Lung cancer screening

Why are we not screening for lung cancer?

So began an editorial in a recent edition of 'The Blue Journal'. In this particular edition, an Italian group was reporting on the DANTE trial, which investigated - in a randomised and controlled structure - the use of low dose CT scanning (LDCT) as a screening tool for lung cancer.

Now, although - as previously blogged - lung cancer is the leading cause of cancer death in our community, discussions about lung cancer screening don't rate a mention in the mainstream news. (Contrast this with prostate, breast, cervical and bowel cancer for example).

Efforts to determine whether our new, super-duper, multi-camera CT scanners can be utilised to screen for lung cancer have - to date - fallen over at the first hurdle. While they have demonstrated, repeatedly, that if you perform CT scans on lots of middle-aged smokers you identify lots of asymptomatic, early, curable tumours they have not yet proven that taking out these tumours saves lives.

The recent study has struggled at the same point.

What did they do? A total of 2,472 men aged 60 to 75 years, with at least a 20 pkt year smoking history (a packet a day for 20 years equivalent) were randomised to either a baseline LDCT scan and annual LDCT scans over 5 years, or else a baseline chest xray with annual clinical review. The current data cover follow up over a mean of 33 months (ie not a very long time yet).

What did they find? They found 60 patients (4.70%) with lung cancer in the LDCT group (63 cancers in total - some patients had more than one). Twenty-eight cancers were found in the initial scan ( ie over 2% of these people had cancers they didn't know about to begin with ), 25 were found on subsequent scans and ten were found because people developed symptoms between their annual scans. In the control group, they found 36 cancers in 34 patients; 8 at basline, 3 at routine review and the others because patients developed symptoms.

What did they do next? Lots of intervention! Thirty-nine of the 60 patients in the LDCT arm with cancer had resections, and of these 36 were complete resection. In the control group it was 18 of 34 resected, 17 completely. In the LDCT group there were 96 invasive procedures, vs 36 in the control group. As the investigators put it ''we performed three times as many invasive procedures and found twice as many lung cancer cases with LDCT than without it, ...(but) .. the absolute numbers of advanced and lethal lung cancer cases were unfortunately identical in the two arms.....moreover a significant proportion of major surgical procedures (13%) were performed for pulmonary lesions that ultimately turned out to be benign..."

What happened next after all that intervention? Mortality rates in the groups are identical to date. Put in plain English, the same number of people died in each arm of the study.

So, LDCT screening for lung cancer in asymptomatic patients with no history of cancer detects nearly twice as many cancers as a 'chest xray and annual specialist review' approach, leads to a raft of invasive and expensive interventions, and has not been proven to save any lives. Yet.

Andrew

Bronchial Provocation Testing

In recent years bronchial provocation tests have been developed in an attempt to enable clinicians to identify asthma more accurately. These tests have been limited in their use to pulmonary function laboratories because many require specialized equipment or specially trained staff. There are two broad categories of bronchial provocation test, “direct” and “indirect” challenge tests.
Direct challenge tests use pharmacological agents such as histamine or methacholine that act on specific receptors on the bronchial smooth muscle causing it to contract. Indirect challenge tests such as exercise, eucapnic hyperpnea (EVH), adenosine monophosphate (AMP), hypertonic saline or inhaled mannitol (which is what we use in our Lab) work by triggering the release of inflammatory mediators that in turn cause bronchial smooth muscle to contract in sensitive individuals.
We recently enjoyed a visit from Stuart Jack (pictured), the Territory Manager for CareFusion Australia & New Zealand who demonstrated the eucapnic hyperpnea (EVH) kit. EVH is regarded as the “gold standard” challenge to identify exercise-induced asthma particularly in elite athletes. It was developed because clinicians could not be certain that subjects undergoing standard exercise testing were exercising at a sufficiently high intensity to provoke exercise induced asthma. EVH involves the inhalation of dry air with added CO2 (5% CO2 21% O2 74% N2) for 6 minutes at a target ventilation rate based on the subjects FEV1.
Thanks Stuart for a very entertaining and informative visit.
Vanessa

Aspergillus - the prodigal picture

Several weeks ago I blogged about chronic invasive aspergillosis (chronic nectrotising aspergillosis as per the accompanying picture) in COPD / emphysema. The adjacent picture, which has just emerged from the archives of my previous talks and which was borrowed from a forgotten journal article, provides a very helpful schema for remembering how various aspergillus diseases relate to the host (patient) immune response. Thought it was worth posting all by itself.

