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Preference: Immunology and Allergy

411

Candidate profile – Professor Brad Frankum OAM  BMed(Hons) FRACP

Nominating for the position of AMA President

As a consultant physician specialising in immunology and allergy, I divide my time between a fractional staff specialist role at Campbelltown and Camden Hospitals, and my private specialist practice at Narellan NSW.

In addition, I run an immunology and allergy clinic at the Tharawal Aboriginal Medical Service in Campbelltown. I also serve as the Executive Clinical Director of Campbelltown and Camden Hospitals.

I have extensive experience in the university, public hospital, and Medical College sectors, and have been a board member of the Southwest Sydney LHD since its establishment. I have been involved in the teaching and training of thousands of medical students and young doctors.

Fourteen years ago, I realised the importance of ‘being a part of the conversation’.

The Campbelltown and Camden crisis was a lightning rod, and a significant reminder that doctors need to be at the centre of healthcare decisions.

If we fail to be present, and if we allow non-medical professionals to have absolute control over hospitals, patients, and our healthcare system, then we must accept the consequences.

Many factors led to the crisis and looking back we need to heed the conditions that contributed to that situation – there was explosive population growth, a dearth of health funding and resources, and a complete lack of Government support.

When our hospital was accused of poor standards of care and a litany of other failings in the early 2000s, the State Government and the media at the time were only too keen to scapegoat the clinicians in order to deflect from the chronic neglect the whole of the south-west of Sydney had suffered from successive governments and the bureaucracy.

People’s careers were in tatters, and those of us demanding due and fair process were subject to serious intimidation.

It was only with the unwavering support of the AMA that I was able to lead the clinicians to stand up to what amounted to the tyranny of the government at the time.

Out of the mess, and really against the odds, we now have the biggest hospital in NSW at Liverpool, a $632 million upgrade occurring at Campbelltown to grow to a 900-bed facility over the next 10 years, and a very successful medical school at Western Sydney University in its 11th year, producing very fine medical graduates.

This episode taught me the value of the AMA, as well as the importance of standing together as a medical profession to advocate on behalf of doctors, patients and a better healthcare system. It led me to join the Council of AMA (NSW), where I have held numerous positions – most recently serving as President.

The lack of imagination and vision in health policy on both sides of politics should be of great concern to all of us.

The AMA can elevate the debate and promote a vision for health and exert great influence at the next Federal election. At times like these, it is the duty of the AMA to step up and demand more imagination and focus on health from politicians who would prefer to coast along with conditions just tolerable enough so that few complain loudly. We owe it to our members and patients to speak up, because if we don’t no one else will.

In the next AMA Federal Election, I will be running on a ticket with Dr Jill Tomlinson from Victoria for Vice-President. Jill and I will work extremely effectively as a team. Jill will bring a range of skills to the position across a range of issues. She has been a strident voice against harassment, a great supporter of junior doctors, and has great knowledge of the application of digital technology.

I believe that together we can provide a strong voice for the AMA.

* See other candidate profiles on this site. 

 

 

The link between acid suppressants and allergy

 

The evidence is mounting that the dramatic increase in kids’ allergies over the past couple of decades could have something to do with medication-induced disturbances in the intestinal microbiome.

The latest evidence for this hypothesis comes from a large, retrospective US study published this week in JAMA, involving nearly 800,000 children under six months old. The researchers cross-checked the use of H2RA and PPI acid suppressants, as well as antibiotics, with the subsequent diagnosis of allergic diseases in this cohort.

Infants in the cohort who were prescribed acid suppressants were more than twice as likely to develop food allergies in later childhood, with peanut and cow’s milk allergies being the most common. They were also 70-80% more likely to develop an allergy to a medication, and 45-50% more likely to be hospitalised for anaphylaxis. Rates were also higher for allergic rhinitis and asthma.

Infants prescribed antibiotics also had higher allergy rates: they had double the risk of asthma, a 75% greater risk for allergic rhinitis and a 41% higher risk for anaphylaxis.

“Acid-suppressive medications and antibiotics should be used during infancy only in situations of clear clinical benefit,” the researchers conclude.

