Adrenal insufficiency
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Cortisol and aldosterone are important hormones our bodies need in order to stay healthy, fit and active. They are produced by the adrenal glands which are sited at the top of each of our kidneys. Sometimes our adrenal glands may not be able to produce enough cortisol and aldosterone, for example when the glands are mistakenly attacked and destroyed by a person’s immune system – this is Addison’s disease (see also addisonsdisease.org.uk). The lost hormones can be replaced by medication from an endocrinologist and the patient can live a normal life. This form of adrenal insufficiency is not a feature of aspergillosis.
Unfortunately, people who take corticosteroid medication (e.g. prednisolone) for longer periods of time (more than 2-3 weeks) can also find that they have low levels of cortisol as their corticosteroid medication can suppress the production of their own cortisol, especially if high doses are taken.
Once the corticosteroid medication is stopped your adrenal glands will usually re-activate but it may take some time which is why your doctor will tell you to slowly taper down your dose of corticosteroid carefully over several weeks, to allow your adrenal glands to recover.
What has this got to do with aspergillosis?
People with chronic forms of aspergillosis & asthma can find themselves taking corticosteroid medication for quite long periods of time in order to control their breathlessness and allow comfortable breathing. Consequently, they may find that they have to take care when reducing their dose of corticosteroid and proceed gradually to allow their own natural cortisol production to resume safely. Reducing too quickly can cause a range of symptoms including fatigue, fainting, nausea, fever, dizziness.
These are powerful drugs and must be handled with care so if you have any concerns contact your GP without delay.
Other medication you may be taking to treat aspergillosis has also rarely been associated with causing adrenal insufficiency e.g. some azole antifungal medication, so it is worthwhile to remain vigilant for relevant symptoms (see list above). However, note that symptoms such as fatigue are very common in someone with aspergillosis.
For other details on taking corticosteroid medication see the steroids page
Steroid Emergency Card
The NHS has issued a recommendation that all patients who are steroid dependant (i.e. should not abruptly stop corticosteroid medication) carry a Steroid Emergency Card to inform health practitioners that you need daily steroid medication in the event you are taken into hospital and are unable to communicate.
Information on obtaining a card can be found here.
NOTE patients attending the National Aspergillosis Centre in Manchester can collect a card at pharmacy
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Facemask Anxiety
[et_pb_section fb_built="1" admin_label="section" _builder_version="4.16" global_colors_info="{}" theme_builder_area="post_content" custom_padding="4px||4px||true|false"][et_pb_row admin_label="row" _builder_version="4.16" background_size="initial" background_position="top_left" background_repeat="repeat" global_colors_info="{}" theme_builder_area="post_content"][et_pb_column type="4_4" _builder_version="4.16" custom_padding="|||" global_colors_info="{}" custom_padding__hover="|||" theme_builder_area="post_content"][et_pb_text admin_label="Text" _builder_version="4.16" background_size="initial" background_position="top_left" background_repeat="repeat" global_colors_info="{}" theme_builder_area="post_content"]Facemask wearing is still an important part of how we protect ourselves and others from COVID-19 infection and will continue to be so for some time yet. Wearing facemasks in public is something government regulations currently require us to do. For most people that doesn't cause a problem, but for some groups, it is a difficult thing to comply with.
For some, there are medical reasons for their inability to wear a facemask and for that reason, they are granted exemptions from government guidance (Exemptions in England, Exemptions in Wales, Exemptions in Scotland, Exemptions in NI).
The mental health charity MIND has considered the difficulties faced by people who are prone to suffering from anxiety that is difficult to control and in particular the anxieties associated with facemasks. This may be anxiety when attempting to wear a facemask, but it can also include anxiety caused when not wearing a facemask in situations where many other people will be wearing one. MIND has written a useful information page that addresses all of these difficulties and offers tips on how to manage those emotions - even those who are wearing a facemask and who feel anxious about being around others not wearing one.
We can all suffer from anxiety when placed in unfamiliar, unusual or uncomfortable situations - none more so than in a global pandemic - so there is something to learn for most of us in this article
Click here to go to the MIND website page on facemask anxiety.
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Differences between ABPA and CPA
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Allergic broncho pulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA) are two different types of aspergillosis. They are both chronic diseases but they differ in mechanisms and often presentation. Do you know the differences between the two?
This article will compare the biology, the symptoms and the diagnosis/treatment of the two diseases.
The Biology
An overview:
The ultimate cause of both ABPA and CPA is failed clearance of Aspergillus spores (conidia) from the lungs which leads to disease. However, the exact mechanism of how disease is caused in the two is quite different. The main difference is that ABPA is an allergic reaction to Aspergillus spores whereas CPA is an infection.
