Bob and Jan

I recently had the pleasure of meeting Bob and Jan. Bob has been using home oxygen now for some time due to a lung condition. At this particular meeting, Bob was using his EverGo Portable Oxygen concentrator which he has had for the last four months.

They are so pleased with it that they were happy to share their story – so read on and thank you BOB and Jan!

Quality of life is a huge issue for people with continuous oxygen requirements. Bob stated that his quality of life has improved simply because he can go out more. He is not reliant on his home oxygen supply anymore. And he now goes out without pushing a big cylinder around everywhere.

The biggest advantage in his view is to not have to constantly keep up his oxygen bottle supply (he needs 5 a day!). This alone made it difficult to travel away for any period of time. I can only imagine the challenge of packing the car with 5 bottles a day, for more than 3 days….space at a premium. What about luggage, grandchildren? It is much easier to pack the concentrator in the car, and of course there is plenty of room for Jan’s shopping now.

Bob and Jan have from the sound of things been taking full advantage of their new found freedom by doing some tripping around in their caravan. They can charge the batteries in the car (12 volt) and as they say – Bobs your Uncle! When he is out he uses it for up to 6 hours a day.

Speaking of Bob, thats him in the photo.

My research also found out that this particular concentrator is light weight, only 4.5 kilograms, has an easy to use touch screen interface ( which I can vouch for), appropriate alarms, Oxygen Percentage Indicator and extra long life batteries. It also comes all neatly packed in a carry bag.

I am aware that this sounds suspiciously like an advertisement for portable oxygen concentrators and I guess in a way it is but WHAT A GREAT AD THEY ARE. I hope that this inspires others or their families to explore this option to improve quality of life.

I wish this lovely couple all the best and many more travels.

Lisa

Teaching lung function to people who already know a bit

The following example of lung function from our lab illustrates an interesting physiological combination of abnormalities.




As anyone who has heard me teach on lung function testing will know, I think there are three steps to interpreting spirometry:

1. Is the forced expiratory ratio (FEV1/FVC) reduced (ie is the spirometry obstructive)? In this case it is not.


2. Is the FVC reduced (ie is there evidence of restriction)? In this case it is.


3. Is there a response to inhaled bronchodilator? A signficant response requires an improvement of 12% and 200ml from baseline in either FEV1 or FVC. In this case there is no such response.

Interpreting the spirometry alone, one could say that this is a restrictive pattern. However, one of the early signs of restriction on spirometry is an elevation of the forced expiratory ratio (FER). In this instance, the FER is tending down (62% at baseline). This raises the possibility that there is underlying obstruction with air trapping, leading to an appearance of restriction on spirometry.

Here is where lung volumes help. Since getting the 'body box' we are now able to do lung volume testing on every new patient. Lung volume measures here confirm that the apparent restriction is marginal - with a total lung capacity / TLC at 85% predicted around the lower limit of normal. Residual volume / RV is plumb average, and the ratio of RV/TLC tending up - suggesting a degree of air trapping.

Is this a true 'mixed defect'? That unusual combination of restriction and obstruction in the one patient? I think it is. Most commonly we see this appearance in older women with COPD and osteoporotic thoracic kyphosis. In this particular case the chest xray appearance is as follows:

Note the perfectly adequately expanded (in fact marginally hyperexpanded) right lung and the elevated hemidiaphragm on the left. This patient has airways disease with signficant obstruction, and in addition restriction due to a paralysed left hemidiaphragm.

A beautiful example!

Andrew

Lung Function Survey

A big thank you to all the medical practitioners that completed the recent survey on our Respiratory Lab. The response rate was a healthy 58%.

The aim of the survey was to rate the service we provided and use this information to implement quality improvement strategies.

The survey focused on rating various components of the service, seeking information on what barriers there are for referring patients and asking for constructive feedback on how we might improve the service.

The results were very encouraging. Seventy one percent of respondents had used the service previously. Of these the overall rating for the service was;

• very high 29%
• high 56%
• low 12%
• very low 1%
• na 2%

Of the 21% who had not referred a patient before the common reasons were lack of information about the service, spirometry on site and distance to travel to testing.

Eighteen comments were provided. A sample of these were;

'referral pad similar to limestone physicians group distributed to gp's'

'more education on GP use of service'

'appointment given at earliest are always good but at the same it I understand wait is bad'.

'

always very prompt and helpful'

'maybe need improved education with ‘others’

'Appt times!!'

'Not in Warrnambool'

'Lack of information about service-best indications for particular test'

'Pt info handouts on expected costs (often raised as a concern in early COPD)'

'make available for patients to see and have tests done locally in Horsham'

These comments highlighted a common thread that more information and education about lung function testing is warranted throughout the region.

During 2010 we intend to visit all practices in the catchment to meet with GP's and practice nurses. We will also continually make sure the medical community is kept up to date with what tests we are offering and dates we will be visiting various locations.

We are also able to offer practical demonstrations of our testing and in early 2010 plan to conduct a demonstration of cardiopulmonary exercise testing at or Hamilton rooms.