They caution that as the study was observational, a causal link cannot be demonstrated. But while it is possible acid-suppressants or antibiotics were given for misdiagnosed allergic diseases, the authors say this is very unlikely to explain all the findings.

They say what is more likely is that acid-suppressants or antibiotics enhance the development of allergies by altering the makeup of the microbiome. They point to increasing evidence that healthy flora in the gut modulate immune responses and augment regulatory T-cell populations, possibly by the production of short-chain fatty acids. Getting the right microbial balance in early life seems especially important, with mouse studies showing antibiotic-induced dysbiosis causing allergies in neonatal mice but not in adult mice.

The study showed a stronger risk of food allergies with acid-suppressing drugs than with antibiotics, which might be because the former increases sensitisation to ingested antigens by decreasing protein breakdown in the stomach, the authors say. In addition, H2RAs may have a direct effect on the immune system, as histamine is increasingly recognised as having a role in modulating immune system function.

In current paediatric practice, acid suppressants are generally considered safe and are commonly prescribed for infants who have a regurgitation problem or are fussy. Studies like the current one may prompt a rethink in prescribing patterns, particularly given that gastric regurgitation in infants is not a disease but a developmentally normal process.

Recent research has found little clinical benefit in the use of H2RAs and PPIs in infants, and paediatricians are increasingly advising against overprescription of these drugs. They should be prescribed “only in situations of clear benefit”, the study authors warn.

You can access the full study here.

Be cautious about fad gluten free diets

Researchers from the University of Newcastle (UON) have highlighted potential risks of following a gluten-free diet, urging the community to only drastically change their eating habits if formally diagnosed with coeliac disease.

Led by Dr Michael Potter from the Hunter Medical Research Institute, a new narrative review published in the Medical Journal of Australia stresses the adverse effects of changing to a gluten-free diet after a self-diagnosis.

Aside from being more expensive and often challenging in a social setting, there is evidence a gluten-free diet can adversely affect human health.

The study found a gluten free diet may negatively affect cardiovascular risk factors such as total cholesterol levels, weight gain leading to obesity, glucose intolerance and blood pressure.

UON researchers say their report raises concerns about self-diagnosis for gluten intolerance with those who incorrectly attribute adverse physiological symptoms to wheat ingestion and unnecessarily subject themselves to a gluten-free diet.

Research found that of people self-reporting gluten or wheat sensitivity, only about 16 per cent show symptoms when subjected to a clinical trial to replicate the response.

The UON research is supported by a recent American study that found evidence unnecessarily following a gluten-free diet could place you at a higher risk of developing Type 2 diabetes.

In a study conducted by the American Heart Association over the span of 30 years, researchers found that out of those eating 12 grams or less of gluten per day, the ones who ate most gluten had a lower Type 2 diabetes risk.

The American Heart Association believes that gluten-free diets have become popular for people without these conditions, though there is lack of evidence that reducing gluten consumption benefits long-term health.

“Gluten-free foods often have less dietary fiber and other micronutrients (such as vitamins and minerals), making them less nutritious, and they also tend to cost more,” said Dr Geng Zong, a Research Fellow at Harvard School of Public Health.

“People without celiac disease may reconsider limiting their gluten intake for chronic disease prevention, especially for diabetes.”

Coeliac Australia estimates that one in 70 Australians have coeliac disease, but 80 per cent are undiagnosed and symptoms of coeliac disease vary considerably.

Coeliac Australia warns there are a number of tests and treatments for allergy, intolerance and coeliac disease that are used in the absence of any scientific rationale. These tests and treatments have been shown to be unreliable when subjected to careful study.

Unproven testing methods for coeliac disease provide misleading results, delay correct diagnosis and lead to unnecessary and ineffective treatment cautions Coeliac Australia.

MEREDITH HORNE

The new hypothesis that is revolutionising medicine

 

Inflammation has lately become one of the hottest topics in current medical research. Last month, a breakthrough trial presented at the congress of the European Society of Cardiology looks like putting the so-called ‘inflammation hypothesis’ in chronic disease firmly on the map.

The US-based CANTOS trial randomised 10,000 patients who had already survived a myocardial infarction to a drug called canakinumab, which targets the inflammatory pathway interleukin-1 beta but does not affect cholesterol levels. The researchers found a 15% reduction in the risk of myocardial infarction or stroke, and a 30% reduction in the need for a major intervention such as angioplasty or bypass surgery, compared with usual treatment.

