Who should be represented?

I said in my first post on the topic of replacing the PiA that I would blog further on aims and objectives. However, I’d first like to consider for whom these objectives are being undertaken. The disease group primary immune deficiency (PID) includes a vast number of conditions, all of which by have a non-external (ie. genetic) cause. Usefully, they can be summarised in five broad classes:

• B-cell disorders
• Combined T- and B-cell disorders
• Phagocytic disorders
• Complement disorders
• Diseases with current fever and inflammatory manifestations

(For more information on these see IPOPI.)

Whilst some of us require antibody replacement therapy, some of us have much more complex needs; some of our therapeutic needs are life-long and some are short-term; some of us have scheduled periodic therapy, some of us occasionally need immediate urgent treatment. Representing such diverse clinical needs is itself a massive challenge which needs consideration. Whilst condition-specific groups can keep issues on the agenda, we also have to ensure that this occurs without the exclusion of conditions unrepresented by groups.

But we are diverse beyond the range of conditions we have. We are male and female; young, middle-aged and older; from a range of racial and ethnic backgrounds; a mix of gender and transgender roles; gay, straight, bisexual and asexual; single, coupled, married, civilly partnered, divorced; parents, soon-to-be-parents and not parents; a range of positions on with systems and beliefs; different physical and intellectual abilities; and a mix of educational levels, class backgrounds and employment.

In short, we patients cannot be reduced to a single stereotype, and our principle aim has to be empowering all of the patients affected by the condition, putting them at the centre offer objectives. To do this, we have to walk a fine line between representing all those affected and purporting to represent those who wish to distance themselves from our objectives.

People with PIDs are clearly people who should be in “our camp”. However, there is another groups who deserve consideration, those with secondary immune deficiencies (SIDs), which have an external cause.

The best known of these secondary immune deficiencies (SIDs) is probably AIDS (caused by HIV), but other diseases include Good Syndrome, which is functionally the same as CVID, but which is caused by surgical removal of the thymus, and which is treated with IgG replacement therapy. Other causes of SIDs include chemotherapy for cancers, drugs and other diseases which affect organs and tissues related to the immune system, sometimes chronically, but sometimes just in the short term.

So for me a key question which needs to be carefully considered is whether or not we want to include SID patients from the organisation. However, at the same time, I would absolutely not want to usurp the work being carried out by AIDS and cancer charities who expertly support their patients.

I think we need to think about what language we choose to use (for example, in the naming of the organisation), especially since the information, support and representation needs of SID patients are in many cases identical to those of us with PIDs, but we need to think about how we those we represent and support, and those we do not. Who should we represent? Should we focus our name on immune deficiencies or primary immune deficiencies?

Another issue is how we represent, at the national level, the mix of needs in different regions, and for that matter how we define regions. Should each region be equally represented in some way, or do we focus on the four nations?

We are sufficiently complex and diverse that how we represent ourselves has to be given careful consideration. If we can’t address this fundamental need, we will be ineffective in many of our endeavours, such as being able to advocate on behalf of patients to government agencies.

I’d love to hear your ideas and opinions on this topic. Please, contribute to the discussion below or if you want to contact me privately, just add a comment and note you don’t want me to approve it!

Representing patients with primary immune deficiencies

I had a really interesting day yesterday in London, at a meeting to consider how to best to replace the now folded Primary Immunodeficiency Association (PiA). It was organised by two professional groups concerned that patients with genetic immune conditions don’t have a voice which is heard nationally. A voice is important because without someone representing us at the policy level our complex needs can be excluded from consideration in key decision-making processes. Establishing a voice is made all the more important by the radical changes being made to the NHS over the next year.

For me a number of key issues came up. The first is that there is a lot of experience and knowledge out there which we need to cultivate, whether it’s condition-specific or locality-based. Condition-specific groups – of which there are a number – understand the impact of particular diseases and syndromes on day-to-day life and offer incomparable emotional and practical support to people with the same diagnosis, or indeed to their families.

Locality-based groups – of which there are fewer, but I think has growth potential – understand the issues faced by people in a given area. Who to contact, what commissioning problems exist, who the specialists are and where to get specialist equipment and supplies if needed.

It would be an unrealistic expectation for a national organisation to develop this type of expertise itself; it would also be a duplication of effort and disrespectful of the efforts of the individual groups. However, at the same time, smaller groups are not able to muster the kind of support and resources necessary to be effective at the level needed to influence governmental bodies, to engage with clinicians and to identify and promote research opportunities. This needs a body which is representative of all the interests, and which commands the respect of patients, agencies and professionals.

This suggests that rather than providing everything, there is need for an umbrella group working at a national level. However, as one of the representative groups pointed out, it’s essential for such a group to reflect all of its constituents, and to remain accountable to them. Regardless of whether a national body is labelled an umbrella group or an alliance or some other word, this accountability is essential, as is respecting the individual groups’ autonomy. This is a key issue which needs careful consideration as we move forward.

Having agreed in principle that a national organisation is a necessary goal, there was a discussion about what the broad objectives such a body might be. It was agreed that there are four principle broad objectives: information, advice and support, policy and representation, research. Some of these objectives, such as advice and support, may also be objectives of constituent groups, but there will likely be aspects best handled at the national level (for example, work) to avoid redundancy of effort. I intend to expand my thoughts on these objectives in further blog posts.

