Archive for the ‘bronchiectasis’ Category
revisiting bronchiectasis
A couple of days ago I had a minor operation on what the specialist (pulmonologist) described as a partially collapsed lung, which sounded rather serious. It certainly impressed others when I mentioned it. I was diagnosed with bronchiectasis more than a decade ago, and I wrote about it at the time, but I can’t be bothered looking it up so I’ll start again.
Bronchiectasis is – at least I thought it was – a kind of damage to the walls of the many tiny airways in the lungs. Those airways become loose and distended, creating cul-de-sacs which collect bacteria. Think of it as a kind of bend in a creek which collects stagnant, smelly water. Not flushing properly. So the affected part of the lung carries a high bacterial load which means a lot of sputum is produced and the victim tends to have a lot of bacterial infections. I also cough a lot, especially in the mornings.
But – and this I think is new to me – bronchiectasis is also an auto-immune disease – and there’s apparently an effective treatment in the offing. I had an interview with the pulmonologist a few days before my op, and he told me he’d just come back from a conference in Tokyo, as you do, at which this treatment was touted. He didn’t go into detail, so I looked it up.
Pulmonary macrophages, neutrophils and Brinsupri, the trademark name for brensocatib, the first ever FDA approved treatment (in August 2025) for non-cystic fibrosis bronchiectasis (NCFBE)…
A PubMed article published in September has this to say in its abstract:
Bronchiectasis is a chronic airway disease marked by irreversible bronchial dilation, persistent cough, and recurrent infections. Its pathogenesis is explained by the “vicious cycle hypothesis,” which involves impaired mucociliary clearance, neutrophil activation, and tissue damage from neutrophil serine proteinases (NSPs). In August 2025, the FDA approved Brensocatib, a selective dipeptidyl peptidase-1 (DPP-1) inhibitor, as the first disease-modifying therapy for bronchiectasis. By blocking NSP activation, Brensocatib reduces inflammation and exacerbation. WILLOW and ASPEN trials demonstrated significant improvements in exacerbation rates, lung function decline, and exacerbation-free survival, establishing a novel therapeutic paradigm for this previously undertreated condition.
So bronchiectasis is an auto-immune disease, in which the over-active production of neutrophils, the most common type of white blood cells, causes ‘unnecessary’ inflammation – or more specifically, the overproduction of NSPs by those neutrophils.
So how to write about this without getting too technical and confusing myself? So there’s clearly a type of bronchiectasis associated with cystic fibrosis, which I’m tempted to explore, but maybe another time. For the rest I’ll obviously be relying on professional sources, referenced below. My type of bronchiectasis is characterised by ‘permanent airway damage, mucus build-up, and frequent chest infections’. This new medication ‘targets one of the causes of inflammation in bronchiectasis, rather than just treating the symptoms’. It inhibits DPP1 (dipeptidyl peptidase 1), an enzyme, or protein, which activates these NSPs – sometimes too much. Over-activity damages lung tissue. So the blocking of this enzyme reduces the inflammation and the damage.
So an obviously interesting question for me is – why do some people get this over-active response by the DPP1 enzymes? Well, here’s what AINL (artificial intelligence never lies) says on this very topic:
An “over-active response” by Dipeptidyl Peptidase 1 (DPP1) enzymes is not typically a result of the enzyme itself being overactive, but rather a reflection of underlyingchronic inflammatory diseases that lead to excessive neutrophil activity and the release of mature, active DPP1. The enzyme itself is often present in high amounts in the sputum and airways of affected patients, correlating with disease severity.
References
https://pubmed.ncbi.nlm.nih.gov/41180673/
Brensocatib: Is this breakthrough a Game-Changer for Bronchiectasis?
https://emedicine.medscape.com/article/296961-treatment#aw2aab6b6b1aa?form=fpf
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exploring my condition: bronchiectasis with a side of otitis media
grommets galore
Seventeen days from now I will be talking to an audiologist (at last), because my hearing problem (my voice echoing in my left ear, with general hearing via that ear greatly diminished), which was, it now seems temporarily, fixed via an operation some fifteen months ago, has come back. My right eardrum has a sizeable hole in it, so my left ear has long been my ‘good ear’.
The operation, in February-March of 2023, was to place a grommet in my tympanum, to drain fluid from the middle ear region. It’s a relatively common procedure, performed under general anaesthetic, called a myringotomy. The condition is generally called glue ear (due to the viscous nature of the fluid), and usually occurs in childhood, as a result of the middle ear infections (otitis media) common during that period.
