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5 Things and a Scoop

3 Jan, 14 | by tomfardon

It’s New Year – Happy New Year, by the way – and the internet is full of last year’s greatest, top 10s of everything from 2013, some top 16s, worst 5 things too, not to mention the all important top 40 countdown (Does anyone else miss Top Of The Pops…), and the even more important 20 words I should avoid in this blog. So, rather than recap 12 months of highs in Thorax, or in respiratory medicine, I’ll try to look forward at the 5 things I’d like answered in 2014. In no particular order…

1. What to do for patients with COPD.
This has to be on everyone’s agenda somewhere, doesn’t it? Sammy Suisa gave us the preview in 2013, but it wasn’t until the end of 2013 that he dropped the full bomb – Canadian COPD patients on Symbicort, and more so Seretide, get more pneumonia, and they die. “But the data is retrospective” (although from an enviably large database, but retrospective non the less) “so is it valid”, say my colleagues. “Where’s the prospective data?”. It’s in TORCH, of course. So job done. “But why do ICS/LABA reduce exacerbations, and” (nearly statistically) “significantly reduce all cause mortality?”, my specialist nursing colleagues ask. And at the ERS in Barcelona, data spewed forth on the “Dual Bronchodilator” approach, novel only because no pharma company has up to this point been able to produce a LABA and a LAMA, but known since 2002 to the jobbing chest physician (Spiriva + Serevent was a common enough prescription in the mid and late naughties, certainly in our practice). There’s even some triple therapy data out there, but it has the big ugly shadow of “the steroid data” looming over it. Ultibro (Which is too close to Ultimo if you ask me) is the first to licence, and the first to market, in the UK at least, yet it will not be promoted, due to cut backs in the primary care division of Novartis. We wait for new molecule, or put our hopes into Roflumilast, or perhaps a resurgence of theophylline. In an area of respiratory medicine that has such a huge evidence base, we are still looking out through a fog of misunderstanding. My take on this is that the big studies done up to this point have not stratified out the patients in any meaningful way; there’s been divisions by FEV1 (Shown nicely by ECLIPSE to have little bearing on exacerbation rate, or anything else, really), or by treatment burden, but no consideration of separating out the “drier” emphysema patients from those will a more productive, “wetter” variants in chronic bronchitis, and what of COPD patients with bronchiectasis. I don’t think we need bigger studies, I think we need smarter studies, with real life phenotypes, putting into studies those patients we actually recognise as being patients we see.

2. What to do with macrolides?
Always on the agenda at bronchiectasis meetings, splitting the audience variably, is the use of long term, low dose, macrolides. Bronchiectasis continues to be the slightly ignored, slightly odd cousin of CF; we get the CF ‘cast offs’. Azithromycin works really well in CF, so why not try it in NCFB?”. The problem is when it really doesn’t work so well – DNA’ase works wonders in CF, works dark magic and mischief in NCFB. So we try, and we dabble, and we see successes, and failures, and try to find our way in a research vacuum that many centres in the UK are desperately trying to fill. Back to macrolides. We’ve all seen them work, I’m sure. We can all recall an unfortunate patient, often young, with recurrent infections, to whom, as a punt, we gave long term clari, only to see them at 3 month review, with a na’er a cough, spit or tickle. And yet, the advice on who should receive it, and indeed which moiety, and what the criteria should be for initiating, and stopping, are wooly, and not well adhered to. At a recent meeting of chest physicians in Scotland, there was no consensus at all on how long a trial of macrolide should be given to a patient with NCFB, with opinions ranging from 6 weeks to a year; some physicians wouldn’t give it at all. So we need a trial, a big trial, a well designed and well co-ordinated trial A multi-centre, UK wide trial perhaps? Certainly there’s a need for it in NCFB, but what of the other diseases? There’s been “macrolide creep” in recent years, creep into asthma, COPD, and anything else that produces exacerbations, infective or inflammatory. The COPD trials show some improvements, but the trials didn’t differentiate between phenotypes, which makes it difficult to know if Mrs Miggins with emphysema, or Mr Melchit with chronic bronchitis are going to react in the same “magic” way. So we give them both a trial, but of which? And what dose? And for how long? And if it works, how long do we continue it? If 2014 provides me nothing else but a clear guideline to follow, backed up by some really good evidence, telling me who and what and how much and for how long, I’ll be a happy blogger.

