Thursday, 31 October 2013

Causes of chronic allergies

Allergic bronchopulmonary aspergillosis (ABPA) is a potential complication in asthmatic people, and can potentially lead to chronic pulmonary aspergillosis (CPA) when left untreated. Only recently have global incidences been estimated, with potentially 4.8 million people affected worldwide. (Denning et al., 2013)

There is a great quantity of on-going research into asthma and associated allergies, but how do such allergies begin? In recent years scientists have made large strides towards discovering how our immune systems malfunction—ultimately attacking substances which are not harmful. The science behind those mechanisms is complex, involving multitudes of small molecules which play individual roles in various allergic diseases.

There is a strong familial link to allergies; if one parent has an allergy, the child will acquire an allergy in 33% of cases. If both parents have an allergy, that risk doubles to around 70%. Similarly, identical twins have the same allergies in 70% of cases, further corroborating the familial link. It appears that children inherit the likelihood of developing an allergy; however, it is not always the same allergy which occurs in the parent(s). For example, a parent with a peanut allergy may not necessarily pass that specific vulnerability to peanuts to their children.

A number of theories exist attempting to explain why allergies initially occur (i.e. why the body’s immune cells decide to attack a particular allergen). These theories range from genetic to environmental, but there is no conclusive mechanism.

Nevertheless, the processes leading to allergic disease can be described more simply under two stages: sensitisation to an allergen (something which initiates an allergic response), and activation (the process by which the body responds to that allergen). The first stage, sensitisation, can occur with no symptoms, acting as a priming mechanism behind the disease, with no consequences on its own until your body encounters the same allergen again.

During re-exposure, antibodies developed during the sensitisation stage ‘recognise’ the allergen, triggering a cascading immune response. This is the same mechanism which protects us from colds and infections we've previously had, but happening against something non-infectious. This is the reason that allergies and colds have similar symptoms: runny nose, fatigue and sneezing, to name a few.

Tuesday, 29 October 2013

World Medical Association adopts statement on fungal disease diagnosis and management

At their 64th General Assembly in Brazil, the World Medical Association adopted a statement on Fungal Disease Diagnosis and Management’.The statement reads:
“The WMA stresses the need to support the diagnosis and management of fungal diseases and urges national
Professor Arnaldo
governments to ensure that both diagnostic tests and antifungal therapies are available for their populations. Depending on the prevalence of fungal diseases and their underlying conditions, specific antigen testing or microscopy and culture are essential. These tests, and personnel trained to administer and interpret the tests, should be available in all countries where systemic fungal infections occur. This will likely include developing at least one diagnostic centre of excellence with a sufficient staff of trained diagnostic personnel. Monitoring for antifungal toxicities should be available.
Physicians will be the first point of contact for most patients with a fungal infection and should be sufficiently educated about the topic in order to ensure an effective diagnostic approach.
The proposal to the WMA was prepared by Professor Arnaldo from Sao Paulo who commented: “This is the first time that the World Medical Association had considered the size and severity of the problem of fungal disease. Their proposal to ensure that essential diagnostic tests done by trained personnel in all countries is critical to ensuring better patient care.”

Thursday, 24 October 2013

Support Patients Research Group at North West Lung Centre (Home of the National Aspergillosis Centre)

Support Danielle Yuill's project to set up a group of patients (& carers) to assist with research at the North West Lung Centre and National Aspergillosis Centre, Manchester, UK. Danielle has organised a meeting in Manchester to begin with. People from other parts of the UK & world might also be useful - those who cannot make the meeting this Saturday could send an email.

For a full explanation of the project see our last Patients Support Meeting

Danielle's appeal for help:

Join me… Saturday 26th October Britannia Country House Hotel Palatine Road Didsbury, Manchester 12.30 till 2.30pm Lunch and refreshments provided. We are able to offer you a payment of £25.00 for taking part and will also reimburse your travel expenses.

Contact details Danielle Yuill Clinical Project Manager Tel. 0161 291 5906 (Mon-Tue) 0161 291 5031 (Wed-Thu) Email.

Monday, 21 October 2013

Fungal infections pose a significant threat to the health of our plants and animals and ecosystem

At  the recent 6th Trends in Medical Mycology conference held in Copenhagen, Dr Fisher presented a significant case that fungi are emerging as a serious threat to both animal and plant health and to the health of the ecosystem worldwide.
The fungal kingdom is incredibly diverse with an estimated 1.5 million species but probably 500 times more may exist.
Amphibian chytridiomycosis

Whilst we use fungi to our benefit in a variety of ways - from drug development to food production - emerging infectious fungi nevertheless represent a serious threat to the Earth's ecosystem. Several animals species, including various amphibians, bats, honeybees and snakes, have been the victims of pandemic fungal diseases and this threat appears to be widespread amongst animals including turtles (Fusarium solani) and corals(Aspergillus sydowii).
Many types of fungi can cause life threatening infections in humans and related hospital admissions are rising. Plants are not exempt from the fungal attack- they represent a serious threat to plant health worldwide. Here in the UK, Chalara fraxinea (Hymenoscyphus pseudoalbidus), or ash dieback is spreading through our ash tree population like wildfire, having destroyed over 100,000 ash trees since discovery of the disease in 2012. Global disease alerts show that fungal alerts are increasing in relation to other pathogenic causes; and fungi have become the highest threat to extinction (by infection) in both animal (72% of extinctions)  and  plant (64% of extinctions) species. Alarmingly this threat is increasing with time. The bat species Myotis lucifugus  is almost certain to become extinct in just over a decade as the Pseudogymnoascus destructans fungi spreads.