For me, the operation was successful, with normal hearing (for me at least) restored more or less immediately. But after coming down with a cold about six weeks ago, which has left me with a persistent cough and a constant need to clear my throat, the left ear problem has returned, with a vengeance. This has made simple conversation difficult to hear, and has had an isolating effect. My chronic condition, bronchiectasis, which is incurable, and which was diagnosed back in 2011, from memory, has added to my woes. A course of antibiotics has had no effect, nor has the regular taking of Bisolvon chesty forte tablets:
For use as a mucolytic to break down mucus and help clear the chest in conditions accompanied by excessive mucus secretions, such as in the common cold, …
– that’s according to HealthDirect, a government website.
I’ve been sucking on Strepsils, claimed to relieve coughs and to soothe sore throats. Surprisingly, my throat isn’t particularly sore in spite of incessant throat clearing, and my voice ‘catching in my throat’ often when I try to speak. I find that I have occasional prolonged coughing fits at night (in bed). I also suck regularly on Eclipse mints, as I assume my breath must be foul.
The ear, the nose and throat are clearly seen as connected, which is why we have ENT specialists, but I feel the need to learn more about the connections in my case. One of my major symptoms is autophony, my voice being loud inside my head, though according to others I’m speaking more softly, if anything. However I don’t particularly hear my breathing, or arterial noises (that would be scary). I do suffer from tinnitus occasionally.
And then there’s the bronchiectasis. I’ve written about this before, but here’s the basic low-down:
It is a lung disease with enlarged airways that are thickened and/or scarred. This can cause mucus to build up in the lungs. Excessive mucus build-up in the airways may lead to repeated infections causing more lung damage.
This is my worry, that the condition has worsened. I was diagnosed in 2011, from memory, and felt at the time that this might shorten my life, but was assured that the condition was manageable and far from fatal. And for a long time after the diagnosis I suffered no particularly serious symptoms.
Last year’s surgery seems to have gone well, and I was led to believe that the grommet would work itself out over time. HealthDirect has a useful video on grommet insertion, and I’ve found a range of grommet pictures online. They range from black presumably rubber rings, which look like tiny car tyres, to your top-of-the-range solid gold versions (bling, but not showy). The video is accompanied by this commentary:
Your surgeon will make a small hole in the eardrum. They will then remove any fluid by suction. This is called a myringotomy. After the suction, your surgeon will place a plastic or metal grommet in the hole. The choice of material depends on how long the grommet will stay in place. Your surgeon will discuss these options with you before your procedure.
This is interesting. My surgeon didn’t discuss any options with me, but if he had, I would’ve opted for the car tyre, because I think we both assumed that this was a one-off problem, but this outcome has changed my mind. I’m assuming that the more solid grommets would stay in place for longer, perhaps even permanently. So….
Last year’s operation wasn’t cheap for this impoverished pensioner, and another such operation would be at least as much, with extra for the bling, but if it fixes that problem permanently, I’ll definitely go for it.
So there’s only the throat problem to solve….
There are different types of bronchiectasis (this is news to me):
Healthcare providers categorize bronchiectasis based on what the damage to your airways looks like — cylindrical (or tubular), varicose or cystic. Cylindrical bronchiectasis is the most common and least serious form of bronchiectasis. Cystic bronchiectasis is the most severe form. Providers also categorize bronchiectasis as focal (in one area) or diffuse (in many areas throughout your lungs). Traction bronchiectasis happens when scarring in your lungs pulls your airways out of shape.
So now I have to find out my type of bronchiectasis, and all I have to go on is an x-ray which seems to show blockage in the upper left lung region, suggesting it is (or was) focal rather than diffuse. My throat-clearing and coughing is now worse than it has ever been, so the condition may be spreading, and another X-ray may be required.
So that’s the sorry situation as it stands. I’ll no doubt return to this topic in the next month or so.
References
https://www.connecthearing.com.au/blog/hearing-and-hearing-loss/middle-ear-infection-otitis-media/
https://www.healthdirect.gov.au/grommets
https://my.clevelandclinic.org/health/diseases/21144-bronchiectasis
a bonobo world? an outlier, but also a possibility: 1
bonobo togetherness – who are the girls and who are the boys?
I’ve decided to focus on this very broad topic, and to write a book. Here’s my first (and in parts my second) draught
Introduction – a slow-burning inspiration.
