Airways Disease MDT - 6th May 2014 The inaugural AD-MDT was held on 6/5/14. The AIM of the meeting is to develop the skills and knowledge to be able to run an AD-MDT - the time frame from the start to having a workable meeting should be no more than 3 meetings. Although the main intention is to have a Clinical MDT, it is recognised that this meeting is likely to spawn many aspects of research and consequently the attendees should comprise clinicians from a variety of disciplines as also researchers. The problem was outlined and in essence, although it spans all of airways disease, it is the group of people developing small airways disease that is at the heart of the issue. Although it is obvious when small airways disease has developed by measuring spirometry, this is not a good measure of early disease. There are many people, smokers and neversmokers, asthmatics and non-asthmatics who develop chronic airflow limitation. In the graph below there are about 300 subjects who have airways disease who have never smoked. The younger ones have typical asthma (reversible bronchoconstriction) whereas the older ones tend to have less reversible obstruction and the encircled group, have none at all. Figure 1. +/- 300 never-smoking patients with airways disease on optimal/maximal treatment - each dot is an individual. FEV1% predicted plotted against age 1
Serial spirometry in the younger group looks like this Fig 2: Here there is variable reversible airway narrowing with the FEV remaining associated with the VC. There is no evidence of development of small airways disease. Fig 2: 37 M with serial The older subjects and particularly those encircled in Fig 1, there is no reversibility in the airways obstruction (FEV1 remains stable) despite considerable clinical changes and changes in FVC. Serial spirometry is seen in Fig 3. Here there is small airways obstruction. 5.0 4.0 3.0 2.0 1.0 0.0 01/04/1993 01/09/1993 01/12/1993 FEV FVC 01/05/1994 01/11/1994 01/05/1995 FEV Predicted VC Predicted 01/10/1995 01/04/1996 01/10/1996 01/05/1997 01/07/1997 Fig 3 80 M - never smoked and no history of asthma when younger 01/07/1998 2
The development of irreversible airways disease (or dissociation of FEV and VC, or the development of small airways disease) can be witnessed occasionally over time as in the example in Fig 4. This graph spans nearly 20 years with some irreversibility developing around about 10 years. 5.0 4.0 3.0 2.0 1.0 0.0 FEV FVC FEV Predicted VC Predicted 1 Oct 1982 1 Mar 1983 1 Jun 1986 1 May 1989 1 Aug 1992 1 Nov 1993 1 Mar 1995 1 Oct 1995 1 Feb 1996 1 Jun 1997 1 Feb 1998 1 Nov 1998 1 Oct 2000 1 Oct 2001 It is clear that although Spirometry does in fact reflect the development of irreversible airways obstruction, we need better measurements of Small Airways function if we re going to be able to assess early disease (and perhaps influence its outcome). Developing a core group of investigations for Airways Disease 1. Greg King - newer measurements of Small Airway Function Greg took us through measurements of airways function and in particular Small Airways Measurements of airway function other than spirometry is cumbersome and difficult. MBNW (Multiple Breath Nitrogen Washout) - is a sensitive measurement of airways narrowing but difficult to do other than for research purposes. FOT (Forced Oscillation Technique) measurement - this is a newer technique and is able to measure both large and small airway function. It is less expensive and is nearing the stage at which it can be used clinically. This would give greater insight into the early development of airways disease. Greg went through the science of FOT and its pros and cons. We did not discuss the advantages or otherwise of plotting serial lung function. Lung volumes and DLCO were not really addressed but of course are integral to the assessment of airways disease. 3
2. Sam McCormack - Radiology Imaging in Airways Disease This is not an area that clinical radiology has been helpful. What can we see with HRCT chest: A) ANATOMY Pulmonary lobules: 1-2 cm diameter Septa 100 micron, - visible Centrilobular arteries: 0.2mm, - visible Centrilobular airway (Small airways): <2 mm - not visible - this is because it is only the airway wall that would be imaged and that is too thin. 4
B Consequences of Airway Pathology: CONSTRICTIVE OB EXUDATIVE There is no doubt that we can sometimes see a mosaic pattern in Small Airways Disease and that it represents areas of hyperinflation as is demonstrated above - labeled Constrictive OB. The problem is that treatment invariably doesn t change this pattern and nor does time. The Tree-in-bud (Exudative) pattern shows small areas of centrilobular infiltrates - inflammatory/infective areas in the small airways. C Thoracic VCAR This an advanced imaging software that can look airway wall thickness and follow airway as also divide the lung into segments and calculate/demonstrate amounts of emphysema in each segment. Quite exciting and may be useful but we ll have to wait and see. Measurements of wall thickness derived from airway and lumen diameters with display of inner and outer contours. Automated segmentation of right and left lung and airways. 3D airway tracking with automated measurements of wall thickness for intuitive airway analysis. Lobe segmentation and visualization 5
The image above probably demonstrates the most exciting potential of this software - and with inspiratory and expiratory views may give us some more insight into airways disease. Annabelle Maher - Small Airways Pathology 1. Normal Histology: Large Airway Airways analysis is in its embryonic stages - but the technology is here and we may use it. Respiratory-type epithelium Pseudostratified Ciliated and nonciliated columnar cells Goblet cells Submucosal glands Cartilage : 6
2. Normal Histology: Bronchiole Here is is important to emphasise - NO GOBLET CELLS Cilated columnar epithelial cells Goblet cells Basement membrane Low columnar epithelial cells (ciliated and non-ciliated) No goblet cells 7
3. Normal Histology - parenchyma ALVEOLAR DUCT RESPIRATORY BRONCHIOLE TERMINAL BRONCHIOLE Bronchovascular Bundle 8
ABNORMAL HISTOLOGY 1. Larger Airways - 1. Goblet cell hyperplasia 2. Thickened Basement Membrane Larger airways Goblet cell hyperplasia Normal 2. Small Airways 1. Goblet Cell Metaplasia 2. Mucostasis Small airways Goblet cell metaplasia 9
Small airways Mucostasis In essence we are able to see the pathology of the airways and small airways but we haven t really done this and need to discuss whether getting specimens is possible and whether they can be obtained at bronchoscopy or need more invasive methods. But small airways Goblet Cell metaplasia and Mucostasis would seem to be the major histopathology abnormalities. We have yet to discuss bronchial cytology. The Next Meeting we will present a case for discussion and have presentations on: 1. Airways Normal Flora - Raymond Chan 2. Phenotypes 3. Remodelling 10