Let’s first look at ABPA. As previously said, ABPA is caused by an allergic reaction to Aspergillus spores. The reaction is exaggerated by co-morbid diseases like cystic fibrosis (CF) and asthma. As is described on the ABPA page, Aspergillus spores in and of themselves do not cause allergic reactions - hence they are unknowingly breathed in by everyone every day. In healthy people, the spores are quickly removed out of the lungs and body. A reaction occurs when the spores are not cleared out of the lungs, giving them time to grow and produce hyphae (long thread-like structures) that release harmful toxins. The body then produces an allergic immune response to the germinating spores and the hyphae. This allergic response involves inflammation. Inflammation is the result of lots of different immune cells rushing to the area at once to try and fight off the invaders. Whilst it is needed in an effective immune response, it also causes swelling and irritation of the airways, producing some of the main symptoms associated with ABPA such as coughing and shortness of breath.
Now let’s look at CPA. CPA, as mentioned above, is not characterised by an allergic reaction to Aspergillus spores. This disease is less clear cut than ABPA and is much less common. It is, however, caused by spores not being cleared effectively from the lungs. In this case, they set up residence in damaged lungs or cavities present within the lungs and begin to germinate there. Areas of damaged lung are much easier for infections to invade as there are fewer immune cells to fight them off (note that patients with CPA usually have a functioning immune system – ie. they are not immunocompromised). These cavities are usually the result of previous lung infections such as chronic obstructive pulmonary disorder (COPD) or tuberculosis (TB).
Some CPA patients have multiple underlying conditions. In a 2011 study, details of underlying conditions of 126 CPA patients in the UK were identified; it was found that tuberculosis, non-tuberculous mycobacterial infection and ABPA (yes, ABPA can be a risk factor for CPA) were the predominant risk factors for development of CPA (read the full study here - https://bit.ly/3lGjnyK). The Aspergillus infection can grow in damaged areas deep within the lungs and occasionally begin to invade the surrounding tissue. When this happens, immune cells in the surroundings areas usually fight off the infection and so it is prohibited from completely invading the lung tissue. This periodic spreading of the Aspergillus infection can, however, damage nearby blood vessels causing one of the main symptoms associated with CPA which is coughing up blood (haemoptysis).
Which immune cells are detected?
ABPA:
- As ABPA is predominantly an allergic infection, IgE antibody levels rise dramatically (>1000) as part of the body’s allergic immune response. IgE plays an important role in allergy as it stimulates other immune cells to release chemical mediators. These chemicals help to get the allergen out of your body and/or recruit other immune cells to help out as well. One of these well-known chemicals is histamine. Total IgE levels and Aspergillus-specific IgE levels are both raised in patients with ABPA.
- IgG antibodies to Aspergillus are also often elevated; IgG is the most common type of antibody and works by binding to the Aspergillus antigens which leads to their destruction.
- Eosinophils can be raised which work by releasing toxic chemicals that destroy the invading pathogen.
CPA:
- Raised levels of Aspergillus IgG antibodies are present
- IgE levels may be slightly elevated in CPA patients, but not as high as ABPA patients
Symptoms
Whilst there are overlaps in symptoms between the two diseases, some symptoms are more common with one type of aspergillosis.
ABPA is associated with allergic symptoms such as coughing and production of mucus. If you have asthma, ABPA will most likely result in worsening of your asthmatic symptoms (such as wheezing and shortness of breath). Fatigue, a fever and general feeling of weakness/illness (malaise) can also be present.
CPA is less associated with production of mucus and more with coughing and coughing up blood (haemoptysis). Symptoms such as fatigue, breathlessness and weight loss are also seen.
In a Facebook poll put out by the National Aspergillosis Centre, this question was posed separately to people with ABPA and CPA:
‘What aspect(s) of your current quality of life are you most concerned about and would like to improve the most?’
The top 5 answers for ABPA were:
- Fatigue
- Breathlessness
- Coughing
- Poor fitness
- Wheeze
The top 5 answers for CPA were:
- Fatigue
- Breathlessness
- Poor fitness
- Anxiety
- Weight loss/coughing/coughing up blood/side effects of anti-fungals (note these answers all got the same number of votes)
This is helpful in directly comparing symptoms reported from patients themselves.
Diagnosis/treatment
The ABPA page on this website describes the updated diagnostic criteria – see this link https://aspergillosis.org/abpa-allergic-broncho-pulmonary-aspergillosis/
Diagnosis for CPA depends on radiological and microscopic findings, patient history and laboratory tests. CPA can develop into different forms such as chronic cavitary pulmonary aspergillosis (CCPA) or chronic fibrosing pulmonary aspergillosis (CFPA) – diagnosis is slightly different for each depending on radiological findings. The most common feature found on a CT scan of a CPA patient is an aspergilloma (morphological appearance of a fungal ball). Whilst this is very characteristic of CPA it cannot alone be used to determine a diagnosis and requires a positive aspergillus IgG or precipitins test for confirmation. Lung cavities present for at least 3 months may be seen with or without an aspergilloma, that, along with serological or microbiological evidence, can indicate CPA. Other tests such as Aspergillus antigen or DNA, biopsy showing fungal hyphae on microscopy, Aspergillus PCR, and respiratory samples that grow Aspergillus in culture are also indicative. Together with symptoms described by the patient, a combination of these findings is required to make a sure diagnosis.
