Less Streptococcus = More Moraxella

Increased rates of vaccination against Streptococcus pneumoniae in recent years have led to a reduction in the nasal carriage of this bacterium. But the nose is still the nose, and bacteria will be there! One of the bugs that has stepped up to the plate is Moraxella catarrhalis. This organism is assuming increasing importance as both a coloniser of the airways of people with chronic obstructive pulmonary disease (up to 10% of COPD patients are colonised) as well as a cause of exacerbations.

Ah, the unanticipated repercussions of medical advances.

Andrew

Sunny Mildura

We had a great day in Mildura yesterday, Ms Mills and I. Having been reassured by Maurice, our pilot, that the winds were nothing the little Cessna -cabin about as big as Heather's Nissan Micra - couldn't handle, we took of with great enthusiasm. Man, the Western District is wet. Dams are overflowing, rivers are full (Cavendish looked like an island). I enjoyed the view all the way ...to Glenisla, when I decided I should do some journal reading.

Maurice was right. The wind settled down, Ms Mills went to sleep in the back seat and we flew on. And on. This was a little plane, and the flight to Mildura lasted a whole 2.5 hours.

At this time of year, though, the climate up there is enough to make one consider moving. Twenty-two sunny degrees. Shame I had a busy day of patients booked at the Aboriginal Health Cooperative. This time we landed before the Qantaslink flight from Melbourne and, hastening towards one of the two waiting taxis, were whisked to the co-op without delay. Ms Mills was impressed by the fragrantly clean facilities as I enjoyed meeting up with the local staff, who are gradually becoming valued colleagues. All irony aside, they do a fantastic job with extraordinary levels of commitment.

Shame the patients don't always show up. On a day like yesterday, who can blame them? I wouldn't chose to go to see the doctor if the option was to sit soaking up the late-winter, warming sun. They stayed away in droves.

So my favourite Irish nurse, Mrs Mac and I (the three of us. Mrs Mac is not Irish) sat down to hatch a plan. I was greatly impressed that Mrs Mac was keen to push on - in spite of the lack of support from the breathless, snoring coughers in the community to our service. We began to think expansively. Let's open the service up; encourage referrals of non-indigenous as well as indigenous people. Offer what we do to the entire Mildura and regional community from our base at the co-op.

At least that was the gist of it. The conversation was after lunch, so I had to keep notes. Too much sunshine to go with lunch at the Sun Brewery left me struggling to get my head back in the game.

Not Ms Mills though. She cherished a good hour or two castigating my favourite Irish nurse for forgetting the difference between reproducibility and repeatability in spirometry (she likes that kind of stuff) and was on a high when time came for goodbye.

Come three o'clock and it was all over. Ms Mills and I bid farewell, looking forward to returning in a few weeks. As those days get longer we might be able to round off the day with a happy-hour at the Sun. The flight south was a flight back into the rain - over Balmoral and the Douglas mine. Jackets back on, back home.

I love my job.

Andrew

Screening for obstructive sleep apnoea

It took me a little while to get around to opening Sleep Journal from the start of last month, but I have enjoyed reading a study from Japan which validated a simple questionnaire intended to screen a community-based population for obstructive sleep apnoea.

This study group (Sleep Vol 32 No 7 p939-948) created a questionnaire that required only information about a person's gender, body-mass index, snoring history (yes or no) and blood pressure. From this information a score out of 18 was obtained. Scores above 11 were increasingly predictive of the presence of occult obstructive sleep apnoea.

Why did I like this paper?

Firstly, there was no question about sleepiness. Realising that people in the community who have obstructive sleep apnoea may be differentiated from those who go to the doctor with the problem by the absence of sleepiness, this somewhat-nebulous symptom was left out of the mix.

Secondly, a neat combination of two investigations that fall short of a full sleep study was used to evaluate for the presence of obstructive sleep apnoea. A home monitoring device was used which measured only the usual respiratory channels that we measure in the sleep lab - air pressure changes at the nose, thoracic and abdominal elasticated bands as well as pulse oximetery But how did they know when the person was asleep? A wrist actigraph was worn. This is essentially a motion sensor, the size of a wrist watch. When motion stops, sleep is assumed. This sort of device is used in evaluation of people with problems such as shift work sleep disorder, as it is more objective then a sleep diary. The combination of actigraphy and respiratory monitoring is much more simple then a full sleep study. Together they constitute, I think, reasonable way to follow up a community screening questionnaire. There will probably be more of this sort of diagnostic evaluation performed here once medicare agrees to pay for such a test.

