Aspergillus – Pseudomonas interactions; a match made in heaven or hell?

In the last years clinicians and researchers have realised that the interactions between microorganisms in polymicrobial infections (when a single patient is colonised/infected with two or more pathogens) are relevant for the progression of the disease. Contacts between pathogens can affect their fitness (how well they can grow inside us) and also impact on the response of our immune system. However, the research into this novel and extremely complex area is still in its infancy and we need to gain much more information before being able to understand what is going on in each specific condition. It is suspected that in some interactions the microorganisms may compete with each other, which is usually good for us. However, in other types of interactions the pathogens may help each other, which is of course detrimental for the patients. In the case of Aspergillus – Pseudomonas interaction it is still not completely clear which is taking place, a positive or a negative interaction.

Pseudomonas (mainly the species Pseudomonas aeruginosa) is a common bacterial pathogen and Aspergillus (mainly the species Aspergillus fumigatus) is the most common fungal pathogen of the human respiratory tract. Both organisms are able to grow in the lungs of immunosuppressed individuals and also of patients with certain underlying diseases, such as bronchiectasis, chronic obstructive pulmonary disease (COPD), hospital acquired pneumonia and cystic fibrosis. Since the awareness of the importance of polymicrobial infections is quite recent, there are not many reports of the incidence of co-infection with these two pathogens yet. One of the few, from the end of 2018, reported a prevalence of co-infection in cystic fibrosis patients of 15.8% (1). That means that almost sixteen percent of all cystic fibrosis patients may be co-infected with both Pseudomonas and Aspergillus… This is of course not trivial!

 Several studies carried out in various laboratories around the world would suggest that the interaction between Aspergillus and Pseudomonas is of competitive nature. That would indicate that they weaken each other during co-infection, which could mean good news for patients. However, there are also results, including some clinical evidence, that suggest the opposite, the pathogens could be helping each other in the human lungs. What seems clear is that having both pathogens is not good for the patients (2). Therefore, we need to understand how these microbes interact during co-infection to be able to decide which course of action is best, should we treat against both or only one? Which one first, or both at the same time?

To address these questions my research group, in the Manchester Fungal Infection Group, is trying to understand the specific interactions that take place between Aspergillus fumigatus and Pseudomonas aeruginosa under conditions that are similar to co-infection of the human lung.

We want to discover which interactions are the important ones. This will help us understand what is going on during co-infection and we can then use this knowledge to improve the management and treatment of patients.

Dr Jorge Amich | MRC Career Development Fellow

Manchester Fungal Infection Group (MFIG)

1. Zhao J, Cheng W, He X, Liu Y.2018. The co-colonization prevalence of Pseudomonas aeruginosa and Aspergillus fumigatus in cystic fibrosis: A systematic review and meta-analysis. Microb Pathog 125:122-128.

2. Reece E, Segurado R, Jackson A, McClean S, Renwick J, Greally P.2017. Co-colonisation with Aspergillus fumigatus and Pseudomonas aeruginosa is associated with poorer health in cystic fibrosis patients: an Irish registry analysis. BMC Pulm Med 17:70.

Posaconazole works better than itraconazole and voriconazole against ABPA amongst Cystic Fibrosis patients

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.

Want to know more? Read the paper here!

Keep going! Keep going! Keep going!

At this month’s patient support meeting Phil Langridge, Specialist Physiotherapist at Manchester University NHS Foundation Trust, Wythenshawe Hospital, gave a fantastic talk all about spirometry and lung function tests.

He started the talk with a simple question “Do you look forward to lung function tests?” An audience member offered a simple reply “No, it’s purgatory”.

Lung function tests are hard. The thing is, they’re maximum function tests. The staff carrying out the tests sometimes sound a bit strict, firmly telling you to keep going and put more effort in. The tests are tough, and for some people they can take a while to recover from. That’s because they need maximum effort and it can take a lot out of some people.

Phil gave us an overview of most commonly used tests, starting with the spirometry test. Sometimes these tests can be done at your GP surgery with a practice nurse in a familiar setting. Sometimes they have to be done in hospital and this can lack privacy and be a bit intimidating. Try not to worry, staff understand this, just tell them you’re feeling nervous and they’ll do what they can to help so your test gives the best result possible.

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Yeast that live in the human gut can trigger the immune system to cause inflammation in the lung, especially in patients with ABPA.

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.

Read the paper here

Pulmonary Rehabilitation – is it worth it?

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.

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