Referral forms are available via this link.

Once again thank you to all those who replied. This information is invaluable for the continued growth of this service.

Jessica

Symbicort catching up with Seretide in COPD.

An article published in the blue journal last month, accompanied by an editorial, draws to light two related phenomena. Firstly, the combination of an inhaled corticosteroid, long-acting beta-agonist and tiotropium is beneficial in chronic obstructive pulmonary disease. (This, at long last, gives respiratory physicians the opportunity to use 'triple therapy', a phrase which has an inexplicable allure for medicos). Secondly, for Astra-Zeneca and Symbicort (budesonide/eformoterol) it's all about catching up with Glaxo and Seretide (fluticasone/salmeterol). And they just might do it yet.

The study was a randomised, placebo controlled trial of Spiriva (Tiotropium) alone vs Spiriva and Symbicort (to use the local trade names) in combination. The Symbicort dose was 320/9mcg, which is not a dose marketted in Australia (where we have 100 or 200/6 or 400/12). Around 600 subjects were recruited, 300 or so in each arm. Subjects had to have pretty severe COPD, with an FEV1 of less than 50% predicted on their initial pre-bronchodilator spirometry, although 25% ended up categorised as moderate if the GOLD - compliant definition of post-bronchodilator FEV1 was used.

The goal of the study was to demonstrate improvement in lung function - which they did. There was a 6% improvement in pre-bronchodilator FEV1 at follow up in the 'triple therapy' (TT) group compared with the Spiriva-alone group. There were also more subjects in the TT group with a significantly improved quality of life. Most strikingly, there was a very significant (62%) reduction in exacerbations in the TT group (7.6% of patients vs 18.5% of patients) over the short 12 weeks of the trial. (It's worth noting that the definition of exacerbations here required a hospital attendance, not just an escalation of therapy with glucocorticoids directed by a doctor).

The benefits of this combination of inhaled medications in COPD now seems beyond dispute. There seems to be a class effect (ie Symbicort and Seretide are each beneficial) and we can expect Symbicort to get PBS listing in Australia at some point for patients with moderate COPD, although it does not yet currently have this.

The accompanying editorial in the blue journal does point out the following important points:

1. Although Seretide has not been demonstrated to reduce the frequency of exacerbations, the trials of Seretide in COPD had a more inclusive definition of exacerbation and the drugs can't be compared on this point on the data already to hand;
2. 40% of patients in this trial were already on 'triple therapy' before the trial, and the inhaled steroid and LABA had to be stopped. This may just be an example of trials catching up with clinical practice;
3. Not enough patients of moderate disease severity have been enrolled in the trials. Aparently a recent post-hoc analysis of the TORCH data (one of the Seretide trials) showed that patients categorised as moderate by GOLD criteria (post-bronchodilator FEV1 50-80%) had quite poor prognosis generally in terms of rate of loss of lung function, deterioration of quality of life and rate of exacerbations. If COPD is now being modelled as an inflammatory disorder and patients with relatively early disease do progress why are we not investigating the impact of antiinflammatory inhalers on earlier-stage disease?

So why do I think that Symbicort is working hard to catch up to Seretide, and that the unwritten primary-endpoint here was to win market share in patients with COPD? It strikes me that Astra-Zeneca learnt from the failure of Glaxo to demonstrate a survival-benefit for the Seretide/Spiriva combination in a big trial published in the New England Journal in 2007. Although a lot of useful secondary endpoints were hit in that trial, it is remembered as the trial that missed the jackpot. The current trial has notably not tried to aim so high. It is a short trial, with relatively few patients, and looks to me very much as if is has been put together to demonstrate that Symbicort is also 'good enough' to use in patients with COPD.

The trial authors list the following as goals of treatment in COPD:

• reducing symptoms
• improving health status and exercise tolerance
• reducing the risk of exacerbations.

These management goals are actually limited by the efficacy of the treatments we have available. They were designed for clinicians, not researchers. So having stuck to the established management goals, Astra-Zeneca have now proved that Symbicort helps to do all of what we are already doing better. It strikes me as circular thinking, and a little disappointing. Give me something new to offer my patients! Please.

Notably absent from the list of treatment goals is to 'reduce disease associated mortality'. It's not there as a goal because, apart from smoking cessation and oxygen in select patients, we don't know how to do it yet. Mortality reduction is the most meaningful of all possible treatment goals in established medical research traditions, but I suspect it is beyond the potential of our current medications in COPD.