In these few introductory pages, I’ll be writing a little about myself, after which I’ll (try to) leave me behind. At least as a topic. Of course, I’m on every page, as is Max Tegmark in Our Mathematical Universe, or David Deutsch in The Beginning of Infinity, or Johann Noah Harari in Homo Deus, or any writer of any other book of ideas, but in this opening I want to admit the lifelong passion I have for the set of ideas, or really feelings, I wish to explore here. They’re vital feelings, and big ideas, though they may come out as inchoate, or incoherent, in the telling. I probably feel most passionate about them because they seem so knocked about and pushed aside by the world I find myself in – though that world is always in flux and there are moments of inspiration.
It was in the mid 1980s that I first heard about bonobos on an episode of The Science Show, still running on Australia’s ABC Radio National. I would have been in my late twenties, just beginning an arts degree as a ‘mature-age student’ at Adelaide University. I was living in a chaotic share-house amongst students, student-types, misfits like myself. It had been my life for several years. Due to difficult family circumstances I’d left school at fifteen, and I’d fantasised for a while about being a complete auto-didact, the smartest fellow without a tertiary degree on the planet, or at least on the street, but I was frankly embarrassed at my poverty and my string of unpleasant and failed jobs in factories, offices, restaurants, and briefly, a hospital. My great solace, my way of maintaining pride in myself, was writing. In those pre-computer days I filled up foolscap journals with crabbed writing in blue ink. I wrote about the books I read, the people I met, imitations of favourite writers, and, too often, reflections on the women I came into contact with – admirable, mysterious and ever-unattainable. I still have those journals, mouldering in old boxes, covering 13 years or so before I could buy my first computer.
I was ever a hopeless case when it came to the opposite sex. It wasn’t quite that they all despised or were indifferent to me. I sometimes made female friends but they were never the ones I was attracted to. In fact I rarely made friends, and my obsession with writing didn’t help. As one of my housemates once bluntly told me ‘you’re always living alone no matter how many people you’re sharing with.’
So I wrote about my failures with women and congratulated myself on my literary abilities. I was of course my own worst enemy in these matters. Whenever a woman I was interested in showed signs of repaying that interest, I ran the other way, figuratively and sometimes even literally. There were all sorts of excuses, even some good ones. I was perennially penniless, I had a chronic airways condition – bronchiectasis – that meant my voice would get caught in the ‘wet webs’ as I called them, which made me naturally anxious about my breath, and there were other problems I’d rather not go into. In fact I was intensely shy and self-conscious, but good at putting on an air of intellectual disinterest. This had generally disastrous consequences, as when I encountered a female ex-housemate and told her that now our share-house was all-male. ‘Oh yes, that would suit you perfectly,’ she said with some disdain. I was mortified.
In fact I was obsessed to what I considered an unhealthy degree with women and sex. My fantasies went back to pre-adolescence, when I imagined doing it, whatever it might be, with every attractive girl, and boy, within my purview. Now I assume this was relatively normal, but I’m still not sure. But my thoughts on sexuality and gender went further. I recall – and all memories are unreliable, as they share most of the same neural processes as our imaginations – standing during assembly with my classmates, looking up and down the class line, assessing their attractiveness and overall likeability. It occurred to me that the most ‘interesting’ boys were girlish and the most interesting girls were boyish. I remember being struck by the thought and how smart I was to think it. I returned to this thought again and again.
Before I ever had a girlfriend (and yes I did have one or two) I imagined an ideal, embodied by one of the pretty ones around me, with another brain inserted, more or less like my own. Someone funny, thought-provoking, inspiring, freewheeling, exhaustingly fascinating – and yes, I really did think of myself that way. And yet – I did worry that I might not be able to hold onto such a scintillating prize. And that set me thinking – such an extraordinary girl couldn’t be mine, or anyone’s. She would own herself. To maintain her interest in me, I’d have to be constantly proving myself worthy, which might be a thrilling challenge, and a great motivator. But what if I had to share her? My adolescent answer was – so be it. The key, if I found her so valuable, so inspiring, would be not to lose her. Not to be cut off from her. To prove myself so valuable that she wouldn’t want to lose me either, while seeking out others.
I won’t pretend that they were so clear-cut, but these were certainly the sorts of ideas swirling around in my head when I thought about love, desire and relationships as a youngster, and they hadn’t changed much – perhaps due to little actual experience – when I listened to the scientist extolling the lifestyle and virtues of our bonobo cousins many years later. I still remember the warm tones of his signing off – ‘Long live bonobos – I want to be one!’
