A new study from the Netherlands has challenged the widely held opinion that airborne transmission of Aspergillus fumigatus between patients with cystic fibrosis (CF) does not occur.
Chronic Pulmonary Aspergillosis (CPA) is a chronic condition affecting patients with structural lung damage such as that caused by CF. It is generally accepted that patients become colonised by A. fumigatus following the inhalation of spores from the environment.
A recently published research paper suggests that Posaconazole works better than itraconazole and voriconazole against allergic bronchopulmonary aspergillosis (ABPA) in patients with Cystic Fibrosis.
ABPA patients tend to have a hypersensitive response to Aspergillus species which results in inflammation, airway destruction and bronchiectasis. Cystic fibrosis (CF) patients are at risk of ABPA which then speeds up lung function decline. The current ‘gold standard’ treatment is prednisolone to reduce inflammation. Azoles have been used effectively as steroid alternatives but have various side effects and tolerance issues.
In the newly published paper the authors wanted to know if posaconazole, which is known to be less toxic and better absorbed than other azoles, was more effective at treating ABPA.
They analysed data from 596 CF patients, and reviewed the specific Aspergillus IgE levels and azole levels in blood samples. 32 patients were identified and included in the analysis. 11 had itraconazole alone, 12 had two different azoles and 9 received all three azoles. In total, 30 received itraconazole, 13 received voriconazole, 18 received posaconazole.
The authors found IgE levels to be significantly reduced when posaconazole was used, but not the other azoles, suggesting that monitoring posaconazole levels and altering the dose given to the patient to attain greater serum levels of IgE gives improved blood test results in ABPA patients.
The yeast Candida albicans lives in the gut as a
commensal organism, usually without issue. C. albicans causes the body
to produce a particular kind of immune cell, called Th17 sensitive cells, that
stop the Candida from causing infections. A new research paper out this
month shows that the Th17 cells that react to Candida in the gut also
react to Aspergillus in the lung by a process called ‘cross reactivity’.
Cross reactivity was shown to increase the levels of Aspergillus
reactive Th17 cells in the blood of patients with Cystic Fibrosis, COPD and
asthma, especially during ABPA. This indicates that there is a direct link
between the normal, protective Th17 responses against Candida in the
gut, and harmful inflammation by Aspergillus in the lung.
In other words, problems in your lungs might be made worse by the normal immune response to Candida in your gut. This knowledge could affect the way we treat flare ups in future. For example, we already know that using antibiotics can increase the growth of Candida in the gut. This new information raises the possibility that increased Candida in the gut could cause increased lung inflammation or a ‘flare up’ of symptoms in patients with Aspergillosis, but further work would be needed to confirm this.
In last month’s patient meetings here at Wythenshawe Hospital, the topic of pulmonary rehabilitation (PR) came up. Some people said it had been useful, some people felt pushed into it, some people felt it was too much and actually made them feel worse instead of better.
This gave us food for thought and we went away to look at the literature. Has anyone studied the outcomes of PR from the patients’ perspective?
The answer was yes! In October last year a paper was published on exactly that, a survey of 1685 people with self-reported chronic lung disease in 29 countries.
As part of her PhD project, titled “Environmental drivers of azole-resistance in Aspergillus fumigatus and its relevance to human health”, Jennifer Shelton is conducting a UK-wide survey to determine background levels of Aspergillus fumigatus spores, and then testing them for resistance to azole fungicide drugs. To find out more about her project, have a read of her blog.