Finally, I think we could use something like this here. It should not be difficult to validate for local conditions (our at-risk BMI is likely to be higher than the Japanese). And that has got me thinking ....

Remembering theophylline

My registrar recently asked me why some of my patients with chronic obstructive pulmonary disease (COPD) were on theophylline - the implication being that this is an outmoded drug, and I am an anachronistic practitioner.

Actually, it was put very politely - but the question hung in the air for a moment before I answered.

Theophylline is an old drug - having been used first for the treatment of asthma in the 1950s - which has long been recognised to relax airway smooth muscle. It has retained its place in the treatment of chronic obstructive pulmonary disease over decades. Every consensus statement on the management of COPD includes a place for methylxanthines, which in Australia means either oral theophylline or intraveinous aminophylline. Its use predates the era of 'evidence based medicine' and, as the medication is long out of patent, the resources being put into research of its effects are limited. Nevertheless there is ongoing research into the impact of theophylline in the airways (and the kidneys).

Most of the recent research focuses on the potential role of theophylline to reverse steroid resistance in COPD. A recent review in the Lancet (2009,373;1905-17) by Professor Peter Barnes covers this ground in great detail. A study published in Thorax journal in May (64(5);424-9) randomised a small number of patients (35) to receive either steroids and placebo or steroids and low dose theophylline during an exacerbation. All patients demonstrated evidence of relatively reduced airway inflammation over time - out to 3 months - but there was evidence of a greater reduction in some inflammatory markers (particularly histone deacetylases) in the theophylline group. The study did not evaluate clinically significant parameters.

Incidentally, the European Journal of Clinical Investigation has a forthcoming article (2009 Sep;39(9):793-9) reporting a study in which 217 patients with impaired renal function (GFR 30-60 ml/min) undergoing coronary angiography were randomised to receive either IV saline, IV saline + n-acetyl cysteine or IV saline + NAC + theophylline 200mg twice daily for the day prior and on the day of the angiogram. Contrast induced nephropathy occured in 5, 7 and zero patients in each of the groups respectively.

So, if theophylline protects the kidneys and reduces inflammation in the airways, why are we so slow to use it?

Side effects! Theophylline needs to be kept within a therapeutic range. Caffeine-like side effects occur in many people (nausiea, vomiting, headache, insomnia) at initiation of treatment - and persist in up to 10% . In overdose, side effects can include intractable vomiting, cardiac arrhythmias and seizure. So it's not an entirely safe drug.

Nevertheless, it's a drug with a place - and an old drug that may end up with some real evidence to support our continued use of it after all!

Andrew

OSA and type-2 diabetes - which is the chicken? Or are they both eggs?

A recent round - table expert discussion published in the journal 'Diabetes, Obesity and Metabolism' (11,2009, 733-741) was clearly based on the International Diabetes Federation report on sleep disordered breathing and type 2 diabetes. Each paper attests to a growing interest in the relationship between these two disorders.

Some of the major points were:

1. There is a diabetes epidemic globally. Interstingly the diabetologists are urging the medical community to pay attention to a related epidemic of obstructive sleep apnoea, and to commit to research into how the two may be linked.

2. Obstructive sleep apnoea, some studies have suggested, may contribute to impaired glucose control. And CPAP therapy may reverse the damage. Unfortunately other studies have contradicted this, and the jury is still out.

3. The association between type 2 diabetes and OSA is independent of obesity. Intermittent hypoxia overnight and sleep fragmentation is thought to set off a 'cascade of events' which may contribute to the development of some of the morbidity associated with OSA. Including diabetes. The language is floridly descriptive, but the details are still sketchy!

4. Whether diabetes causes OSA (perhaps via an autonomic neuropathy) or vice versa (chicken or egg), or whether both are simply markers of the same phenotype (both eggs? both chickens? Now that wouldn't be a very productive metaphorical partnership) is open for debate. 40% of patients with OSA have type 2 diabetes, and up to 23% of patients with type 2 diabetes have OSA. So patients in each population group should be evaluated for the possible coexistence of the other condition

5. How to screen patients with diabetes for OSA is not codified. Furthermore, how to evaluate those felt to be at high risk will depend on the local availability of specialist sleep medicine services. The 'expert panel' round table discussion - sponsored by a CPAP company - felt that any patients with a high Epworth Sleepiness Scale or Berlin Questionnaire score should be evaluated with polysomnography. It is worth asking if they snore, or if there have been witnessed apnoeas - as positive answers to these questions significantly heighten the pre-test probability.