So the following is an exploration of a world that seems worthy of study both for itself and for ourselves. We’re now the overwelmingly dominant species on the planet, and this is having strange contrasting effects, of hubris and despair. It’s also the case that we’re not one thing – our species is composed of cultures that seem to have little connection with each other, and multiculturalism is seen as having enriching as well as disastrous consequences. In such complex and dynamic circumstances, what do bonobos really have to teach us? The following is an attempt to answer that question in the most positive light.
covid19: monoclonal antibodies, symptomatic v asymptomatic, corticosteroids, comorbidities
keeping it simple, for now
Jacinta: Let’s look at monoclonal antibodies briefly before we continue with those medcram updates. Francis Collins, the somewhat controversial but scientifically reliable directer of the NIH in the USA, recently described ‘monoclonals derived from people who’ve survived covid19’ as the best hope for treatment in the absence of a vaccine. So what are these monoclonals? There are lots of useful videos on youtube that provide detail. I’m picking one from the JAMA network. The technology for producing these types of antibodies was developed in the mid-seventies. It was called ‘murine hybridoma’ technology, murine meaning ‘mice’. I remember first reading about monoclonal antibodies in a Scientific American article in the early eighties. It went straight over my head of course, but now it’s time to get a grip on them. So mice were injected with an antigen, which in general terms is a pathogen that induces an immune response. In more specific terms an antigen is a molecule or structure, part of a larger pathogenic molecule, that can be bound to by an ‘antigen-specific antibody’ or B cell receptor. B cells are lymphocytes that secrete antibodies. So the researchers induced this response, then isolated B cells from the spleen of the mice, which they fused with myelomas (cancerous plasma cells). Cancer cells are notoriously long-lived – see ‘the Immortal Life of Henrietta Lacks’ – so these fused cells, called ‘hybridomas’, act like B cells in producing antibodies, and like tumour cells in their ability to replicate. So these hybridomas can be grown in culture and each one can produce a single antibody type, which targets a single antigen type. Hence monoclonal. They can clone themselves for a specific antigen. So, once you know your antigen, you can create a ‘monoclonal’ specifically for it, or two or three to choose from. And now, with covid19 and with technological development, we can isolate monoclonal antibodies not from mice but from recovered covid19 patients. So that’s a somewhat over-simplified account – for more detailed info on monoclonal antibodies, this zero to finals video is excellent, and there are doubtless others. The target for this work is generally the S-protein of the SARS-CoV2 virus, with various particular sites being looked at, and a number of teams working on the research. Some are pretty well ready to go, with specific antibodies or sets of antibodies. The argument is that they could be used for high-risk groups such as ICU workers and nursing home clients, as a kind of temporary vaccine.
Canto: Okay, something else to keep track of. So update 93 discusses an article published in Nature Medicine – all the authors appear to be Chinese – which looks at 37 asymptomatic covid19-infected subjects and their antibodies, compared to those of 37 symptomatic subjects.
Jacinta: So they looked at their immunoglubulin G (IgG) levels. These are the most common types of antibody, created and released by plasma B cells. They graphed the IgG during the acute and convalescent phases, and they defined the acute phase as that in which the viral RNA was detectable in a respiratory specimen, and the convalescent phase as from eight weeks post-release from hospital. What the graph shows is that the IgG levels decreased from acute to convalescent in both symptomatic and asymptomatic cases, but more in the symptomatic cases. They also looked at ‘neutralisation rates’, which presumably refers to the effect of antibody activity. A positive effect means more neutralising antibodies are produced. These seemed about the same between the phases for both groups, but another graphic shows that in the convalescent phase, the symptomatic group have substantially more neutralising antibodies. It seems from this admittedly small study that asymptomatic subjects are at risk of reinfection, after a period of time.
Canto: And even symptomatic subjects after recovery, as we have obviously no longitudinal studies on anti-viral IgG levels, as the study points out.
Jacinta: Well that takes us to the next study, from Spain, which managed to round up almost 52000 participants. The study tells us between late April and mid-May the estimated seroprevalence (the percentage of inhabitants that had the virus) for the whole country was around 5%, depending on different test types and results, and with great variation between regions. Findings were that prevalence increased with increasing age. Looking at different jobs, those working in healthcare were clearly more at risk, and to a lesser but still significant degree, those working in nursing homes…
Canto: Which is still largely healthcare, but less trained, and often less prepared for this onslaught…
Jacinta: Point taken. And those living in the larger municipalities were more often infected than those in less densely populated regions. Interestingly, they found that the rapid (and cheap) fingerpoint test, which provides results within ten minutes, was pretty close to being as effective as an immunological assay, which is important as the delay in test results has been a major issue.
