A number of factors conspired yesterday to create our best and most productive day in Mildura to date.

Ms Mills was happy with the ride. Which was just as well, as she was bringing the mobile lung function lab with her. Our gas cylinder was too big for the plane, so had been sent on ahead, by road.

The bigger plane halved the duration of the flight by comparison with the last trip. That, and the longer daylight hours (although the Chief told us he could fly this plane with his eyes closed in the dark) meant we could fit in a full working day in Mildura.

Which was just as well. Ms Mills had the lung function lab operational in no time (she really is very good at her job). The cylinder had arrived, with attached regulator only slightly mangled but useable. After a trio of quick tests the gear was hurriedly, but in expert fashion, dismantled and we hastened to present at lunch-time meeting of the Tristar - 'nice place you've got here. Sure it's big enough?' - Medical Group clinical staff. Sadly this meant that our lunch venue was predetermined and not up to its usual standard.

Every patient turned up, thanks to the efforts of the local Irish nurse. We saw some patients from outside the aboriginal health service. The tests all worked and were all useful. The local Tristar GPs were very interested that we have helped the aboriginal health service establish a home sleep study service, which the health service is happy to open up to outside referrals. I am looking forward to continuing to offer the lung function testing service from the same base.

All-in-all it was a very satisfactory day, capped off by a picturesque flight home over a wet agrarian landscape.

Andrew

Invasive aspergillosis in COPD

Patients with COPD can, as previously blogged, suffer a range of illnesses caused by the ubiquitous fungus, Aspergillus fumigatus. Of all of these, chronic invasive aspergillosis is the entity I have seen least. Until the last few days.

When I first began to get a handle on aspergillus disease, I thought that invasive aspergillosis was the domain of bone-marrow transplant recipients. It turns out that patients with COPD (particularly emphysema) develop a more indolent form of the disease which looks radiologically pretty similar. However, the prevalence of this condition amongst patients with COPD is unknown. Mortality rates are quoted as between 72 and 95%. And they are not falling, in contrast with mortality rates amongst bone-marrow transplant recipients with invasive aspergillosis..

We should consider this diagnosis in all patients with COPD who have progressive lung infiltrates, or pneumonia which fails to resolve as it should after standard antibiotics.

I have just read a helpful review article in a COPD journal on this topic, and have been reminded that aspergillus spores are tiny - about 2-3microns. When inhaled they end up in the furthest reaches of the respiratory tree - the alveoli. There they can germinate into hyphae which - unless they are mopped up by polymorphonuclear cells - can become invasive.

People with COPD are prone to invasive aspergillosis becuause:
- they are often malnourished;
- they have impaired airway ciliary function;
- consumption of broad spectrum antibiotics may have altered the airway microflora to benefit the fungus;
- aspergillus may be able to grow in a biofilm in these patients, like pseudomonas and haemophilus;
- use of corticosteroids has impaired neutrophil function and altered the distribution of neutrophils.

Diagnosis of invasive aspergillosis can be regarded as either proven, probable or possible. To prove the diagnosis requires demonstration of hyphae in tissue - ie a biopsy, which might carry with it considerable morbidity in these patients. A probable diagnosis can be based on a coalescence of appropriate host, clinical and mycological factors (eg the patient is in an at risk group with the right presentation, the CT scan looks right and the fungus is there - in repeated culture or in a bronchoscopy specimen). It is reasonable to embark on treatment based on a probable - rather than proven - diagnosis (sounding very similar here to the 'clinical conference consensus' vs 'pathology gold standard' diagnostic conversation in fibrosing lung disease).

Voriconazole should probably be the first line treatment of this condition. In Australia, however, Voriconazole is available on the PBS only for patients with invasive aspergillosis who have not tolerated Amphotericin B. These criteria were not drawn up for the COPD patients with this diagnosis who are generally ambulatory, slowly losing weight, progressively breathless but at home. Rather they were established with the sick bone-marrow transplant patient in mind. It makes far more sense to initiate the ambulatory COPD patients on oral Voriconazole than to admit them to hospital for a protracted course of amphotericin B. We are, however, going to have to do a lot more research with these patients even to demonstrate that they are a significant population before that realisation trickles through to the PBS.

Andrew

COPD and stiff arteries

COPD is increasingly prevalent, and an increasingly common cause of death. It is currently the fourth leading cause of death in the USA. Patients with COPD often die of other diseases, such as cardiac disease - which is currently the leading cause of death in that country and ours. In the last 10 years there has been increasing recognition that COPD is a disease with systemic effects, beyond the lungs. Death from ischaemic heart disease has been associated with lowered FEV1 (a fivefold in death from AMI as FEV1 fell from 109 to 88% of predicted in a US population). However, establishing how COPD may be a discrete risk factor in cardiovascular disease, distinct from the common risk factor of cigarette smoking, is proving difficult.

A paper in the September 15th edition of the AJRCCM (180 pp513-520) has shed some light on this subject, and scored an accompanying editorial. In this study 18 men with COPD were matched (smoking history and age) with 17 controls who did not have COPD. Pulse wave velocity and pulse wave analysis at carotid, radial and femoral arteries indicate significantly increased arterial stiffness in the subjects with COPD. A complicated array of tests of endothelial function did not indicate any difference between the groups.

Central arterial stiffness is, according to the article and the editorial, a predictor of cardiovascular mortality. It is usually due to either smooth muscle or endothelial dysfunction or elastin loss - or a combination of all three. Given the equivalent endothelial function between the groups in this study, the authors surmised that COPD may lead to elastin degradation in arterial walls. This may be a means by which COPD leads to increased cardiovascular risk independent of other risk factors.