Treatment for both diseases usually involves triazole therapy. For ABPA, corticosteroids are often used to control the body’s response to the spores and itraconazole is the current first-line antifungal treatment. Biologics may be an option for those with severe asthma. See more about biologics here - https://aspergillosis.org/biologics-and-eosinophilic-asthma/.
For CPA, the first-line treatment is itraconazole or voriconazole and surgery may be suitable to remove an aspergilloma. Diagnosis and a treatment plan is made by a respiratory consultant.
Hopefully this has given you a clearer picture on the two diseases. The main takeaway is that ABPA is characterised by an allergic reaction to aspergillus spores whereas CPA is not.
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The importance of microbiomes
[et_pb_section fb_built="1" admin_label="section" _builder_version="4.16" global_colors_info="{}" theme_builder_area="post_content"][et_pb_row admin_label="row" _builder_version="4.16" background_size="initial" background_position="top_left" background_repeat="repeat" global_colors_info="{}" theme_builder_area="post_content" custom_margin="11px|auto|11px|auto|true|false"][et_pb_column type="4_4" _builder_version="4.16" custom_padding="|||" global_colors_info="{}" custom_padding__hover="|||" theme_builder_area="post_content"][et_pb_text admin_label="Text" _builder_version="4.16" background_size="initial" background_position="top_left" background_repeat="repeat" global_colors_info="{}" theme_builder_area="post_content"]Microbiomes are all the microorganisms (bacteria, fungi, viruses etc.) that are present in a particular area in the body. These are found in places such as the gut, lungs and mouth and microbiomes in different areas are made up of a different distribution of species. They are beneficial to our bodies and influence a wide range of things such as our immune system, mental health and respiratory health. In the average healthy person, these different species exist in a regulated balance to perform various functions and confer health benefits - they provide nutrients that we cannot make ourselves. An imbalance (called dysbiosis) between the species of microorganisms present is heavily associated with disease.
See more about microbiomes on this page - https://aspergillosis.org/the-host-its-microbiome-and-their-aspergillosis/?highlight=microbiomes
The gut microbiome – mental health & the immune system
The most well-studied microbiome is that of the gut. In the gut there are about 100 trillion (100 000 000 000 000!) bacteria of around 1000 different species. These bacteria can communicate with the brain via something called the microbiota-gut-brain axis, which describes a two-way interaction between the brain and the gut. The gut is able to send messages to the brain in the form of chemicals (called neurotransmitters) which travel along nerves and through the bloodstream to reach the brain where they have various effects. These neurotransmitters are produced by bacteria that live within the gut.
The gut microbiome is a regulator of stress and anxiety levels and has a strong influence on mood and depression. This has been demonstrated through several studies. For example, mice studies have shown that those who don’t have a gut microbiome (called germ-free mice) have an abnormally strong stress response in comparison to mice that have a gut microbiome[1]. Interestingly, this heightened response was reduced after the addition of a resident gut bacteria called Bifidobacterium. This species, along with another key species called Lactobacillus, has been shown to significantly reduce anxiety in humans[2]. Faecal microbiota transplantation (FMT) is a process where faeces from a healthy donor are transplanted into a recipient to restore the balance of bacteria in their gut. FMT experiments were performed from healthy patients to those with depressive and anxiety-like symptoms and vice versa; in every case, ill patients reported a reduction in symptoms after receiving the transplantation and healthy patients reported an increase in symptoms[3]. Finally, serotonin is a hormone that acts in the brain to cause positive and happy moods. This hormone is produced by gut bacteria and, in fact, about 90% of the body’s serotonin is made by these bacteria[4]. These are just a few examples that demonstrate the impacts that gut bacteria have on mental health.
To read more about the impact of the gut microbiome on mental health, check out this article by the BBC - https://bbc.in/3npHwet
Our immune system (i.e. the system that helps us fight off infection) is also affected by the gut microbiome. Various gut bacteria are able to stimulate immune cells (T cells) to specialise into a specific type of cell called T regulatory cells (or Tregs). Tregs suppress the immune system and hence exaggerated allergic reactions (e.g. eczema) can develop from decreased activation of these immune cells. In the gut, some bacteria are capable of activating Tregs. This suggests the possibility of administering these species to patients with over-active allergic responses to help ease allergy and inflammation. This hypothesis is yielding initial results that are encouraging, for example in eczema, https://nationaleczema.org/topical-microbiome/. Also see the section at the end on probiotics.