Andrew

Internet addiction and sleepiness

Tomorrow marks the annual Regional Sleep Medicine day conference, this year being held at Portland District Health. While reading around a case I wish to present I came across some interesting, and sobering, new research on the impact of internet addiction and sleep.

It has been suggested that internet addiction may be an epidemic in the twentyfirst century. A recent study published in the 'Psychiatry and Clinical Neurosciences (2009; 63:455-462) surveyed 2336 high school students in a particular school district in South Korea - that number representing an 87% response rate. Using Young's internet addiction test (everyone should do it just once), 2.5% of boys were found to be internet-addicted, with 53.7% possibly addicted. For girls, the figures were 1.9% and 38.7% respectively.

Excessive daytime sleepiness (EDS) was defined as an Epworth Sleepiness Scale score of more than 10 - which is pretty bad for an adolescent. Using that criterion, and controlling for duration of internet use and sleep time, age, gender, smoking status, painkiller use, symptoms of insomnia, witnessed apnoeas and nightmares the odds ratio for EDS in internet addicts was 5.2(95% CI 2.7 to 10.2) when compared with non-addicts. That means that internet addicts were 5 times more likely to be excessively sleepy in the daytime than non addicts. There was a stepwise increase in prevalence of daytime sleepiness from non-addicts to possible addicts to addicts (7.9%, 13.5% and 28.6% when controlling for the above factors respectively). The attached table shows the increased incidence when controlled for the above associated factors (black) as opposed with the raw initial data.

What has me worried more is that there was a stastically significant increase in prevalence of every sleep problem on the questionnaire, following the same 'J-curve'. This included difficulties with initiation and maintenance of sleep, wakening early in the morning, 'insomnia symptoms', snoring, witnessed apnoeas ( a huge 11% of teen internet addicts), teeth grinding and nightmares.

I think that internet addiction will turn out to be a significant marker for other sleep problems and an independent cause of daytime sleepiness - perhaps by leading to hypervigilance during sleep. Sleep specialists and GPs should consider screening all of our adolescent patients for this - provied we can back this up wth strategies to assist in countering the addiction in those who are 'addicted' and 'possibly addicted'.

Watch this space!

Andrew

The AAPM Conference

The Australian Association of Practice Managers conference was held this month in Melbourne and I attended for one day. As we have a keen interest in being a paperless office the presentation relating to this showed me that we are very well structured and compliant to this stream of office procedure and found that there are several technology advances that we can adapt to improve even more. Life without paper is fantastic.

Our favourite office adaptation this month was the installation of the headsets for our reception staff, so easy to type and talk.

Maureen

Buying a CPAP machine

Part of my role as one of the Practice Nurses here at Regional Respiratory Medicine is to assist people who have been diagnosed as having Obstructive Sleep Apnoea (OSA) to get started on CPAP therapy.

CPAP stands for Continuous Positive Airway Pressure. Basically this is a pump that delivers air (not oxygen) at a fixed pressure through your nose via a mask to keep your upper airway open when sleeping. The idea is that this allows you to then have better quality sleep, which then has the flow on effect of more energy during the day. It does much more than this for your health in the long term, including decreasing your risk of having a heart attack in the future just to name one! But this is not what I want to focus on.

I find that when people are ready to buy their own machine, there is one common question that I get asked rather frequently –

“What sort of machine should I get?”

Well, my advice to people is always the same. I cannot favor or promote any particular CPAP company / machine over over another but generally; you can’t go wrong with the machines on offer out there today as they all will do the same thing. Advances in technology mean that machines of today have been designed for ease of use and comfort, combined with the latest software to record data.

There are a couple of things you might want to consider aside from cost (which is another commonly asked question).

Firstly, consider purchasing a machine that has an inbuilt humidification feature or the option of attaching one at a later date. Until you have tried out a machine it is hard to say for sure if this is a feature that you will or won’t use. However, as we all know, things can and do change - I believe it is better to have this option available.

Secondly, ask about the data which is able to be downloaded from each machine. Some machines provide basic compliance data, while other machines provide more detailed information. Again all information provided is useful to your Consultant during a review. More important than this will be how YOU are finding using your CPAP machine.

At the end of the day, all CPAP machines do the same job and it gets down to personal preference in ease of use, transportability, and cost.