The trial won’t be changing clinical practice in heart disease any time soon, not least because canakinumab is a phenomenally expensive drug, and one that also has complex side effects. But the results are nonetheless hugely important, because for the first time researchers have found hard evidence for the role of inflammation in chronic heart disease, independent of lipid levels.

The principal investigator Dr Paul Ridker, a cardiologist at the Brigham and Women’s Hospital in Boston, said the findings have far-reaching implications.

“It tells us that by leveraging an entirely new way to treat patients – targeting inflammation – we may be able to significantly improve outcomes for certain very high-risk populations”.

Another fascinating finding from the study was a substantial reduction in the incidence of lung disease in patients randomised to canakinumab, suggesting that inflammation may play a role in cancer growth as well.

This finding, Dr Ridker said, will “turn the way people look at oncology upside down”.

Heart disease and cancer are hardly the only areas where researchers are looking at how reducing inflammation might reduce risk. Diabetes, HIV, neurodegenerative diseases such as Alzheimer’s or multiple sclerosis, and even depression have been the subject of research.

A study published just this month looks at how inflammation may be implicated in the pathogenesis of Alzheimer’s disease. The brains of people with Alzheimer’s typically have abnormal deposits of two proteins, amyloid beta and tau. US researchers from the University of North Carolina have shown in cell cultures how accumulation of amyloid beta can trigger an inflammatory response, which in turn damages neurons. The type of neuronal damage leads to the formation of bead-like structures containing abnormal tau protein; similar structures as these are found in the brains of people with Alzheimer’s.

Another study has shown that people with fattier, more pro-inflammatory diets tend to have smaller brain volumes and worse cognition.

Brain inflammation may also play a role in depression, according to several recent studies which found high levels of inflammatory markers in the brains of people suffering from the condition. A trial is currently enrolling to trial a biologic called sirukumab for people with major depressive disorder. This drug was initially developed to treat people with rheumatoid arthritis, but when it was trialled in that area, researchers found an interesting side-effect: patients randomised to sirukumab reported having improved moods and less depression.

Targeting inflammatory pathways in the immune system is clearly a promising avenue for drug development, but it’s far from straightforward: dampening the immune response can have dangerous consequences and can promote infection.

For example, sirukumab, the drug being trialled for depression, was recently knocked back by the FDA as a treatment for rheumatoid arthritis, as it had been implicated in several deaths from serious infection and heart disease. Similarly, in the CANTOS trial for heart disease, several deaths from serious infection were reported with canakinumab.

Dr Ridker, the lead researcher on the CANTOS trial, is now enrolling for a second trial, this time testing the anti-inflammatory effects of the immunosupressive drug methotrexate, which has long been used in the treatment of rheumatoid arthritis and whose safety profile is well understood.

Patients will be tracked not only to see if methotrexate lowers risk of cardiovascular events, but also if it reduces cancers. Time will tell, but one thing is certain: the “inflammation hypothesis” is now very much a fixture in the medical research firmament.

[Perspectives] Gerd Burmester: enduring leader in rheumatoid arthritis

Having been Professor of Medicine at Berlin’s Charité University Clinic for the past 23 years, Gerd Burmester is among the university’s longest-standing full professors. He leads a 100-strong Department of Rheumatology and Clinical Immunology, and is as committed to research in the laboratory as to work in the clinic. His team is collectively researching how to reprogramme the human immune system, with an emphasis on the molecular pathways that underpin autoimmunity across many diseases, but especially in rheumatoid arthritis (RA).

[Series] Strategies for long-term preservation of kidney graft function

Kidney transplantation has become a routine procedure in the treatment of patients with kidney failure, and requires collaboration of experts from different disciplines, such as nephrology, surgery, immunology, pathology, infectious disease medicine, cardiology, and oncology. Grafts can be obtained from deceased or living donors, with different logistical requirements and implications for long-term graft patency. 1-year graft survival rates are greater than 95% in many centres but improvement of long-term function remains a challenge.