Lung & gut microbiomes – allergy and asthma
The lower airways are home to a different population of microorganisms – called the lung microbiome. The makeup of this microbiome is different to that of the gut. There are far less bacteria present in the lungs compared to the gut and this environment is much harder to study, mainly because methods of obtaining lung samples are invasive. It was initially believed that the lungs were a sterile environment containing no bacteria and the lung microbiome was not discovered until recent years, therefore, much less is known about this population compared to the gut.
What is known is that the lung microbiome does play a role in respiratory health and a reduced diversity of microbe species is associated with disease – with more reduction in diversity being associated with more severe disease. Importantly, the lung microbiome is connected to the gut microbiome through the lung-gut axis and respiratory and gastrointestinal diseases are often present together. The two are linked through the immune system and communication occurs, as with the gut and the brain, through chemical messengers. This means that changes in the gut microbiome seem to have an effect on airway allergic responses and asthma as well. Several studies have shown that asthmatic patients have an altered range of species in their lung and gut microbiomes compared to a non-asthmatic person, and this imbalance is thought to contribute to the hypersensitivity and hyperreactivity of the immune system.
One bacterial species called Bacteroides fragilis (B. fragilis) has been shown in experimental mouse models (intended to simulate asthma) to regulate the balance between the type of immune response that the body produces[5]. Allergic inflammatory responses are produced by a specific pathway (called the Th2 pathway) whilst non-allergic immune responses are produced by a different pathway (Th1). This species of bacteria is important because it controls the balance between these two pathways to ensure that neither of the responses become dominant. B. fragilis relies on a carbohydrate called N-glycan and N-glycan production is reduced in patients with severe asthma[6]. This makes it harder for B.fragilis to grow so it is more likely that an allergic (Th2) response could dominate as the balance between the two pathways becomes less regulated. This is one example of how important gut bacteria can be in a disease like allergic asthma.
Click this link to read more about the gut-lung connection and its relevance in COVID-19 - https://bit.ly/3FooPOp
The future – probiotics, FMT and research
Probiotics are defined as ‘live microorganisms which when administered in adequate amounts confer a health benefit on the host (person)’. They come in different forms and are taken for various health benefits, with different ones having different compositions of bacteria.
Probiotics have been studied in recent years for use in asthmatic patients with allergic sensitisation. Some experiments have been done to test probiotics as a treatment for asthma and have proved to be successful. For example, one study gave probiotics to 160 asthmatic children aged 6-18 as capsules for 3 months; the results showed that the patients had lowered asthmatic severity, improved asthma control, increased peak expiratory flow rate and decreased IgE (a marker of allergy) levels[7]. Notably, lots of the studies done on this topic have been in mice or children and the results are inconsistent, so more research is needed in this area before probiotics can be recommended as a treatment.
FMT is an established effective treatment for Clostridium difficile infections, but experiments have not yet been fully studied in allergic diseases. There is currently an ongoing clinical trial for oral encapsulated FMT in the treatment of peanut allergy and phase I was completed but results have not yet been published. As these trials become more numerous, it is likely that they will extend to allergic asthma and possibly even allergic Aspergillus-sensitisation. As it stands, there is some resistance to such trials as some people are opposed to, or ‘grossed out’ by, the idea of transferring stool from one person to another. However, in reality, FMT is not a transplant of faeces, but of microbiota from the intestines. Furthermore, not all FMT trials have had positive outcomes – a trial in haematopoietic stem cell transplant patients proved to be fatal for one man who received a donor sample that hadn’t been screened for a drug-resistant type of E.coli [8]. FMT research for allergy is still in early stages and more research is needed to ensure its safety, but there is no doubting it has great potential for the future.
Nevertheless, maintaining a healthy balance of bacteria in your gut and lung microbiomes is important for everyone’s health and wellbeing. This is helped by having a healthy balanced diet containing lots of fibre and eating foods that contain lots of beneficial bacteria like natural yoghurt or kefir. Although they are not formerly recommended as treatment by the NHS, you may want to consider taking a probiotic. However, you should be aware that probiotics are considered dietary supplements as opposed to medication and so the manufacturing of these products is not regulated, meaning you cannot be certain that they contain the bacteria stated on the label. It is also worth noting that probiotics used in clinical trials are likely to be more effective than ones that can be bought over the counter as they probably contain a higher dose and more species.