Andrew

People we meet

Brona Manson (a previously mentioned Irish nurse) has been a practice nurse with the Mildura Aboriginal Health Service for about two and a half years. The service area extends to Robinvale, Swan Hill, Balranald and Dareton (NSW) all who have satellite clinics. Along with her many varied practice nurse duties (every one always seems to need Brona) her main role is supporting indigenous clients with chronic disease including respiratory patients.
Brona carries out “puffer”education with patients and conducts spirometry tests if needed but also utilizes the monthly visiting service offered by Regional Respiratory Medicine. Dr Bradbeer has been consulting at MAHS for the past 18 months along with a respiratory scientist and sometimes practice nurse (which is how I got to meet Brona).
Sleep medicine is a fairly recent service at the clinic. If indicated patients will undergo a home sleep study. Brona or another nurse will visit the patient in their home early in the evening to ‘wire’ them up, and then return to collect the equipment the following day. Downloaded information from the study is then sent to the sleep scientist in Hamilton to be analyzed and reported on. Patients also have access to CPAP (continuous positive airway pressure) machines if required. Brona will fit the patient with a mask, educate them on the use of the machine and offer follow up support as needed. A new area for her too she tells me, so is learning as she goes.
Brona says the biggest challenge to the Health Service is getting clients to attend the clinic even though a pick up and drop off service is provided to assist with access. According to Brona there are many indigenous clients in the community with respiratory or sleep problems who could benefit from the visiting specialist service offered by RRM. A somewhat disjointed referral system and non attendance at appointments means the service is probably not fully utilized. Patients who do attend seem very grateful for the expert care.

Irene Hill

Fit to Dive?

Recently on a trip to Mildura part of the regulator on the DLCO gas bottle was damaged. Thankfully it was still operational on the day. On return Vanessa went to visit some local dive experts to make sure it was fixed correctly.

They were very interested in our Respiratory Lab. In return, the visit generated some interest amongst our staff in what part Respiratory testing plays in Dive Medical Examinations.

Australia apparently has some of the strictest dive guidelines in the world and the Australian Standards 4005.1 need to be adhered to when assessing a diver for a medical examination.

A survey conducted in Queensland a few years ago attempted to assess the variability of opinion regarding fitness to dive among doctors doing dive medical examinations. There was a 64% response rate. Fifteen hypothetical cases were presented. They were asked to classify the cases as either fit to proceed with dive training, unfit to proceed, requiring a referral to specialist and fit after investigation.

Opinion varied greatly. There was a 70% consensus about unfitness in only 4 cases (one of which should have been referred according to AS guidelines) and fitness in only two cases (both should have been referred). For each case that the AS guidelines firmly state as unfit to dive at least one doctor passed as fit.

How does this relate to respiratory disease? Absolute contraindications for diving are Asthma, Lung cysts, obstructive lung disease, lungs that empty unevenly and previous thoracotomy. Relative contraindication are FEV1/FVC ratio of less than 75% and poor physical condition.

Jessica

Biases that make screening programs look good

Too often lung cancers are diagnosed at a late, untreatable stage, as was the cancer in the CT above. An effective lung cancer screening tool would be great!


Last week I described a recent trial that disappointed, failing to prove that lung cancer screening with low-dose CT (LDCT) saves lives. The designers of this trial are to be applauded for their trial design. They have understood, and tried to avoid, three forms of bias which can make a screening program looks like it is working - when it isn't. These biases have had an impact in the field of prostate and breast cancer screening also - where recent evidence suggests that benefits of screening in some populations (for example women aged 40-50) may have been overstated.

Imagine two people with very small, slow growing, early lung cancers attend different hospitals with indigestion, and are seen by different doctors who manage them independently. One doctor, on the barest provocation, arranges a CT chest for his patient and a small tumour is seen. The other patient does not undergo CT chest. After a run of investigations the first patient has his cancer removed and is followed up for 5 years before being declared free of disease. The second patient is discharged home, but 5 years later presents to his doctor coughing up blood - and a large lung cancer is found on chest xray. He too is treated surgically. Two years later, both patients present to their independent doctors with weight loss and abdominal pain. They are found to have distant spread of cancer and both die 6 months later. The first patient, it seems, survived 7.5 years from the time of diagnosis, the second only 2.5 years. Increasing survival from diagnosis for a lung cancer looks like a good thing, but in this instance survival may not really have been increased; both had cancer at time zero, but only one was diagnosed. This lead to an appearance of increased survival when the cancer was just diagnosed earlier. We call this lead time bias.

The second form of bias is like it. Suppose that a screening program only picks up slow-growing tumours. Suppose aggressive tumours generally make their presence felt clinically within about 6 months and are picked up clinically, and therefore not on screening CT. If a trial predominantly picks up slow-growing tumours then it is possible that a trial will seem to indicate increased survival time in patients undergoing screening only because they are the ones with all the slow-growing tumours. this is called 'length bias'.


Finally, lung cancer prevalence increases with age. It is likely that a number of older people die with lung cancer, rather than from it. This was certainly the finding in the recent Dante trial, the subject of the previous blog. A trial of LDCT screening may pick up, and 'cure', a number of indolent tumours that were never going to make their presence felt anyway. This is 'overdiagnosis bias'.

To overcome these biases it is very important that trials of screening programs are run in a randomised and controlled way. There must be a control group managed in 'usual' fashion. The results of a screening program cannot be compared to historical controls/cancer survival data. And they must be run over an adequate number of years to demonstrate if there really is an overall survival benefit. After all, a screening program that doesn't result in less people really dying from lung cancer, while it may serve to employ lots of people in medical jobs, is in essence a waste of time.

Andrew

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