Wednesday, 23 February 2011

Voriconazole therapy and flouride toxicity

Patients who are in receipt of a transplant are known to be vulnerable to infection by Aspergillus as part of their post operative regimen includes immune-suppressive drugs to combat rejection of the transplanted organ. Suppression of the immune system to prevent rejection also leaves the patients more vulnerable to infections of all kinds, some of the most difficult to treat infections are fungal infections such as aspergillosis. For this reason transplant patients are often started off on an immune-suppressive regimen that is quite powerful but that regimen is tapered down to the point at which there is still no rejection of the transplanted organ, but the patients' immune system can recover enough to fight infection.

The authors of this paper describe a patient on long term treatment with voriconazole, required after aspergillosis complicated her heart transplant.  That treatment seems to have been successful but 4 years later she was still taking voriconazole, presumably to prevent the fungus reappearing.
Unfortunately the patient was suffering from bony outgrowths in several parts of her body (see picture).

Tests revealed very high levels of flouride in her bones, but there was no evidence that there was any excessive intake of flouride in her diet e.g. flouride containing medications, excessive black tea consumpton, swallowing toothpaste.

The voriconazole molecule contains 3 flouride atoms so it was discontinued and replaced with itraconazole. Within 3 months the patient's symptoms and clinical signs had improved dramatically.

This is the first suggestion that voriconazole may cause flouride toxicity, so the authors of the paper decided to test the theory that voriconazole was causing this problem. 20 post transplant patients were recruited and consented to having their voriconazole and flouride levels tested. 5 patients receiving voriconazole started to develop bony outgrowths (periostitis) and all recovered within 3 months of stopping voriconazole therapy.

We can conclude that there is reason to suspect that voriconazole is causing flouride toxicity in some patients. This study was small so we cannot positively conclude that this is the case but there is enough to decide that awareness and vigilance of this possibility amongst transplant patients taking long term voriconazole therapy is desirable and necessary.

Tuesday, 15 February 2011

Long term marijuana smoking - a link to chronic pulmonary aspergillosis (CPA)?

Marijuana (cannabis) is the most frequently used illicit substance in many western countries - although it is a class B drug. A link between schizophrenia and cannabis use is well known - but effects on the lung and possible cancer are complicated by the fact that smoking of tobacco alone can cause cancer.
Both tobacco and marijuana are commonly contaminated with fungi and aspergillus - antibodies to aspergillus in blood samples from marijuana smokers do occur. It is uncertain whether the exposure to aspergillus comes from handling the marijuana or from inhaling spores which may survive the burning process.

A recent publication has described 2 cases of chronic pulmonary aspergillosis associated with extensive medicinal use of marijuana (Gargani et al 2011).
One patient aged 47 was already a heavy smoker but his breathlessness was considerably worse once he commenced marijuana smoking (5 joints per day), for relief of rheumatoid arthritis. He was coughing up thick mucous and noticed unusual weight loss.
His lungs contained a number of bullae - these are like air filled holes in the lung tissue - he had surgery removing part of his lung and one bullae was found to contain an aspergilloma 7 cm across. After surgery his lung function did not improve and and the other lung was seen to contain a number of these bullae or "holes". After antifungal treatment for 4 months with posaconazole his cough and sputum production improved, he also stopped using marijuana. He was monitored for 4 years and showed no recurrence of symptoms.

The second patient had smoked around 20 joints a day from the age of 10 - initially for pain relief. At 35 he was diagnosed with emphysema but at 43 years old - he suffered respiratory failure - he gave up cannabis smoking aged 44- but by this time he needed long term oxygen therapy and could only walk 10 metres on the flat. Radiology of his lungs showed complex cavitary lesions and a probable aspergilloma. Sputum samples revealed the presence of Aspergillus fumigatus with positive antibody tests - all consistent with CPA. His lungs deteriorated so much he needed a lung transplant - but the presence of Aspergillus was a contraindication to a lung transplant. He was given antifungal treatment but died within a few months.

Marijuana usage has been implicated in some cases of Aspergillus infections -but evidence from these 2 patients indicates that development of aspergilloma and CPA may also be linked to smoking this substance.
The method of smoking marijuana is different to tobacco - usually there is no filter, the breathe is held for longer, exhalation aginst closed airways- all this maximises intake of psychoactive substances, but increases tar and carbon monoxide content and increases pressure changes in the lungs.
An understanding of the full health risk in smoking marjuana is difficult to assess since the lack of disclosure by patients of their smoking habits - for fear of legal issues - does not permit clinicians to fully assess the results of smoking this drug.

Tuesday, 8 February 2011

The Effects of Indoor Mould on Asthma - Time to Act!

A comprehensive new review on childhood asthma thoroughly assesses the current understanding of the effect of multiple potential indoor causes of childhood asthma.

As preventative measures the following three actions were investigated:
  1. Avoiding or reducing the source of an indoor factor that might have adverse effects on the onset of asthma
  2. Reducing the concentration of, or diluting, the indoor air pollutants through increased ventilation
  3. Increasing air exchange rates or removal of dust.
Each preventative suggestion was weighed up for suitability of use against each potential cause of childhood asthma that has been researched so far. Factors influencing the assessment included practicality and affordability alongside the likelihood that it would help prevent asthma in children.

As a summary of the findings of this review for this blog, specific causes are listed below with conclusions inset underneath:
  • Tobacco smoke
    • Strong need to avoid exposing children - no more research needed
  • Cleaning activities
    • No evidence that this is bad for children - more research needed
  • Emissions of gas cooking
    • Ensure extensive ventilation is in place - precautionary advice
  • Renovation & redecoration activities
    • Ensure extensive ventilation is in place - precautionary advice
  • Traffic related pollutants which penetrate indoors
    • Probably not a strong influence on childhood asthma, but avoid if possible
  •  Pets and pet derived allergens
    • Avoidance not recommended - no more research needed
  • Mite allergens
    • Avoidance not possible, ventilate to avoid damp
  • Dampness and mould derived components
    • Strong need to avoid exposing children - treat sources of damp and ventilate well
Overall the actions recommended are:
we conclude that it is time to act against exposure to environmental tobacco smoke, water damage and insufficient ventilation in order to prevent asthma onset in childhood. As a precautionary principle, more attention has to be paid for a general increased air exchange rate and active ventilation. More research is needed for a better understanding of potential adverse health effects on the frequent use of cleaning chemical agents, on emissions from paintings, on floorings and other building materials and finally on damp related mould components.
It it noteworthy that the most cost effective and widely applicable action we can all take to avoid the onset of childhood asthma is to ensure that our homes are well ventilated with a good airflow encouraged. Of course this isn't easy in cold weather but is nonetheless important. Suggestions include extractor fans are good at keeping moisture levels down in the rooms they are fitted and allow little cold air into the room, keep lids on pans of boiling water to avoid introducing huge amounts of steam into the house and so on.

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