There is good evidence that taking a probiotic whilst on antibiotics is effective at reducing antibiotic-associated diarrhoea, but again, this is not yet a recommended treatment. The main species to look out for are Lactobacillus (L) rhamnosus. L. acidophilus and L. casei. Also, Bifidobacterium (B) lactis and Saccharomyces (S) boulardii. In order for these probiotics to be effective, a dose of 10 billion (10^10) cfu (bacteria) is needed. If the product does not state the dosage, it is likely that it doesn't contain enough bacteria to have any significant effect. Furthermore, a dose way over 10 billion is not beneficial and may cause adverse health effects such as abdominal pain. A study done in The Netherlands compiled a list of recommended probiotics from various manufacturers for the treatment of diarrhoea whilst taking antibiotics. This study was not done in the UK so not all of these probiotics may be available here but it is worth seeing. See this list here. Note that a three-star rating is the best, but a one-star rating is still worth recommendation.
To conclude, we know that microbiomes are extremely important for our health, so look after yours as much as you can.
Want to know what to eat for a healthy gut? Follow this link - https://bbc.in/31Rhfx1
[1] https://physoc.onlinelibrary.wiley.com/doi/10.1113/jphysiol.2004.063388
[2] https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/assessment-of-psychotropiclike-properties-of-a-probiotic-formulation-lactobacillus-helveticus-r0052-and-bifidobacterium-longum-r0175-in-rats-and-human-subjects/2BD9977C6DB7EA40FC9FFA1933C024EA
[3] https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-020-02654-5
[4] https://ieeexplore.ieee.org/document/8110878
[5] https://academic.oup.com/glycob/article/25/4/368/1988548
[6] https://www.researchgate.net/publication/233880834_Transcriptome_analysis_reveals_upregulation_of_bitter_taste_receptors_in_severe_asthmatics
[7] Efficacy of Lactobacillus Administration in School-Age Children with Asthma: A Randomized, Placebo-Controlled Trial - PubMed (nih.gov)
[8] https://www.nejm.org/doi/full/10.1056/NEJMoa1910437?query=featured_home[/et_pb_text][/et_pb_column][/et_pb_row][/et_pb_section]
Grieving for the life you once had
[et_pb_section fb_built="1" admin_label="section" _builder_version="4.16" global_colors_info="{}" theme_builder_area="post_content" custom_padding="11px||11px||true|false"][et_pb_row admin_label="row" _builder_version="4.16" background_size="initial" background_position="top_left" background_repeat="repeat" global_colors_info="{}" theme_builder_area="post_content"][et_pb_column type="4_4" _builder_version="4.16" custom_padding="|||" global_colors_info="{}" custom_padding__hover="|||" theme_builder_area="post_content"][et_pb_text admin_label="Text" _builder_version="4.16" background_size="initial" background_position="top_left" background_repeat="repeat" global_colors_info="{}" theme_builder_area="post_content"]This article was published by the Cystic Fibrosis Foundation and is a personal account of a young woman with CF and trying to come to terms with the limitations that loss of lung function has placed on her young life. There is a grief for her lost life, the one where she was fitter and stronger and could do so much more,
Grieving the life I once had
Just like any grief, it has a process that we all go through, and has a new life at the other end. The article is well worth a read.
NB Aspergillosis Support Groups run by the National Aspergillosis Centre in the UK can be found on Facebook.
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Vaccine Types
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Vaccines. Something most, if not all of us, are familiar with. MMR (Measles, Mumps & Rubella), TB (Tuberculosis), Smallpox, Chicken Pox, and the more recent HPV (Human Papillomavirus) and Covid-19 vaccines are just a few of the many available to protect us from harmful pathogens (an organism that causes disease like bacteria or viruses – aka 'germs'). But what exactly is a vaccine, and how does it protect us?
Firstly, to understand vaccines, it helps to have a fundamental understanding of the immune system. The immune system is the body's natural defence against harmful pathogens. It is a complex system of organs and cells that work together to help fight off infection caused by invading pathogens. When a 'germ' enters our body, the immune system triggers a series of responses to identify and destroy it.
Outward signs we are having an immune response are:
- A raised temperature (fever) and uncontrollable shivering (Rigors).
- Inflammation; this can be internal or visible on the skin's surface – for example, from a cut.
- Coughing & Sneezing (mucus traps germs, which are then removed by the action of coughing or sneezing).
Types of immunity:
Innate (also called nonspecific or natural) immunity: We are born with a combination of physical (skin and mucous membranes in the respiratory and gastrointestinal tracts), chemical (for example, stomach acid, mucous, saliva and tears contain enzymes that breakdown the cell wall of many bacteria1), and cellular (natural killer cells, macrophages, eosinophils are just a few2) defences against pathogens. Innate immunity is a type of general protection designed to immediately respond to the presence of a pathogen.
Adaptive immunity: The adaptive, or acquired, immune response is more specific to an invading pathogen and occurs after exposure to an antigen (a toxin or foreign substance which induces an immune response) either from a pathogen or vaccination.3
Below is an excellent video from TedEd that provides a simple yet detailed explanation of how the immune system works.