We also discussed a couple of other issues. The one which concerned me the most was how we ensure that any national organisation is truly representative off and responsive to the needs of all of the people affected by primary immune deficiencies. Some people (including me) expressed concern that some PID patients weren’t aware of the meeting and felt they were being excluded. Whilst accepting that perfect representation is impossible without considering the opinion of every single person (including people who don’t have or want to express an opinion!), it was agreed that a priority for the organisation would be to ensure effective representation, both across demographic and condition groups.

It was then agreed that a number of volunteer patients present at the meeting, including me, would carry the project forward as a steering group, along with representatives from the seven patient groups present at the meeting as necessary. There are also representatives from Northern Ireland and Scotland involved. This will be facilitated by the Chief Executive of Genetic Disorders UK. As part of this process we will be consulting as widely as possible with patients and parents of patients in order to ensure that the finished product meets the needs of as many of us as possible.

There will be a formal consultation, but I would also welcome informal comments, ideas and discussions. You can comment on here, message me on Facebook or ask me to email you in the comments (commenting requires you to have an email so I’ll be ale to reply without publishing either your or my email addresses).

I really do welcome your comments, and for me the highest priority is that the patients and the needs of patients are at the heart of the project. There will also be other people you can contact, and you can also get involved through your patient support groups. If you don’t see your PID patient group below, we also want to hear from you.

• AT Society (ataxia telangiectasia)
• Max Appeal (DiGeorge/22q11.2 deletion/VCFS)
• CGD Society (chronic granulomatous disease)
• HAE UK (hereditary angioedema)
• XLP Research Trust (X-linked lymphoproliferative syndrome)
• UKPIPS (primary antibody deficiency and other primary immune deficiencies)
• Genetic Disorders UK (genetic disorders and runs Jeans for Genes)

All-in-One Prophylaximagic!

I had my six-monthly checkup with my immunology insultant consultant last week (no infections to report, trough IgG of 7.5 g L^-1 which is double what it was a year ago). I have common variable immunodeficiency, a genetic condition which means I don’t produce antibodies, so untreated I can get frequent and repeat infections.

We were reviewing my treatment plan, and discussing that I’ve now been on prophylactic antibiotics for six months. The antibiotic of choice at my hospital is azithromycin, a member of a family of antibiotics called macrolides which also includes erithromycin and clarithromycin.

Molecular structure of azithromycin. Note the large ring in the top left of the image. Thanks to Wikimedia

Molecularly, macrolides are characterised by having a ring of 14 or more (mainly carbon) atoms, making them quite large. As a comparison, benzylpenicillin has 16 carbon atoms in total and a molecular mass of 334.4, whilst azithromycin has 38 carbon atoms and a molecular mass of 749.0, more than twice the mass.

Pharmacologically, macrolides block protein synthesis in bacteria. All cells (and bacteria are just cells with a thick wall) depend on constant replacement of their proteins, so blocking their manufacture kills bacteria rapidly.

Macrolides also have a cunning trick of getting to the bacteria. Neutrophils, a type of white blood cell which is attracted to infections sites, transport as much of the macrolide molecules as possible in the cell. Once neutrophils find the infection, they release bomblets of anti-bacterial chemicals along with the antibiotic. The net effect is they get to the bacteria very quickly and if the chemical warfare from the neutrophils doesn’t kill them off, the macrolides soon do.

However, macrolides are not a one trick pony. In addition to being efficient killers, they also have other beneficial effects, in particular being potent anti-inflammatories. Unlike common anti-inflammatories like ibuprofen, which have a single mode of action, macrolides are multi-modal and suppress inflammation in multiple ways.

One trick they have is protecting the body from the damage caused by the neutrophil attack chemicals. Another trick, also associated with neutrophils, is that they may promote the migration of the chemical warfare specialists to the infection sites, meaning more of them get to the infection, and they get there faster.

They have also been implicated in suppressing expression of endothelin-1. ET1, as it’s known, is a powerful vasodilator which promotes blood flow in the area around an infection, and is what causes infected wounds to go characteristically red and inflamed. In addition, macrolides have been associated with reduction of other signalling chemicals, cytokines and interleukins, which promote inflammation.

These effects have been shown to be beneficial, particularly in a range of respiratory conditions. This includes asthma, particularly where the patient is sensitive to environmental irritants such as dust, and a condition called diffuse panbronchiolitis (DPB). DPB is characterised by extensive bacterial infection in the lungs, and constriction of the airways in response. Treatment with macrolides has increased survival rates from around 50% to better than 96%, with it’s effects exceeding that of an antibiotic alone.

Whilst macrolides become concentrated in normal cells, they aren’t transported into the space in the lungs where air exchange occurs, the bronchial tree. However, they have been shown to have benefit on the lung function tests of patients with bronchiectasis and cystic fibrosis, not by directly affecting the flora, but by decreasing inflammation and promoting the migration of neutrophils. In addition, macrolides may have benefits in atheroma (fatty arteries, which have a strong association with serious and fatal heart disease), arthritis and some forms of cancer.

For those of us who do have poor immune systems, just reducing the bacterial infections is great, but reducing the inflammatory response is a buy-one-get-one-free bonus. So, here’s to an amazing group of drugs that’s making my life more liveable.