and anemia.

But according to researchers from James Cook University (JCU) in Australia, hookworms may not be all bad.

Study co-author Dr. Severine Navarro, of the Australian Institute of Tropical Health and Medicine at JCU, and colleagues reveal how a protein secreted by hookworms - anti-inflammatory protein 2 (AIP-2) - curbed airway inflammation in a mouse model of asthma.

The study builds on previous research from the team, which showed that the same protein may be effective for an array of inflammatory conditions, including inflammatory bowel diseases (IBD), such as Crohn's disease.

"After our initial success with IBD, asthma was our next logical goal," says Dr. Navarro. "Although IBD and asthma are very different conditions, what they have in common is a defect in the regulation of the immune system, which results in overwhelming inflammatory processes."

Worm protein suppressed airway inflammation in asthma mouse models

For their latest study - published in the journal Science Translational Medicine - Dr. Navarro tested the AIP-2 protein on mouse models of asthma.

"[...] we used a recombinant form of AIP-2, which is to say we're now able to produce it in large quantities," notes study co-author Prof. Alex Loukas, head of the Centre for Biodiscovery and Molecular Development of Therapeutics at JCU.

The team administered the protein to the mice intranasally and through injection, before exposing them to an allergen to trigger the inflammatory response associated with asthma.

The researchers found that AIP-2 suppressed airway inflammation in the mouse models, likely by altering the inflammatory properties of T cells - white blood cells that help fight viruses - in response to the allergen.

"Our previous work on inflammatory bowel disease established that hookworm proteins can change T cells from pro-inflammatory to anti-inflammatory," explains Dr Navarro. "The good news is that this doesn't just protect the gut, it also protects other organs, such as the airways, where asthma develops."

AIP-2 may lead to new treatments for asthma, autoimmune diseases

The researchers also applied recombinant AIP-2 to human cells taken from patients with an allergy to dust mites, which is a common trigger for asthma.

They found that the worm protein curbed activation of dendritic cells - antigen-processing cells - and T cells, an indicator of reduced inflammatory response to allergens.

Asthma now affects around 25 million people in the United States, compared with around 20 million in 2001.

The researchers say their findings may lead to new treatments for asthma, as well as other autoimmune conditions, especially now that they have demonstrated the efficacy of recombinant AIP-2.

"This is an exciting development for us, because it means we're another step closer to being able to put a pill-based treatment into clinical trials, not just for asthma but also for other inflammatory and autoimmune diseases."

Prof. Alex Loukas

Learn how a protein called PD-1 may be an effective drug target for asthma.

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The number of Americans with asthma is rising every year, highlighting the need for new treatments for the respiratory condition. Now, a new study reveals how the quest for new asthma treatments may have been given a helping hand by an unlikely foe: the hookworm.

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Indoor allergen exposure and asthma outcomes. - PubMed - NCBI

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genetic polymorphisms associated with prostate cancer can indicate risk and therefore inform treatments with less risk

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On Tuesday, Ben Stiller posted an essay on the website Medium with the provocative title "The Prostate Cancer Test That Saved My Life," explaining that his doctor started monitoring levels of prostate-specific antigen (PSA) in his blood when he was 46. After a year and a half of "rising PSA numbers," he went for an MRI and biopsy and learned he had a "mid-range aggressive cancer." His prostate was removed, Stiller is now cancer-free, and he continues to rave about the PSA test, appearing on the Howard Stern show and sparking plenty of discussion among celebrity doctors like Dr. Oz.

Problem is, the U.S. Preventative Services Task Force (USPSTF), which issues medical guidelines that are widely followed by doctors, declared in May of 2012 that no man of any age should have the PSA test to screen for prostate cancer unless he has urologic symptoms. The USPSTF's recommendation was partly based on evidence it collected showing that 90% of men with PSA-detected prostate tumors opt for surgery, radiation or hormone therapy. At least 20% of men who are treated with surgery or radiation will have adverse effects such as erectile dysfunction or incontinence. Hormone therapy can also cause ED.

Sometimes, those risks may not be worth taking. Stiller's cancer had a grading of 7 on what's called the Gleason score, a system used to predict how aggressive a prostate tumor will be. A Gleason score of 6 or less indicates a slow-growing tumor, while 8 to 10 signals a more aggressive cancer. A recent study published in the journal Urologic Oncology showed that patients with Gleason scores of 6 or less rarely suffer metastasis, or spreading of their cancer-raising questions about whether those men need to be treated at all.

Stiller's 7 score, determined from an MRI and biopsy, was most definitely in the gray area. This is where the shortcomings of PSA testing become all too evident, leaving many men facing the uncertainty of whether or not they should aggressively treat their tumors, like Stiller did, or continue to watch them, says Lee Ponsky, chief of the division of urologic oncology at University Hospitals Seidman Cancer Center in Cleveland. "One of the challenging parts of prostate cancer is we have options," Ponsky says. "That often creates a huge amount of anxiety for patients."

The good news is that many scientists specializing in urology are working on screening techniques and new technologies that may someday be used to augment PSA testing. The goal is to do a better job predicting which men will benefit from surgery and other aggressive treatments-and who would be better off waiting.

Here are some innovations that may increase the reliability of prostate cancer screening:
Risk calculators
The USPSTF is currently re-evaluating its recommendation against PSA testing, which involves reviewing the medical literature in an effort to answer five questions, including whether the potential harms of prostate cancer screening vary according to factors such as age and family history. The agency is also considering whether a technique known as a "prebiopsy prostate cancer risk calculator," used in conjunction with PSA testing, might do a better job of identifying men who need to be treated than the PSA screen alone.