Types of vaccines
There are several different types of vaccines that use various mechanisms to 'teach' our immune systems how to fight off specific pathogens. These are:
Inactivated vaccines
Inactivated vaccines use a version of the pathogen that has been killed. These vaccines generally require several doses or boosters for immunity to be ongoing. Examples include Flu, Hepatitis A and Polio.
Live-attenuated vaccines
A live-attenuated vaccine uses a weakened live version of the pathogen, mimicking natural infection without causing serious disease. Examples include Measles, Mumps, Rubella, and Chickenpox.
Messenger RNA (mRNA) vaccines
An mRNA vaccine contains no actual part of the pathogen (alive or dead). This new type of vaccine works by teaching our cells how to make a protein that will in turn, trigger an immune response. In the context of Covid-19 (the only mRNA vaccine approved for use in the form of the Pfizer and Moderna vaccinations), the vaccine instructs our cells in making a protein found on the surface of the Covid-19 virus (the spike protein). This causes our bodies to create antibodies. After delivering the instructions, the mRNA is immediately broken down.4
Subunit, recombinant, polysaccharide, and conjugate vaccines
Subunit, recombinant, polysaccharide, and conjugate vaccines do not contain any whole bacteria or viruses. These vaccines use a piece from the pathogen's surface —like its protein, to elicit a focused immune response. Examples include Hib (Haemophilus influenzae type b), Hepatitis B, HPV (Human papillomavirus), Whooping cough (part of the DTaP combined vaccine), Pneumococcal and Meningococcal disease.5
Toxoid vaccines
Toxoid vaccines are used to protect against pathogens that cause the release of toxins. In these cases, it is the toxins that we need to be protected from. Toxoid vaccines use an inactivated (dead) version of the toxin produced by the pathogen to trigger an immune response. Examples include Tetanus and Diphtheria.6
Viral Vector
A viral vector vaccine uses a modified version of a different virus (the vector) to deliver information in the form of a genetic code from a pathogen to our cells. In the case of the AstraZeneca and Janssen/Johnson & Johnson vaccines and Covid-19, for example, this code teaches the body to make copies of the spike proteins – so if exposure to the actual virus occurs, the body will recognise it and know how to fight it off.7
The video below was developed by Typhoidland and The Vaccine Knowledge Project and describes what happens inside our cells when we are infected with a virus - using Covid-19 as the example.
References
- Science Learning Hub. (2010). The body's first line of defence. Available: https://www.sciencelearn.org.nz/resources/177-the-body-s-first-line-of-defence Last accessed 18 Nov 2021.
- Khan Academy. (Unknown). Innate Immunity. Available: https://www.khanacademy.org/test-prep/mcat/organ-systems/the-immune-system/a/innate-immunity Last accessed 18 Nov 2021.
- Molnar, C., & Gair, J. (2015). Concepts of Biology – 1st Canadian Edition. BCcampus. Retrieved from https://opentextbc.ca/biology/
- Mayo Clinic Staff. (Nov 2021). Different types of COVID-19 vaccines: How they work. Available: https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/different-types-of-covid-19-vaccines/art-20506465 Last accessed 19 Nov 2021.
- Office of Infectious Disease and HIV/AIDS Policy (OIDP). (2021). Vaccine Types. Available: https://www.hhs.gov/immunization/basics/types/index.html Last accessed 16 Nov 2021.
- Vaccine Knowledge Project. (2021). Types of vaccine. Available: https://vk.ovg.ox.ac.uk/vk/types-of-vaccine Last accessed 17 Nov 2021.
- CDC. (Oct 2021). Understanding Viral Vector COVID-19 Vaccines. Available: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/viralvector.html#:~:text=First%2C%20COVID%2D19%20viral%20vector,is%20called%20a%20spike%20protein Last accessed 19 Nov 2021.
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Aspergillosis and the benefits of gentle exercise – a patient’s perspective
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Cecilia Williams suffers from aspergillosis in the form of an aspergilloma and Chronic Pulmonary Aspergillosis (CPA). In this post, Cecilia talks about how a light but regular exercise regime has helped improve her health and wellbeing.
I downloaded the exercise guide (available here) in September this year. My oxygen levels had been dreadful, and I wanted to do some form of at-home pulmonary rehabilitation. I was surprised that the exercises in the programme were to be undertaken daily, as previous pulmonary programmes at the hospital were only three times a week. However, this programme was a lot simpler.