Humans are spreading the problem by transportation - accidentally and  commercially, but evidence (Bebber et al 2013) now shows that climate change is enhancing the spread of fungi - by allowing establishment in previously unsuitable locations. They report a shift in distribution of many pathogens (since 1960) as measured by a poleward shift annually since that time, of many pathogens including fungi. The distribution of some other taxonomic groups such as nematodes have shifted away from the poles.

These increasing trends represent a threat, in both the short and long term, to human, animal and plant health. The high socio-economic cost to crops and healthcare provide good impetus for further research, as the battle is not one which we can afford to lose.

(Fisher, M et al . (2013) Emerging fungal threats to animal, plant and ecosystem health. Presented at the 6th Trends in Medical Mycology, Copenhagen, Denmark: Presentation) view

Tuesday, 15 October 2013

Pcovery wins funding to improve fungal treatment options

As previously reported on this blog, the options available to clinicians treating fungal infections are narrow. As a whole, the pharmaceutical market is reluctant to invest heavily in developing new antifungal medication because of the comparatively small (though still extensive) market.

Clinicians and patients may find some happiness in the recent news that the Wellcome Trust has awarded £3.7 million in funding to Pcovery, a Danish biotechnology company aiming to break into the antifungal drug market. The company is currently identifying lead target compounds before moving on to pre-clinical drug trials.

Pcovery CEO, Casper Tind Hansen, expressed his delight at the news: "The generous funding is an acknowledgement of our work, and the money allows us to focus on developing a novel compound to treat invasive fungal infections. We now have a team of the right competences, and access to world class expertise within anti-fungal drug development."

"We have set up an ambitious and well-structured plan to come up with a novel treatment of invasive fungal infections, which will hopefully help this group of severely sick patients."

(Pcovery website)

Friday, 11 October 2013

Cardiotoxicity of antifungal drugs

The treatment of fungal disease is significantly hampered by the unavailability of new antifungal drugs, and increasing resistance towards registered antifungals such as the triazoles. With the introduction of the echinocandin class of antifungals (Caspofungin (Merck) in 2001, followed shortly by Micafungin (Astellas) and Anidulafungin in 2005 and 2006 respectively), the situation has improved but not resolved. There is still a widespread shortfall of antifungal treatment options.

Of the drugs currently available, cardiotoxicity appears to be a side effect in some patients with pre-existing cardiac disease. Some traditional antifungal drugs, such as the polyene amphoteracin B (AmB) have been associated with reduced cardiac function. Other examples include itraconazole, which has been implicated in heart failure in some patients, and voriconazole, which has been linked with Torsades de pointes -- an electrical disturbance in the heart which, left untreated, can lead to fatal heart disease.

A study into echinocandin cardiotoxicity by Stover et al. (2013) has shown that rat hearts treated with Anidulafungin and Caspofungin display reduced function, including at doses similar to that in humans after administration. Notably, and interestingly, Micafungin was not associated with statistically significant changes in this study, which coincides with the fact that there are no adverse cardiac events noted with patients taking Micafungin. On the other hand, Caspofungin and Anidulafungin have both been reported, with the former being responsible for sudden cardiac death in one patient and the latter being responsible for a case of flash pulmonary oedema.

The current advice to clinicians at the moment is to monitor all patients with pre-existing cardiac disease who are on AmB or triazole antifungals. More research is needed into the potential cardiotoxicity of echinocandin drugs in patients with pre-existing cardiac disease.

Thursday, 10 October 2013

Improving active and healthy aging

In late 2012, MEPs met to discuss the impact of early diagnosis and control on those with chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD)—projected to become the third leading cause of death by 2030 worldwide. Other chronic respiratory illnesses face similarly large increases in prevalence over the coming decades, including asthma, allergic rhinitis and allergic bronchopulmonary aspergillosis (ABPA).

One issue raised at the meeting was the role of patients' organisations in the fight against chronic respiratory disease. Patients are generally not well placed to campaign directly for improvement to public health initiatives, and it's vital that non-profit organisations can rally on their behalf. As part of the Aspergillus website, we run a patient's website which links in directly to patients at the National Aspergillosis Centre and elsewhere.

The final aim is to improve active and healthy ageing (AHA). This can be achieved through prioritised research, particularly tackling at-risk groups such as children. Since children with asthma are at a higher risk of developing COPD when older, improvements to future clinical and scientific research disciplines is vital to help develop novel therapies for this risk group.