All the best,

Lisa

The 'beta-agonist paradox'

"Clinicians need to be aware of how to identify and manage patients for whom beta-agonist treatment is a problem rather than a solution. They constitute a small but important sub-group of patients with difficult asthma".

As a consequence of recent conversations with hospital staff in Hamilton about our management of a patient with difficult asthma, I thought it would be appropriate to post a blog on this topic. Although beta agonists (such as salbutamol, terbutaline, eformoterol, salbutamol) are essential tools in the management of asthma - either as 'reliever' medications or as part of a 'preventer / maintenance' regime, their role in chronic persistent asthma may not be as simple as we would like to think.

The above quote is from Dr. D.Robin Taylor, at the University of Otago in Dunedin, New Zealand. Dr Taylor was at the coal-face of this issue in New Zealand in the early 1990s, when use of the beta-agonist fenoterol was associated with a spike in asthma related deaths which only ended when that medication was taken off the market. Although the Wikipedia entry on this drug suggests that the surge in deaths was all due to cardiac side effects from patients irresponsibly managing their asthma with massive doses of the medication out of hospital, the issue may not be quite that simple. The 'epidemic' of asthma deaths associated with that medication has helped to generate persistent research into the hypothesis that beta-agonists may paradoxically worsen asthma control in some situations.

I first heard Dr Taylor on this issue as a registrar back in 2002. I was struck by his description of a difficult asthmatic patient who was using bucket-loads of salbutamol as reliever, and who did not improve until - in a carefully managed hospital environment - that beta-agonist was withdrawn. The peak flow record was instructive and convincing.

In a recent issue of the American Journal of Respiratory and Critical Care Medicine (Vol 179, pp976-978) Dr Taylor's summary of evidence and opinion on the question of whether beta-agonists may sometimes be harmful has been published - as a 'clinical commentary'. (The material was initially presented at the 2008 American Thoracic Society conference).

The points I underlined in my copy are as follows:

• the FDA in the USA issued, in 2005, a 'black box' warning about the safety of long acting beta agonists eformoterol and salmeterol. The majority of the relevant committee felt that these medications should only be used in combination with an inhaled corticosteroid (ICS) in treatment of asthma, as the risk of treatment with the beta-agonist alone, without ICS, outweighed the benefit).
• beta-agonists are, if used consistently, pro-inflammatory in human airways (both in-vitro and in-vivo studies). ICS, which are anti-inflammatory, may therefore protect against adverse effects from beta-agonists. To my mind, however, this situation is far from ideal - i.e. that we would need to need to use a medication to treat a medication related side effect.
• although acute use of beta-agonists leads to airway smooth muscle relaxation, in a mouse model chronic beta-agonist stimulation leads to increased airway smooth muscle contractility - and potentially a heightened response to an asthma trigger (i.e. another mechanism - apart from the pro-inflammatory effects - by which the medication may make the disease worse!) "It would appear that acute and chronic B-agonist effects are not the same thing".

So there is evidence that persistent overuse of beta-agonists may cause, within the airways, a process that is difficult/impossible to distinguish from a worsening of the underlying disease process. Now that takes some mulling over!

Two quotes from Dr Taylor's article to summarize:

"...monotherapy with beta-agonists should clearly be avoided, and the use of combination inhalers to some extent guards against the possibility of LABA-related adverse effects. However, the concomitant use of ICS does not mean that adverse effects of beta-agonist are a non-issue: there is likely to be a threshold for adverse effects in relation to total beta-agonist exposure that may be crossed even when patients are taking ...ICS".

"Good asthma management should include appropriate diagnosis and treatment of beta-agonist toxicity......the characteristic features include unstable or intractable asthma with evidence of psychological and/or pharmacological beta-agonist inhaler dependence. The need for frequent "reliever" ... should cause alarm bells to ring, especially if the treatment yields progressively diminishing benefits in a patient with severe asthma (my emphasis)".

Now, I do not want any of my patients to simply stop using their reliever medication. However, we clearly must have a 'zero tolerance' approach to treating asthma with regular beta-agonist alone. Inhaled corticosteroids are essential. If asthma control is difficult then the first priority should be to review the delivery technique for any 'preventer' medication, as even the most competent patients often make a hash of it. But if, in spite of this, more and more salbutamol is required by a patient, with less and less response, then we should ask whether the beta-agonist might be part of the problem - and be ready to do something about that.

Andrew