Canto: Amazing. Why aren’t they using this all the time? Everywhere?
Jacinta: That’s another issue – maybe later. Anyway, much of this study confirms the many smaller studies that have been conducted. They found that healthcare workers comprised 24% of all confirmed cases. This may be partly because they had more access to testing. There is so much to glean from this study, I can only skim. But here are some very interesting remarks in their conclusion:
One in three infections seems to be asymptomatic, while a substantial number of symptomatic cases remained untested. Despite the high impact of covid19 in Spain, prevalence estimates remain low, and are clearly insufficient to provide herd immunity. This cannot be achieved without accepting the collateral damage of many deaths in the susceptible population and overburdening of health systems. In this situation, social distance methods and efforts to identify and isolate new cases are imperative for future epidemic control.
Canto: So there are no easy solutions, and even a vaccine is not necessarily going to be the magic bullet everyone’s hoping for. The proof of the pudding will be in the eating, and we haven’t eaten any vaccines yet. They won’t be on the menu for a while, and it’ll be a lot longer before we can gauge their nutritional value.
Jacinta: Yes, what you’re saying is, we don’t know how long antibodies to this virus will last. We’re still in unexplored terrain with respect to this very unusual and deadly virus. An article published on the Jama Network quite a while ago is still relevant now in its conclusions, as nothing we’ve so far found disconfirms it:
… the immune response to covid19 is not yet fully understood and definitive data on post-infection immunity are lacking. Amidst the uncertainty of this public health crisis, thoughtful and rigorous science will be essential to inform public health policy, planning and practice.
Canto: Frustrating to many. So with update 94 we’re getting towards mid-July and they’re noting that things are hotting up, as the weather is cooling down, in Australia, though of course it bears no comparison to the US tragedy. They were talking about things getting worse in their autumn, but summer hasn’t given them any sort of break.
Jacinta: So update 94 first looks at inhaled corticosteroids, one of many medications being considered and perhaps used by health professionals, others being ivermectin (a broad-spectrum anti-parasitic drug) and nitric oxide, all without solid RCT-type evidence. Even so, case reports and other low-level studies show promise, and these are arguably desperate times. A study presented by Dr Seheult suggested that some corticosteroids showed positive immunological effects in case reports and in vitro. Interestingly, asthmatics have been prescribed corticosteroids quite regularly…
Canto: As have I, from time to time. At least I think it was corticosteroid…
Jacinta: Well, that’s interesting, I know you’re not asthmatic but with bronchiectasis you have asthma-like symptoms at times. And the good news for you, and generally interesting news for us all, is that ‘asthma patients with covid19 do not appear to have a higher rate of hospitalisation or mortality compared with other covid19 patients’. Indeed it may be the opposite, as data from Wuhan indicates that less than 1% of their hospitalised patients had asthma, compared to 5% in the general population. In New York, too, asthma wasn’t even in the top ten comorbidities, which is pretty striking for a virus that hits the lungs first. Similarly, COPD, which your ailment is surely associated with, comes in below diabetes, renal disease and a whole range of cardiovascular issues as a comorbidity factor. A possible reason for this is that the kind of chronic inflammation produced by asthma and COPD is associated with reduced ACE2 expression, meaning fewer receptors for the virus. So these conditions could actually be protective. And they might also be on corticosteroid inhalers, which may also be protective.
Canto: That sounds great. Let’s leave it there before I hear any bad news…
References
Coronavirus Pandemic Update 93: Antibodies, Immunity, & Prevalence of COVID-19 – New Data from Spain
Coronavirus Pandemic Update 94: Inhaled Steroids COVID-19 Treatment; New Pneumonia in Kazakhstan?
How do monoclonal antibodies work? Rituximab, infliximab, adalimumab and others
Coronavirus Treatment and Prevention with Monoclonal Antibodies
Covid 19: corticosteroids, inflammatory markers, comorbidities
Canto’s bronchiectasis – a relatively mild case, thank dog
Canto: So update 87, in late June, reflects a period when daily cases were just starting to rise, but deaths were apparently reducing – and various reasons were being given for this.