6. Treatment of OSA with CPAP may - or may not - help with diabetes control. Weight loss, however, is a clear winner across the board.

Watch this space. If obstructive sleep apnoea hangs on to the coat tails of type 2 diabetes.....

Andrew

Lung cancer news

Lung cancer is a terrible disease, with a significant impact on our community. The attached graph demonstrates mortality rates from lung cancer in Australia over the 94 years to 2004, per 100 000 people. Notice how the peak in deaths from lung cancer amongst men seems to be falling, where amongst women it has risen and -perhaps - plateaued. The late rise amongst women probably represents women taking up the right to smoke in the years around WWII.

In Australian women, lung cancer passed breast cancer as the most common cause of cancer deaths amongst woment - back in 2005. More than 50 Australian women die each week from lung cancer.

If picked up early, there is an 80% chance of being able to cure most lung cancer (Non-small cell lung cancers - NSCLC). However, most lung cancer is not picked up early. If not picked up early, the chance of a cure rapidly falls to below 20%. Generally a cure is only possible if the cancer, and any involved lymph nodes, can be surgically resected.

There has been some noise this week about a new-ish oral chemotherapy agent, Erlotinib (Tarceva). (Erlotinib is an inhibitor of epidermal growth factor (EGFR) tyrosine kinase). Presentations at the 13th World Conference on lung cancer have reported increased disease - free survival if this agent is used immediately following the standard accepted (platinum based) chemotherapy regimens for advanced non-small cell lung cancer. These studies looked at patients who received chemotherapy for NSCLC and did not demonstrate progression of tumour while receiving chemo. This does seem to be progress.

Erlotinib was initially licensed for use in patients who had failed first line chemotherapy (tumours got bigger on chemo) Trials indicated that in this patient group it increased median survival from 4.7 to 6.7 months, and 12 month survival from 21% to 31% of patients. Those numbers don't really float my boat, and are difficult to explain to patients. The recent Saturn trial, however, seems to demonstrate somewhat more impressive results. As always, it's hard to translate chemo / cancer trial results into real life. This trial, however, showed a 41% increase in disease free survival, and a 23% improvement in overall survival (the latter in patients without EGFR mutations - who constitute the bulk of patients with NSCLC but who are considered to respond less well to this sort of EGFR inhibitors). Precisely what these numbers mean in terms of years / months lived and numbers of people surviving is less clear. It is likely, however, that the numbers are more meaningful clinically than the results from the earlier trials, which applied to cancers that progressed on initial chemotherapy.

Erlotinib seems to cause generally tolerable side effects (rash and diarrhoea mainly), and is taken as a tablet once a day. It is likely to be most beneficial in patients with EGFR mutations, and the benefit in those patients has not yet been reported. However, tumours probably become resistant over time. In spite of that misgiving, and the cost - $3300 in Australia per month at present - it is starting to look as if Erlotinib is going to have a continued place in the treatment of advanced non-small cell lung cancer. Hopefully that will be good news for cancer patients.

It certainly seems to be creating a bit of buzz for Roche shareholders.

Andrew

Radiology can be beautiful.

Recently I came across an example of 'mosaic attenuation' on a high resolution CT (HRCT) scan of the chest. There are many rather evocative descriptive terms used in reference to changes seen on this modality of CT scan, and I think that mosaic attenuation is perhaps my favourite.

The attached photo demonstrates this abnormality. Areas of black lung are nestled against areas of 'ground glass' change (think about the smoothed, opaque appearance of a glass fragment found on the beach). These represent areas of differential ventilation and perfusion. On HRCT of the chest, blood is seen as white, air as black and areas where there is a significant amount of both blood flow (perfusion) and air ventilation come up grey. When we have a 'mosaic' there are areas of lung alongside each other which have very different ratios of blood flow to ventilation. Black (more air less blood flow) against grey (more blood flow relatively).

Understanding this, it's apparent that disease process which have an impact on blood circulation in the lungs, or on air flow in tiny airways, in a variable way throughout the lungs may lead to mosaic attenuation. This includes such entities as hypersensitivity pneumonitis (which effects tiny airways, the terminal bronchioles) and pulmonary hypertension. In the attached film, there is evidence of widespread bronchiectasis - which may be the cause of the mosaic attenuation....

But bronchiectasis on CT is another story.