Other studies have suggested that there is endothelial dysfunction in COPD, and that it is worse in patients with lower FEV1 or more extensive emphysema - evidence which is not in agreement with that presented in the recent study. Obviously more work - much more work -needs to be done (I hate hearing that line at conferences, but there it is!)

Anyway, the most tantalising part of the picture is the question of clinical relevance. All of this cardiovascular science is news to me, but it turns out that simvastatin has been shown to reduce arterial stiffness in patients with rheumatoid arthritis. There is also some evidence that statins reduce lung parenchymal destruction and pulmonary vascular remodelling in smoking-related lung disease. So although this is far from being evidence based medicine, we might have some reason to anticipate statins becoming part of routine respiratory medicine in the future.

Andrew

Australasian Sleep Association conference

I've just enjoyed a day at the Sofitel on Collins - not a bad location for the Australasian Sleep Association conference. A good opportunity to catch up with the latest directions in research, as well as to reconnect with colleagues from around the country. I'm tweeting my responses to the presentations as I go - so if anyone is interested, feel free to check out my take on the ASA conference this year @DrBradbeer on Twitter.
Andrew

Lab news

With the advent of day light saving and spring in the air I was looking forward to a walk up to the Frances Hewett Community Health Centre where I had been invited to speak at the monthly meeting of the Respiratory Support Group.
Alas in the freezing cold and blistering rain I drove the short distance not expecting a large turnout. To my surprise a dedicated group had braved the conditions to enjoy the support of a group of individuals including their families and carers who suffer from a lung condition.
My objectives with my power point presentation were to review basic pulmonary anatomy and physiology, give an understanding of the reasons lung function tests are performed, describe the technique and basic interpretation of spirometry and know how lung function tests are clinically applied.
A number of the group had undergone a lung function test at some stage in their lives including the visiting nursing student from Latrobe who during her training had undergone a lung function test and all commented on the effort required to perform an acceptable test.
The presentation provoked some lively discussion. The most interesting and challenging question of the session was ‘how long do you think you would have to train to be a freediver in a competitive apnea sport?’ I am hoping this is not a reflection of how those in the group have felt whilst undergoing a lung function test in our lab?
To quote a comment in the latest ANZSRS newsletter ‘letting the mind wander like this is healthy as long as the piece of string remains attached so that it can find its way back’
Vanessa

Practice Nurses

This week an additional practice nurse began working at RRM. This will enable full time nurse support. The role of the practice nurse has evolved over the past eighteen months to the point where its difficult to imagine how we ever managed without one! Having full time nurse support increases the quality of care for patients and provides essential support in patient education for respiratory and sleep conditions.

One of our consulting rooms now is totally dedicated to the nurses. The practice continues to grow and there is a need to employ new staff which is fantastic, only one issue where are we going to put everybody!

Jessica

High resolution CT scanning and IPF

With the recent arrival of a new CT scanner in Hamilton, I've been reading an article in this month's Respirology journal by a group from the University of Michigan. This review recaps evidence and their clinical practice when it comes to diagnosis of idiopathic pulmonary fibrosis.

An editorial in the same journal reiterates that there are, as yet, no proven treatments for this condition - although colleagues at the Royal Melbourne Hospital and The Alfred Hospital in Melbourne are currently participating in a trial of two novel endothelin receptor antagonists (like Bosentan, currently used to trat pulmonary hypertension) in IPF. (These trials are currently enrolling patients with IPF, with minimal honeycomb change and with a forced vital capacity on spirometry of over 50% predicted).

Idiopathic pulmonary fibrosis is a diagnosis now often made without lung biopsy. A multidisciplinary evaluation must exclude known causes of pulmonary fibrosis which can result in the same radiological appearance - such as pulmonary fibrosis associated with connective tissue disease (eg rheumatoid arthritis or scleroderma); chronic hypersensitivity pneumonitis; or asbestosis - and must include a high resolution CT scan of the chest. If the CT appearance is agreed to demonstrate features of usual interstitial pneumonia - which is the pathological/radiological appearance in idiopathic pulmonary fibrosis - in the absence of an underlying cause then IPF is diagnosed.

As simple as that! The major centres / city hospitals tell us, however, that there is a lot of operator variability outside of the major centres. Which means that it is important for people with this condition to be evaluated in an environment where people really know their stuff. Or perhaps, according to the major centres, all patients with IPF should be evaluated in the major centres.

The following table was offered as, in my opinion, a quite useful summary of the important radiological features of usual interstitial pneumonia:

Definite usual interstitial pneumonia

• subpleural basal distribution
• predominant honeycomb
• interlobular septal thickening
• traction bronchiectasis
• no predominant ground glass attenuation

Consistent with usual interstitial pneumonia

• subpleural, basal distribution
• minimal or equivocal honeycomb
• interlobular septal thickening
• traction bronchiectasis
• no predominant ground glass attenuation

Suggestive of alternate diagnosis

• No honeycomb, with one or more of the following as the predominant HRCT finding;
• upper or mid lung distribution
• peribronchovascular distribution
• ground glass attenuation
• micronodules
• discrete cysts
• air trapping
• consolidation

This seems to be the poster they hang on the wall of the registrars' reporting room at Ann Arbor. I'll have to run it past my local radiology colleagues and see what they think - but it looks pretty good to me.

Supports for patients with a diagnosis of pulmonary fibrosis are lacking in the Australian community. The Pulmonary Fibrosis Foundation in the USA runs a pretty informative website and supports good research. I am not aware of a comparable group in Australia.

Andrew