News briefs

Antiretroviral therapy gives patients with HIV infection 10 more years

Life expectancy of 20-year-old patients starting treatment for HIV has increased by about a decade in the European Union and North America since the introduction of antiretroviral therapy in the mid-1990s, according to research published in The Lancet HIV. The authors, from the University of Bristol, proposed that their findings could reduce stigmatisation and help people with HIV infection gain employment and obtain medical insurance, as well as encouraging diagnosed patients to start treatment as soon as possible. Their projections indicate that the life expectancy of a typical 20-year-old patient who began treatment since 2008 and had a low viral load after a year of treatment may approach that of the general population (about 78 years). The study analysed data from 18 EU and North American studies for 88 504 people with HIV infection who started antiretroviral treatment between 1996 and 2010. It tracked how many people died during the first 3 years of their treatment, their cause of death, HIV viral load, immune cell (CD4) count and whether they were infected through injecting drugs. Fewer people who started treatment between 2008 and 2010 died during the first 3 years of treatment than those who started treatment between 1996 and 2007. The number of deaths during treatment directly attributable to AIDS declined between 1996 and 2010, probably the result of newer drugs being more effective in restoring immune function. Measures of HIV also improved, with the average CD4 cell count after a year of treatment increasing from 370 cells per microlitre of blood in 1996–1999 to 430 cells per microlitre in 2008–2010, while the proportion of people with a low HIV viral load increased from 71% to 93%. Between 1996 and 2013, the life expectancy of 20-year-old patients treated for HIV infection increased by 9 years for women and 10 years for men in the EU and North America. Projections based on death rates in the second and third year of treatment for Europeans and North Americans estimated that 20-year-old men and women starting therapy between 2008 and 2010 who survived the first year of treatment would live to 73 and 76 years respectively.

http://dx.doi.org/10.1016/S2352-3018(17)30086-3

Untethered proteins found in MKD

Researchers from the Garvan Institute of Medical Research in Sydney have shown that a family of untethered proteins builds up in the cells of children with a rare genetic condition, mevalonate kinase deficiency (MKD). Individuals with MKD experience repeated and frequent inflammatory febrile episodes that last for days and are accompanied by hepatosplenomegaly, lymphadenopathy, arthralgia, and skin rash. These febrile crises are similar to those associated with hyperimmunoglobulinemia D and periodic fever syndrome. The attacks usually begin in infancy and continue throughout life, although they are most frequent in children. In blood cells from people with MKD, the investigators found that several intracellular proteins from the same family (Rab proteins) had no isoprenoid tail. Much like a child holding the string of a balloon, an isoprenoid tail is thought to act as a molecular tether for the protein to which it is attached. The isoprenoid tails on Rab proteins keep them close to the cell membrane; without their tethers, the Rab proteins, and other related proteins, are free to move into other parts of the cell. It is thought that this could initiate the disease process in MKD, triggering inflammation. The researchers found that untethered Rab proteins are found only in people in MKD, and not other rare diseases that have similar clinical symptoms (the periodic fever syndromes) or in the parents of children with MKD. These findings, published in the Journal of Allergy and Clinical Immunology, pinpoint a key feature of MKD that could be used to fast-track diagnosis of the disease, a process that is often difficult and protracted.

http://dx.doi.org/10.1016/j.jaci.2017.02.033

Resistance exercise could be a new ‘prescription’

A new study by Griffith University’s Menzies Health Institute Queensland has linked resistance exercise with boosting you immune system and aiding in injury health.

Until this study was undertaken, little was known about the impact of resistance exercise.

Published in Immunology Letters, the researchers examined 16 previous studies undertaken during1989-2016 that investigated participants undertaking a single session of resistance exercise encompassing various exercises.

“We combined the data from all relevant scientific publications, including two of our own original articles, to conduct a stringent systematic analysis of the resistance exercise research,” said Dr Adam Szlezak from Griffith’s Menzies Health Institute Queensland.

The study found that both high and low dosages of resistance exercise increased the immune system’s surveillance potential in the participants in a similar way to that of aerobic exercise, much like drugs can.

“We found that both high and low dosages of resistance exercise increased the immune system’s surveillance potential in the participants in a similar way to that of aerobic exercise. Even a low dose of thumb resistance exercise increased the number of key white blood cells in the circulation,” Dr Szlezak said.