Jacinta: And interesting to note all the skepticism around Oxford University’s dexamethasone trial, which has led (the trial, not the skepticism) to a huge demand for the steroid. Dr Paul Sax of Harvard Medical School has expressed some dismay at the negativity, as this was a randomised controlled trial (RTC) of a widely available drug by a highly reputable, government-funded institution.
Canto: Yet it seems that the website on this trial has since been taken down, so maybe there are some issues…
Jacinta: Okay, so let’s move on. Dr Seheult talks about raised ‘inflammatory markers’ in patients he observes coming in with covid-19. He names them, and I want to do a shallow dive into what they are and what they mean: Ferritin, C-reactive protein (CRP), CPK (to do with muscle breakdown), erithrocyte sedimentation rate (ESR), and d-dimer levels. So, ferritin is an iron-containing protein. It stores the iron and releases it when needed. Ferritin is mostly concentrated in the liver cells (hepatocytes) and in the reticuloendothelial cells of the immune system. That endothelial word again. As for CRP, this abstract from a 2018 paper Frontiers in Immunology tells me that ‘C-reactive protein (CRP) is an acute inflammatory protein that increases up to 1,000-fold at sites of infection or inflammation….CRP is synthesized primarily in liver hepatocytes but also by smooth muscle cells, macrophages, endothelial cells, lymphocytes, and adipocytes’. Need I say/quote more? And on CPK, this from the Johns Hopkins Lupus Center:
Creatine phosphokinase (a.k.a., creatine kinase, CPK, or CK) is an enzyme (a protein that helps to elicit chemical changes in your body) found in your heart, brain, and skeletal muscles. When muscle tissue is damaged, CPK leaks into your blood. Therefore, high levels of CPK usually indicate some sort of stress or injury to your heart or other muscles.
And the US website medicineplus.gov has this to say on ESR:
An erythrocyte sedimentation rate (ESR) is a type of blood test that measures how quickly erythrocytes (red blood cells) settle at the bottom of a test tube that contains a blood sample. Normally, red blood cells settle relatively slowly. A faster-than-normal rate may indicate inflammation in the body.
So, a fast ESR is an inflammation marker. High levels of CPK in the blood are too, presumably, as are high levels of CRP, wherever. And ferritin. Lastly, d-dimer levels, which are also related to clotting. This Australian site, healthdirect, tells me that ‘D-dimer is a type of protein your body produces to break down the blood clot’. So, a d-dimer test is ‘a blood test usually used to help check for or monitor blood clotting problems. A positive test means the D-dimer level in your body is higher than normal and suggests you might have blood clots’.
Canto: With all that let’s continue with the update. In Seheult’s hospital they started using dexamethasone as soon as the Oxford results came out and they’ve seen a reduction in all these rising inflammation markers. He recognises issues here though. Is this just anecdotal? Is this just a drop in the markers without real-life effects? Could it be recall bias? We know how conveniently inaccurate memory can be.
Jacinta: My impression is that’s not going so well, though there’s no doubt still a varied use of dexamethasone and other corticosteroids throughout the USA. We’re at the point with the updates where they’re still thinking deaths in particular are reducing. We now know better. So the update next looks at a Chinese study from mid-June entitled ‘clinical and immunological assessment of asymptomatic SARS-CoV2 infections’. This small study looked at 37 asymptomatic patients and found that viral shedding (the release of virus from an infected person into the environment – the period of contagiousness) was 19 days, presumably on average. This compared with 14 days for symptomatics. A pretty significant finding. Immunoglobulin G (IgG) levels – essentially antibodies – were about six times higher in the symptomatic cases. That seems unsurprising I think, because it’s the antibodies that largely create the symptoms – the inflammation and clotting, the cytokine storm. Another finding was that, eight weeks after being discharged from hospital, the asymptomatic cases were 40% seronegative (having no antibodies) against SARS-CoV2, compared to 12.9% for the symptomatic cases. This suggests that neutralising antibodies may be ‘disappearing’ over time, though other immune cells, such as T cells may have a mitigating effect. Overall, though, the study advises extreme caution:
Together, these data might indicate the risks of using covid19 ‘immunity passports’ and support the prolongation of public health interventions, including social distancing, hygiene, isolation of high-risk groups and widespread testing.
Canto: Not suggestions the current Trump administration would be likely to pay attention to.