I do a stretching routine for a few minutes before the exercises, and I have now introduced 2.5kg weights, but I would do them without weights when I first started. I started at the lowest number of reps for the seated and standing exercises and have gradually increased to the recommended sets. I take my time to do the exercises as I can get breathless, and the time it takes depends on the kind of day I’m having. I break the 30-minute step into two; one first thing in the morning and one after lunch. If I go for a walk outside, I just do the other exercises and no step routine. I make a conscious effort to concentrate on my breathing as indicated on the chart. I use the breathing techniques recommended by Phil (National Aspergillosis Centre Specialist Physiotherapist, video available here), which has been my go-to for getting my breathing back to normal.
When I started this programme, my oxygen saturation levels were poor. I was breathless for long periods, and I would suffer all day with terrible nasal congestion and postnasal drip - I was forever steaming with menthol crystals. Incorporating the exercises and breathing techniques into my daily routine (first thing in the morning in my bedroom with the windows open) has had a profound effect. My congestion clears easier without steaming. I can take deeper breaths and hold my breath for longer. I have noticed the time it takes for me to recover from episodes of low oxygen levels and breathlessness has also improved. I do all the exercises on the table; the balance ones are essential, and with time and practice, I am improving - though I haven’t started doing them with my eyes closed – I am not there yet! I hope that writing my account of the benefits even the lightest of exercise programmes has gives others confidence and encouragement to undertake an at-home exercise programme.
If you want to know more about exercising with aspergillosis, our Specialist Physiotherapist Phil Langdon has a talk available via our YouTube channel here.
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Vitamin D supplements
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Between about late March and September each year in the UK most of us are able to generate enough vitamin D from sunlight exposure, but from the months of October to March our bodies do not get enough vitamin D from sunlight. A lack of vitamin D affects teeth, muscles and can lead to bone deformities. Whilst there isn't specific evidence that vitamin D affects aspergillosis, deficiency has been linked with other chronic illnesses.
Vitamin D can be found in foods such as oily fish, red meat and egg yolks but the NHS recommends that everyone takes vitamin D supplements between October to March to ensure we have sufficiently high levels. The recommended dose for adults and children over 1 is 10 micrograms (or 400 IU) per day.
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Walk and paint yourself back to health & wellbeing
One of the subjects discussed at our online weekly patient & carer support meeting for the National Aspergillosis Centre in Manchester, UK this week was the importance of maintaining our health & wellness so that we may maintain our best possible quality of life regardless of having a chronic infection.
Exercise is difficult when you have little energy, and one or two participants compared this to being given just a few teaspoons of energy that have to be eeked out carefully over the course of the day to ensure that everything that needed to be done was done. One person commented that some days they only wake up with one teaspoon of energy!
A little gentle exercise every day could play a major role in maintaining your health & wellness and can help with energy too if you keep it up. Over time it will help you breathe and prevent muscle loss.
We can all get great advice from our GP's or Physiotherapists on specific exercises we can do in the home, but one patient mentioned that she had successfully worked their way back to fitness and enjoyment using the walking groups provided by the UK charity 'Walking for Health' who have a network of walking groups led by responsible trainers throughout the UK, specifically for people with asthma.
Well worth a try!
Another aspect of health & wellbeing is emotional health. It can be easy to become isolated and there is only so much entertainment to be found on TV. Another member of the support meeting suggested one of the many Zoom groups that have been set up to teach art!
There are many options online and many different media you can work with.
For example:
https://adult.art-k.co.uk/adult-zoom-classes/
https://www.artcoursework.com/class-courses/free-beginners-learn-to-draw-and-paint-course/
https://www.eventbrite.co.uk/d/online/free--arts--classes/?page=1
Good luck! Doing something is always better than doing nothing.
Antifungal Drug Pipeline
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Many of our patients already know of the increasing need for new antifungal drugs; treatments for fungal diseases like aspergillosis have significant limitations. Toxicities, drug-drug interactions, resistance, and dosing are all issues that can complicate therapy; therefore, the more treatment options we have, the more likely we are to find an optimal therapeutic option for patients.
Developing antifungal drugs is difficult because of the biological similarities between people and fungi; we share many of the same biological pathways as fungi, creating issues in developing safe antifungals. To develop new antifungal drugs, researchers must look at how they can exploit some of the differences we do have.
Below is a layman’s breakdown of a recently published review that looked at seven antifungal drugs currently in various stages of development. The majority of new antifungals have been new versions of old drugs, but the ones discussed in this review have new mechanisms of action and different dosing regimens, so, if approved, these drugs could provide a ray of hope in the not so distant future in terms of treatment.
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Rezafungin
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Rezafungin is currently in phase 3 of development. It is a member of the echinocandin class of drugs, including micafungin and caspofungin; Echinocandins work by inhibiting a fungal cell wall component essential to homeostasis.