The research suggested that resistance exercise appears to improve immuno-surveillance similar to that of moderate intensity aerobic exercise, regular moderate intensity 20-45 min work-outs in the gym may provide similar protection against upper respiratory tract infections (URTI).

Now that we know that different resistance exercise doses can result in distinct biological responses, much like drugs can, we now need to see if these responses can be used to reduce risk of URTI, as well as improve recovery from illness and injury, said Dr Szlezak.

The research also suggests that GPs should recommend that their patients abstain from all forms of exercise in the hours prior to blood collection for requesting full blood counts due to its impact on white cell count.

Meredith Horne

News briefs

Hidden risk population for thunderstorm asthma

Research presented at the Thoracic Society for Australia and New Zealand (TSANZ) Annual Scientific Meeting in Canberra last month identified “a potentially hidden and significant population susceptible to thunderstorm asthma”. “This is a wake-up call for all of Australia, but particularly Victoria as it prepares for its next pollen season,” said Professor Peter Gibson, president of TSANZ. “Many more people than previously thought are at risk of sudden, unforeseen asthma attack. It is essential that we invest more research into this phenomenon and educate our health services and public to take preventative and preparedness measures.” Nine people died in Victoria late last year and over 8500 required emergency hospital care when a freak weather event combining high pollen count with hot winds and sudden downpour led to the release of thousands of tiny allergen particles triggering sudden and severe asthma attacks. Those most seriously affected were people who were unaware they were at risk of asthma and therefore had no medication to hand. In the study of over 500 health care workers, led by the Department of Respiratory and Sleep Medicine, Eastern Health, Victoria, almost half the respondents with asthma experienced symptoms during the thunderstorm event. Most took their own treatment, a few sought medical attention and one was hospitalised. More alarming was the 37% of respondents with no prior history of asthma who reported symptoms such as hayfever, shortness of breath, cough, chest tightness and wheeze during the storms. The study also found that people with a history of sensitivity to environmental aeroallergens (eg, ryegrass or mould) were far more likely to report symptoms than those with a history of either no allergy or allergy to dust mite/cats. Physical location, described as predominantly indoors versus outdoors, was not a risk factor. “This study gives us an indication of the proportion of our population that might be at risk of thunderstorm asthma, but are unaware of it as they have no history of asthma. It also suggests that a history of hayfever is one of the greatest risk factors,” said lead researcher Dr Daniel Clayton-Chubb. “The key message from our work is that anyone with hayfever should ensure that they have ready access to quick-acting asthma treatments such as bronchodilators at all times, but particularly in pollen season or if thunderstorms are predicted. Severe thunderstorm asthma symptoms can strike rapidly and without warning.”

New genetic causes of ovarian cancer identified

A major international collaboration has identified new genetic drivers of ovarian cancer, findings which have been published in Nature Genetics. The study involved 418 researchers from both the Ovarian Cancer Association Consortium, led by Dr Andrew Berchuck from the United States, and the Consortium of Investigators of Modifiers of BRCA1/2, led by Professor Georgia Chenevix-Trench from QIMR Berghofer Medical Research Institute. Professor Chenevix-Trench said it was known that a woman’s genetic make-up accounts for about one-third of her overall risk of developing ovarian cancer. “This is the inherited component of the disease risk,” Professor Chenevix-Trench said. “Inherited faults in genes such as BRCA1 and BRCA2 account for about 40% of that genetic risk. Other variants that are more common in the population (carried by more than one in 100 people) are believed to account for most of the rest of the inherited component of risk. We’re less certain of environmental factors that increase the risk, but we do know that several factors reduce the risk of ovarian cancer, including taking the oral contraceptive pill, having your tubes tied and having children. In this study, we trawled through the DNA of nearly 100 000 people, including patients with the most common types of ovarian cancer and healthy controls. We have identified 12 new genetic variants that increase a woman’s risk of developing the cancer. We have also confirmed that 18 variants that had been previously identified do increase the risk. As a result of this study, we now know about a total of 30 genetic variants in addition to BRCA1 and BRCA2 that increase a woman’s risk of developing ovarian cancer. Together, these 30 variants account for another 6.5% of the genetic component of ovarian cancer risk.”