Tuesday, 8 October 2013

The digital media age

Last year Amazon and Waterstones announced that, for the first time in history, electronic book sales eclipsed printed book sales for the first time. It is reasonably safe to assume this is an ongoing trend—engineered by the increased use of the internet in our everyday lives—and hence this finding is unlikely to reverse soon, if ever. Does that, then, point to the demise of the printed book?

On the face of it, it seems a straightforward conclusion. If a book provides no additional benefit to it's reader, and the needs of that reader can be met equally and more efficiently with another commensurate medium, what purpose does such a book serve? Medical journals are moving faster than ever into the digital age; whilst some preserve printed copies for monthly subscribers, most at least publish a digital equivalent and, increasingly, journals are moving to a digital-only subscription model.

It's not quite a done fight just yet, however. There is a particular aesthetic benefit that conveys an advantage to printed books; owners become more attached to printed books than they do to ebooks. Heritage and style are less emphatic read as a PDF compared with the distinct smelling, aging books.

Does that negate from the fact that ebooks are cheaper, more accessible and transportable than their printed versions? Not at all, but for many people those attributes are not essential but optional.

Monday, 7 October 2013

Evidence-based... funding?

White HouseSince the US Government shutdown is on-going, with an impasse between the House and Senate revolving around 'Obamacare', it seems pertinent to discuss how health care services should be funded (or indeed cut). Several Western governments, including the US and the UK, routinely create vast expenses that exceed their incomes, leading to a budgetary crisis similar to the current one. The temptation for governments is to slash funding to the fiscally more 'greedy' programmes; in essence, to force reductions in expenditure in those areas, hoping they adapt to the new fiscal pressure.

It has been suggested, as an article written in the Nature journal back in April discusses, that a more sensible approach is t o allocate funds based upon evidence; that is, to fund what is proven to work, and cut what funding to failed initiatives. In fact it appears as though the US government is taking this route in order to fund all programmes within the sciences. From the April budget, it is made clear all branches need to follow six core practices:

  1. Goal-setting;
  2. Frequent measurement of performance and other indicators;
  3. On-going analysis;
  4. Use of evidence in decision-making;
  5. Data-driven reviews; and
  6. Information dissemination that is timely, accessible, and user-friendly.
One method, currently being trialled for teen pregnancy prevention in the US, is a tiered funding approach which is not dissimilar to the phases in clinical trials. At the lower stages there is initial funding to explore and assess ideas and developments, but that funding is limited. To progress through the tiers, and hence receive more funding, one would need to acquire more evidence to support the case for development.

Another method, more commonly used here in the UK, is through the use of social impact bonds (better known by the term 'Pay for Success'). This is particularly relevant under the increasing privatisation of medical services; outsider investors are required to meet set targets and prove they are saving the public money in order to receive compensation from the NHS. 

Wednesday, 2 October 2013

Isavuconazole Shows Promise for Invasive Aspergillosis

The Wall Street Journal have reported that Astellas, developer of a new antifungal drug isavuconazole, have published some results from their phase III trials on the treatment of invasive aspergillosis that show its promise in comparison to voriconazole.

 In particular in a sample of 500 patients there was 7% lower mortality and only 40% drug related adverse events with isavuconazole versus 60% drug related adverse events for voriconazole, so there may well be advantages to using isavuconazole for the treatment of invasive aspergillosis as although there is little difference in mortality there may be fewer side effects for the patient. NB significant numbers of patients have to stop taking voriconazole due to excessive side effects.

Overall effectiveness at the end of the study (42 days) was comparable and certainly no worse than using voriconazole - so effectively we can conclude isavuconazole is no worse in terms of outcome for the patient and may well cause fewer adverse events so may be tolerable by more patients.

Wall Street Journal report

Tuesday, 1 October 2013

Better Healthcare: What Does the World Want Most? Why Does the US Want More?

The United Nations are currently running a survey in 194 countries of the world to ask what we all want most from future development. There were 16 options offered and contributors could choose 6 from the list.

These are the overall results so far

We can see that overall the desire for better healthcare is the second highest priority around the world, whereas the desire to take action on climate change is the least most important.

Interestingly the desire for better healthcare is not consistent from country to country. In the UK it is our 8th priority and this is consistent with UK being a more highly developed country thus we can spend more on our health services, presumably generating better services - the situation is the same in similar countries. Perhaps we are happier with our health services relative to other priorities, perhaps we are have more leisure and thus have time to consider other priorities whereas poorer countries have to concentrate on living! 

There is however one exception to this rule. If we take a look at the amount each country spends on healthcare and correlate it to the number of people in that country who profess a desire for better healthcare we get this table:

We can see a reasonable correlation (the red line) between health spend and desire for better healthcare - the more we spend the less the desire. The exception is the US - it spends nearly 3x the UK, 4x that of Czech Republic but has more people asking for a better health service and occupies a spot well above the red line. Why?

We know that the US system is based on insurance and tends to be more expensive to run - but other countries have largely private health systems and spend much less. Perhaps ironically as today marks the beginning of the partial shutdown of US public services because one political party are blocking the introduction of a policy that would give a measure of healthcare to everyone in the US, one possible explanation is that 17% (50 million people) of the population of the US have minimal healthcare - a third world population in a first world country in terms of healthcare.

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