3. What to do in UIP in the Post-Pather World?
Sounds like a great title for a BTS symposium. I am not an ILD enthusiast. We have an ILD lead, and it’s not me. But I do a remote/rural clinic once a week, and see plenty of ILD, mixed up with everything else. Pre-Panther, it was straightforward enough – have a open and honest discussion with the patient about the risks associated with steroids/azathioprine, and the near impossibility of predicting their prognosis, and the patient chooses, and usually chooses to sit it out. But at least they had a choice. Now, Post-Panther, we have no obvious option. We have pirfenidone – and a handy booklet courtesy of Thorax on the indications for it – but it’s expensive. Massively expensive is something I’m used to, after all I have 3 patients on ivacaftor, and 3 on posaconazole, but I feel I standing on firm ground giving these, and it’s small numbers. A quick calculation on the back of a beermat suggests we probably have hundreds of patients who qualify for the pirfenidone treatment. At an ATS many moons ago, Talmadge King stood up in an ILD symposium (I’m not an enthusiast, but I do try to keep up my CPD). He proposed that the only ‘ethically sound’ management plan for a patient with UIP was to enrol them into a study. There was much wailing, and gnashing of teeth, but in the end, no-one had a better plan. I don’t see we’re much further on. So I’ll keep up my current practice, which is to refer to our enthusiast those who meet the pirfenidone criteria, and keep a list of everyone else…

4. Can someone work out what Sarcoid is?
I see a lot of sarcoid, and I’m not sure anyone really knows what it is, do they? My good friend Wikipedia says it’s probably a lingering reaction to an infection. Patient.co.uk agrees that it’s probably triggered by an infection, in genetically susceptible people, but can’t specify the causative organism. I really like the Royal Brompton’s patient information page on sarcoid; it’s charmingly honest about our lack of understanding of the disease, leaving the patient with “bad luck” as their causative organism. What confuses me, and others I chat to about such matters, is the massive variation in disease severity. Remember at medical school when you were taught that BHL and EN in young people would resolves spontaneously? Remember when revising for MRCP the stats about percentage of patients disease free at 9 years without relapse? I recall the steadily increasing numbers of patients who come up to my clinic on ever rising doses of immunosuppressants, with little in the way of improvement. Patients with complications of steroids that start to outweigh the underlying disorder, and patients who crumble in front of me, as I look on, helpless and slightly embarrassed that we don’t have anything else to offer. It must be more than one disease, right? Surely it’s a spectrum of granulomatous disorders, some of which are exquisitely steroid sensitive, and others that are rampant even in the face of aggressive immunosuppression. Or is it simply that these patients do have an infection. An infection that causes granulomata, that we just simply can’t detect, grow, let alone treat, that immunosuppression is providing jet propelled assistance to, and we’re ‘first doing harm’. Again, I’m not an enthusiast, but I try to keep up – there wasn’t a lot at the ERS about sarcoid, but a quick Google Scholar search (0.05 seconds, if you must know) gives me: CD4 subset dysfunction; pulmonary function tests are more useful than HRCT, or KCO; and early data on exhaled breath condensates in pulmonary sarcoid. The work is going on, but I’d like Santa to let me know what causes Sarcoid in time for Christmas.

5. A Reliable Indicator of Infection…
The Holy Grail? A marker to distinguish between an infective exacerbation, and a non-infective exacerbation of COPD would be very nice, thank you. My next-office-neighbour at work is the professor of infectious diseases, and national lead for antimicrobial stewardship: a way to cut needless antibiotics would be high on his wish list for 2014, I’m sure. I’d like to take it one step further, and ask for something we’re very near to: a practical way to take 16S analysis of sputum/bronchial washings to the clinical environment so we can quantify the microbiological load in the bronchiectatic/CF/COPD lung. We know there’s bugs down there, but are they really the cause of Mrs Miggins’ current admission? IV antibiotics over a 2 week stay in hospital do seem to make our patients feel better, but the physio, hydration and rest they get must have something to do with it, my registrars keep telling me. We’ve started 16S analysis on a research basis, but the information we get from the test needs to reach a clinical audience. I heard a very interesting talk last semester by Prof Colin Palmer, on the GoShare project. the ‘automisation’ of full genome sequencing over the past decade means a sample of blood can be turned into a full genome sequence in a couple of hours, and all for a couple of hundred quid. Understanding the information that’s been handed to you might take a while, but the system delivers information that was beyond our dreams 30 years ago. Back to infective markers, and we’ve had, and continue to use, Pro-Calcitonin, although only in our ICU environment as we’re yet to be convinced. As the theory of the lung being a sterile environment withers on the vine, and we start to understand that infections are a disruption of the balance of microorganisms within the lungs, we need technology like the 16S analysis closer to the bedside. As my neighbour tells me with a face of thunder: “We’re going to run out of antibiotics at the rate you give out Tazocin”

My look forward to 2014 has become more of a review of things I don’t understand, and a wish list for the things I can’t control. But I spared you the Top 10 of Everything.

One final note is to take a look at the Thorax Weekly Scoop.it. “Props” to @DundeePublicH (It’s not just about water) for pointing me to Scoop.it, a site that allows me to grab anything I think is interesting over the week, and put it in “one digital place”. I’ll drag some of it over to here on the Blog, and discuss at variable lengths, and wait for the torrent of discussion to appear in the comments section.

My pick of the Scoops from this week? Will Big Lungs Make You a Better Cyclist?.

Stay classy, internet.

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