Jacinta: Well the question here is one of re-infection, and I don’t know if there are any clear answers to that. Anyway update 87 goes on to look again briefly at vitamin D, and research in the UK, where vitamin D deficiency is more of a problem, and is associated with viral chest infections and with covid19 outcomes, with people of colour being disproportionately affected. They’re looking to people to sign up with a study called ‘covidence UK’. Dr Seheult also looks at a ‘Research Letter’ from the JAMA network entitled ‘prone positioning in awake, non-intubated patients with covid19 hypoxemic respiratory failure’. Prone positioning – lying on your tummy – was highlighted in one of the earliest of these covid19 updates as improving the symptoms of patients with ARDS. The findings from this JAMA are instructive:
In this small, single-centre cohort study, we found that the use of the prone position for awake, spontaneously breathing patients with covid19 severe hypoxemic respiratory failure was associated with improved oxygenation. In addition, patients with an SPo2 [pulse oximetry, a measure of blood oxygen level] of 95% or greater after one hour of the prone position was associated with a greater rate of intubation.
So, though there’s a need for RCTs etc etc, Dr Seheult has found dramatic improvements in oxygenation in his own patients through prone positioning.
Canto: Who are we to argue? And this update 87 ends on a positive note due to these combined findings about treatment. Prone positioning, remdesivir, dexamethasone, vitamins D and C, zinc, and maybe convalescent plasma, which needs to be explored further..
Jacinta: That’s blood plasma from recovered covid19 patients, with of course the antibodies to go with it, and I’ve looked at the National Covid19 Convalescent Plasma Project website to see if there are recent studies on this, but there’s nothing since March – small studies from China, which seem promising.
Canto: Update 88 starts again with dexamethasone, the cheap and widely available steroid, which – and this is back in late June – the British government got behind after the Oxford study was published, authorising its use ‘for patients hospitalised with covid19 who required oxygen, including those on ventilators’. It’s interesting that clinical views have changed on corticosteroids for covid19 over time, and there are still concerns about dosage and time periods on the drugs.
Jacinta: Yes, short courses of corticosteroid treatment seem to be recommended, and not just dexamethasone. And many studies showed this before the release of the Oxford data.
Canto: So the Oxford data itself is fascinating, especially for comorbidities or previous conditions. Especially interesting to me as I have such a condition, one that fits under their heading ‘chronic lung disease’, in my case bronchiectasis. They’re finding that people with such conditions are ending up on ventilators far less than those with diabetes or heart disease. So that’s good news for me. The disease, as they’ve been finding, is that covid19 is essentially an inflammatory disease of the vascular system. However, it seems that Dr Seheult’s hopes, at the end of update 88, that the greater introduction of short-term corticosteroids, and the use of other medications that might be efficacious, would reduce the mortality rate, have been dashed. We’ll be interested to find out why in upcoming posts.
References
Coronavirus Pandemic Update 87: More on Dexamethasone; Do COVID-19 antibodies last?
Coronavirus Pandemic Update 88: Dexamethasone History & Mortality Benefit Data Released From UK
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908901/
bronchiectasis once more – resistance, viruses, treatment
Having fallen ill again, for the first time really in a few years, with debilitating dry coughing, breathing problems and fatigue, and having had no great relief from a first course of broad-spectrum antibiotics, I think it’s a good time to review the condition I suffer from – bronchiectasis.
I’ve tried to put it in the back of mind and have been mostly successful, except now and then to marvel that it hasn’t come roaring back for a year, then two years, then three years. Still, I’ve never quite gotten rid of a niggling cough, and every time I have a sneezing fit my mind turns, however briefly to what might finally await me…
Bronchiectasis literally means ‘widened or widening airways’. The airways leading to the lungs have become permanently distended and develop ‘cul de sacs’ in which bacteria gather as in a stagnant backwater. The increased bacterial load means that those with the condition are easier prey for bacterial and viral pathogens. The causes of this condition are various, including genetic conditions such as cystic fibrosis, or a general immunodeficiency. In my case it was most likely an early childhood infection, the cause in about a third of all adult cases. The sad thing is that with each new flare-up the damage to the airways is increased, the condition worsens, and there’s no cure, but it can be contained through specific exercises designed to clear the airways, postural drainage and other techniques. Above all (he adonishes himself) always get regular flu and pneumococcal jabs. I was diagnosed with this condition about four and a half years ago, but I think I’ve been suffering from it for much longer. Like many stupid men I’ve tended not to go to the doctor till I’m at death’s door. I’ve improved a little in that area in recent years, but not enough.