Among the groups working on such calculators is the University of Texas Health Science Center at San Antonio, which has tested its Prostate Cancer Prevention Trial Risk Calculator on more than 6,500 men. The calculator is designed to aid the decision about whether men should be biopsied based on several factors beyond their PSA scores, including results from a digital rectal exam, family history of prostate cancer, age and race. In 2014, they reported that an updated version of the calculator improved the ability to predict who was most at risk for developing high-grade prostate cancer.
Intelligent MRIs
Another focus of urology research is to improve MRI imaging so physicians can gather more information about a patient's prostate risk before subjecting them to invasive biopsies. At University Hospitals in Cleveland, for example, a team developed a technology called magnetic resonance fingerprinting (MRF), an advanced imaging technique that provides a detailed map of the prostate-clearly separating normal from cancerous tissue so oncologists can better assess how aggressive a tumor is.

They are also incorporating artificial intelligence into MRI imaging, teaching computers to recognize cancer with pathology data from past patients who had their prostates removed. That could make MRI imaging more useful both for diagnosing patients and for guiding biopsies, Ponsky says. "This work to develop new technology will make a major impact in the effort to screen patients with high sensitivity and specificity, but in a cost-effective way," he says.
Improved patient surveillance
The realization that PSA is far from a perfect predictor of prostate cancer risk has sent many scientists on a quest to find better biomarkers. Among those that have been studied are prostate cancer antigen 3 (PCA3), a genetic marker called TMPRSS2-ERG and a number of single nucleotide polymorphisms (SNPs) that are associated with prostate tumors and may help predict risk.

The oncology world is also enthusiastic about the potential for early detection using "circulating tumor cells"-tiny bits of tumor DNA that are cast off into the bloodstream and may be able to be found with a simple blood or urine test. That idea is the basis of Grail, a company that launched in January with $100 million in funding from genetic-sequencing giant Illumina, Bill Gates, Jeff Bezos' Bezos Expeditions and other big-name backers. Grail's goal is to develop a single test for the early detection of many different types of cancer -though getting there will require years of study and tens of thousands of patients.

As for PSA testing, it's not yet clear whether a potential change of heart from the USPSTF or even celebrity endorsements from the likes of Stiller will bring it back in vogue. For now, advises Ponsky, men should consult their doctors for help making decisions about whether to have the test-and what to do if the results aren't black and white.

"I truly believe in the future we will have better ways of screening men. But right now, the PSA is the best we've got," he says. "No task force should be making a decision for all men. Patients should be making these decisions with their physicians."

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Beyond Ben Stiller's Beloved PSA, Prostate Cancer Screening Must Improve

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On Tuesday, Ben Stiller posted an essay on the website Medium with the provocative title "The Prostate Cancer Test That Saved My Life," explaining that his doctor started monitoring levels of prostate-specific antigen (PSA) in his blood when he was 46.

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using knowledge of genetic polymorphism to detect pieces of genetic material in cows known to produce high yield of milk

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To make India's cows yield more milk, the Department of Biotechnology (DBT) has said it will embark on a year-long project to map and analyse the genomes of at least 40 local breeds of cattle. India is the world's largest producer of milk, due partly to importing European cows and cross-breeding them with local varieties as well as a successful decades-long programme to source milk from small farmers via cooperatives. However, the milk productivity of its cattle, ranging from 2-4 kg a day, is much lower than the 25-38 kg a day of cattle in the U.S., Europe or Israel. Officials in the biotechnology department told The Hindu that the National Institute of Animal Biotechnology in Hyderabad - a DBT-funded organisation - would sequence the genetic structure of several strains of cattle and then take steps to ensure that these cattle were bred and popularised.

Largest population

India is home to the largest cattle population (13.1 % of world's cattle population) in the world which constitutes 37.3 % of its total livestock. Several of these varieties have evolved in varied ecological zones while adapting to a harsh native environment, while being a repository of unique genes that may be useful in developing resistance to tropical diseases and external parasites. So far there are 60 local, eight regional trans-boundary and seven international trans-boundary cattle breeds from India, though barely a tenth are maintained for milk production such as Sahiwal, Gir, Rathi and Sindhi, according to an analysis of the genetic diversity in Indian cows by Rekha Sharma and colleagues in the journal BioMed Central Genetics, in June 2015.

'Make use of technology'

"We have usually relied on foreign breeds for our milk production," said Union Science and Technology Minister Harsh Vardhan at a press conference. "We must use technology to improve our local varieties," he said. Having better breeds would help identify the susceptibility of cattle to disease, their resistance to heat and drought and improve economic prospects for small and marginal farmers, he added.

The project is likely to cost Rs. 50 crore to Rs. 60 crore, said an official, and would use the services of private genome-analysis companies. After sequencing, the department hopes to be able to develop a device, called a Single Nucleotide Polymorphism (SNP) -array that can be used to detect pieces of genetic material known to contribute to high yield. "We aren't doing something that hasn't been done before," said Mohammed Aslam, a senior DBT official, "but these chips will make identifying good animals faster."

For its programme, the DBT will also coordinate with institutes of the Indian Council for Agricultural Research, who have institutes that specialise in cattle breeding, to identify appropriate animals. "All other countries have sequenced the genomes of their cattle such as the Holstein Friesian (A Dutch breed known for its yield and also cross-bred with Indian varieties)," said an official, "but we've not done so for our own cattle. We need to sequence about 400 animals at least. After cattle, we'll move on to chicken."

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India to map genes of local cattle breeds to boost milk yield

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To make India's cows yield more milk, the Department of Biotechnology (DBT) has said it will embark on a year-long project to map and analyse the genomes of at least 40 local breeds of cattle.

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Study of the effects of particular genes on the variation in drug response and pharmacogenomics is the study of the effects of the whole genome on drug response.

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Pharmacogenetics is the study of the effects of particular genes on the variation in drug response and pharmacogenomics is the study of the effects of...