Rezafungin has been developed to retain the safety benefits of its echinocandin predecessors; while enhancing its pharmacokinetic and pharmacodynamic properties to create a unique, longer-acting, more stable treatment that allows for weekly intravenous rather than daily administration, potentially expanding treatment options in the setting of echinocandin resistance.
Fosmanogepix
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Fosmanogepix is known as a first-in-class drug (so first of its kind antifungal) that blocks the production of an essential compound that is important for the construction of the cell wall and self-regulation. Blocking the production of this compound weakens the cell’s wall enough that the cell can no longer infect other cells or evade the immune system. It is currently in Phase 2 clinical trials and is showing promising results in the oral and intravenous treatment of multiple invasive fungal infections, demonstrating efficacy in multi-drug resistant and other difficult-to-treat infections.
Olorifim
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Olorifim falls under an entirely new class of antifungal drugs called orotomides. The orotomides have a distinct mechanism of action, selectively targeting a key enzyme in pyrimidine biosynthesis. Pyrimidine is an essential molecule in DNA, RNA, cell wall and phospholipid synthesis, cell regulation, and protein production, so when Olorofim targets this enzyme, it profoundly affects the fungi. Unfortunately, Olorifim isn’t broad spectrum, and it only kills a few fungi – pertinently, Aspergillus, and the fungus that causes valley fever (which affects the brain), Coccidioides. Since its discovery, it has progressed through pre-clinical studies and phase 1 human trials and is currently an ongoing phase 2 clinical trial testing its use orally and intravenously.
Ibrexafungerp
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Ibrexafungerp is the first of a new class of antifungals called Triterpenoids. Ibrexafungerp targets the same essential component of the fungal cell wall that the echinocandins do, but it has an entirely different structure, making it stabler and meaning it can be given orally; differentiating Ibrexafungerp from the three currently available echinocandins (caspofungin, micafungin, andulafungin), which can only be given intravenously limiting their use to hospitalised patients and those with indwelling venous access.
There are two ongoing phase 3 trials of ibrexafungerp. The most extensive enrolling study to date is the FURI study, which evaluates the efficacy and safety of Ibrexafungerp among patients with severe fungal infection and who are unresponsive or intolerant of standard antifungal agents. The oral formulation was recently approved by the USA’s Food and Drug Administration (FDA) for the treatment of vulvovaginal candidiasis (VVC).
Oteseconazole
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Oteseconazole is the first of several tetrazole agents designed with the goal of greater selectivity, fewer side effects, and improved efficacy compared to currently available azoles. Oteseconazole has been designed to tightly bind to an enzyme called cytochrome P450. When we discussed earlier fungi and humans being similar, cytochrome P450 is one of those similarities. Human cells contain various species of cytochrome P450, which are responsible for many important metabolic functions. Therefore, if azole antifungal agents inhibit the human cytochrome P450, the result can be adverse reactions. But, unlike other azole antifungals, Oteseconazole only inhibits the fungal cytochrome p450- not the human one because of its affinity for the target enzyme (cytochrome P450) is greater. This should mean fewer drug-drug interactions and less direct toxicity.
Oteseconazole is in phase 3 of development and is currently under FDA consideration for approval to treat recurrent vulvovaginal candidiasis.
Encochleated Amphotericin B
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Many of our patients will already be aware of Amphotericin B, which has been around since the 1950s. Amphotericin B falls under the class of drugs called Polyenes- the oldest class of antifungal drugs available. They kill fungi by binding to ergosterol which acts to maintain cell membrane integrity. The drug works by stripping away the ergosterol, causing holes in the cell membrane, making it leaky enough to fail. But, polyenes also interact with cholesterol in human cell membranes, meaning they have significant toxicities. Encochleated Amphotericin B has been developed to avoid these significant toxicities – its novel lipid nanocrystal design allows for drug delivery directly to the infected tissues, shielding the body from unnecessary exposure – and it can be given orally, potentially reducing hospital stays.
Encochleated Amphotericin B is currently in phases 1 & 2 of development, so a little way off. Still, it promises the potential of an oral drug with little, if any, of the typical toxicities of amphotericin B.
ATI-2307
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ATI-2307 is in the very early stages of development and is a new antifungal drug with a unique mechanism of action. ATI-2307 inhibits mitochondrial function (mitochondria are structures within cells that convert food to energy), decreasing the production of ATP (adenosine triphosphate), which is the molecule that carries energy, leading to growth inhibition.
As mentioned earlier, ATI-2307 is still in the early stages. Still, researchers have completed three Phase 1 clinical studies that demonstrated it was well tolerated in humans at anticipated therapeutic dose levels. Thus, the clinical role for ATI–2307 is unclear; however, its broad in vitro activity against a host of important fungal pathogens, including multi-drug resistant organisms, could translate into a critical role for this compound, especially for fungal infections due to drug-resistant organisms such as azole-resistant Aspergillus species.
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