The recent flare-up has been traced to a relatively common virus, called respiratory syncytial virus (RSV). My doctor sent me for a virology swab after my second visit. On my first visit I presented with my severe cough, and I explained my bronchiectasis, which he knew something about as I’d had my records transferred to him from a previous establishment. Although I expressed concern about antibiotics, having experienced what I presumed to be resistance to erythromycin previously, I was prescribed a broad-spectrum antibiotic called roxithromycin GH. Desperately wanting to get rid of this debilitating and spirit-weakening cough, I got the set of ten tablets – a five-day dose – together with a repeat dosage. I’m currently two tablets away from finishing the repeat. It was also recommended that I get a bottle of Bisolvon®, which ‘thins, loosens, clears mucus from the chest’ and ‘helps clear stubborn chest congestion’.
This first consultation was on a Friday. I was contracted for a two-day work week at Eynesbury College starting the following Thursday, and I really wanted to be fit by then. However, by Monday-Tuesday I was worried. The antibiotics, I felt, had been initially successful but then my condition seemed to deteriorate. On Wednesday I had my second consultation. I explained my amateur theory that the antibiotics had an immediate impact, but then the resistant strain of the bacteria continued to multiply, took over the territory of the non-resistants, and the illness came sweeping back. Classic evolution, in a sense: from random variation the environment of my body selects the stronger, resistant strain. The doctor agreed, or said he did, but pointed out that the problem was that my infection was probably viral rather than bacterial. In my enthusiasm for my own cleverness I hadn’t thought of this. And this probably explained the ineffectiveness of the erithromycin in the past. Maybe I’m not resistant at all.
So I was sent to the nearest Clinical Labs testing centre for a swab. I was also advised to continue with the antibiotics. The swab is applied by means of a long needle-like instrument wrapped in something like cotton wool at one end. This material is soaked in a virus-detecting solution and inserted fairly deeply into the nasal cavity. I visited the testing centre more or less immediately after the consultation, and received word the next day that the results were out. On Friday, I think, I attended my third consultation and was given the read-out. Ten viruses tested for were presented, including influenza A and B, and types 1 to 4 paraainfluenza, all undetected. The other undetected viruses were adenovirus, rhinovirus and metapneumovirus. RSV, an RNA virus (as are most viruses), was the only one detected.
So, progress has been made, and I was prescribed one more medication, a Turbuhaler® called Symbicort®, often used for symptomatic treatment of asthma. Instructions are to inhale two doses a day of the oral powder, which consists of budesonide and eformoterol fumarate dihydrate. There are 120 doses in my inhaler.
Budesonide is a corticosteroid, commonly used in this inhaled form for long-term treatment or management of asthma and COPD. It’s been around for a while, having been patented in 1973, and in commercial use as an asthma medication since 1981. It’s also on the WHO list of essential medicines. According to Wikipedia, ‘common side effects with the inhaled form include respiratory infections, cough, and headaches’, and at the moment I have a headache, and have suffered from severe coughing fits. I’m also producing quite a lot of mostly clear mucus, through the nose. I’ve attributed these symptoms to the virus, not the medication, but who knows?
Eformoterol is a more recent addition to the arsenal of anti-asthma type medications. This 1997 article in Australian Prescriber describes it as ‘a long-acting beta2 adrenoceptor agonist’ – a type of beta-blocker. Here’s some further interesting info from this site:
After inhalation of eformoterol powder, bronchodilatation begins within 3 minutes. This effect lasts for 12 hours with a peak effect within two hours of inhalation. These properties make eformoterol suitable for twice daily inhalation in patients who require regular, long-term treatment of reversible airways obstruction. It is not recommended for use in acute asthma. Patients should have a short-acting agonist, such as salbutamol, available to help deal with acute attacks.
Unfortunately my airways problems aren’t reversible, though particular obstructions and their causes may be treated effectively.
So what I have in my little Turbuhaler is a combo of a corticosteroid and a long-acting beta2 agonist (i.e. a bronchodilator). According to Wikipedia ‘combinations of inhaled steroids and long-acting bronchodilators are becoming more widespread’.
It doesn’t seem as if there’s much I can do but wait for my condition to slowly improve. It’s been nine days since my first consultation, and I’ll be revisiting my doctor in a day or two. Mucus still flows freely and the distinctive, whistling wheeze I developed about a week ago is still present (I’ve never experienced this before). Physical exertion quickly makes me exhausted, but I’m hoping I can soon be sufficiently recovered to consider specific exercises to improve my condition and support me against further setbacks. Don’t want to end up slowly drowning in my own phlegm.