Eosinophils: mischief-makers in asthma

Whatever are eosinophils?

Diagram of eosinophil as seen under the microscope after staining a blood smear with the red dye eosin, which stains the granules in the cytoplasm and with haematoxylin, which stains the nucleus blue. In the body all these things are colourless, of course. The nucleus consists of two lobes. The red-stained granules contain toxic proteins, ready for secretion from the cell. The toxins from the granules are important for killing parasites, but in asthma they are released inappropriately and damage the lining of the air passages. It is one of the objectives of asthma treatment to stop eosinophils from accumulating in your lungs and to stop those already there from causing damage. Steroid inhalers have a key role in doing this.

In normal blood, eosinophils amount to about 0 to 3 percent of the white blood cells, but this is not such a good guide because variation in the number of other cells alters this figure. A figure of 0 percent normally just means that there were no eosinophils among the limited number of white blood cells examined by the technician, and this is quite normal. If the counting is done by machine, eosinophils are normally not counted at all, perhaps giving the false impression that there are none. It is better to express the number of eosinophils in blood as the number in a unit of volume. The normal range is about 0.04 to 0.4 eosinophils x 10^9 per litre in the UK, or 40,000,000 to 400,000,000 per litre, or 40 to 400 per cubic millimetre (microlitre).

The term 'reference range', often used instead of 'normal range', means almost the same as as far as ordinary folk are concerned. For purists and nit-pickers, it avoids making hard-to-justify statements about what is normal, and quite correctly just relates results to the pattern seen in a 'reference population'. Reference ranges will vary from population to population. They may even vary between labs, because of population sampling issues and because no human activity is ever perfectly standardised.

That's all you probably need to know right now. The rest of this page is for those of you who want a bit of a biology lesson about blood cells.

Blood is made of liquid (plasma) and microscopic 'cells'

Most of the cells are red blood cells, (red blood corpuscles), which carry oxygen from our lungs to all parts of the body.

'Corpuscle' is just another word for 'cell'. Literally, it means 'little body'.

White blood cells (white blood corpuscles) are in the blood to defend us against invasion by bacteria, viruses and other particles which get into our bodies which ought not to be there. There are different kinds of white blood cells, each with its own role in our defence. When the body recognises invasion by foreign bacteria, viruses or substances, white blood cells move from the blood to the place where the invasion occurred, and play their role in destroying or expelling the invader or substance. At the same time our bone marrow starts to make far more of the white blood cells than usual, so that their number in the blood increases. The kinds of white blood cell are:

• Neutrophils (polymorphs), which can remove and kill bacteria and particles of foreign material. The name 'neutrophil' ('neutro' = neutral, 'phil' = loving) comes from the fact that they contain granules which are neither acidic nor alkaline. The mixture of dyestuffs used to make cells easily visible under the microscope is concocted to show this, because acidic substances become blue from the dye 'haematoxylin' and alkaline substances become red from the dye 'eosin'. The name 'polymorph' ('poly' = many, 'morph' = shape) comes from the fact that like almost all cells in the body they have a nucleus, but unlike other cells their nucleus can have a variety of (many) shapes, consisting of usually one to five connected lumps or 'lobes'.

• Lymphocytes, ('lympho' = lymph, 'cytes' = cells) are the cells which give our defences the marvellous ability which they have to tell the difference between our own body and things which do not belong there. They get their name from the fact that they are the cells in a body liquid called lymph, which is pumped round the body in delicate little tubes called lymph vessels, rather like whispy versions of blood vessels.

  When we are immunised (either by immunisation or by an infection) it is the lymphocytes which change to react more quickly in future to that infection. But the process is not perfect, and allergic disease is one of the results when our lymphocytes react in a particular way to something which comes from outside the body which does not present any threat in itself.

• Monocytes, ('mono' = single, 'cytes' = cells) have a nucleus of just one blob under the microscope, which is how they get their name, although this isn't too logical, as lymphocytes also have a one-blob nucleus. Their job is a bit similar to that of neutrophils, but they belong to a group of cell types which break up foreign particles and substances for the lymphocytes, which can then handle the recognition of the small fragments.

• Eosinophils, ('eosin' = the name of a red dye, 'phil' = loving) stain red under the microscope because they are full of little packages of poisonous chemicals (toxins) and these show as microscopic granules which stain red. Eosinophils gather wherever there is a parasite infection or an allergic reaction such as allergic asthma, and then release their toxins. The toxins are very efficient at harming parasites, but unfortunately will also harm us if released in the wrong place. So the lining of the lungs becomes damaged in asthma, and one of the most important purposes of asthma treatment is to prevent this damage.

• Basophils, ('baso' = alkali, 'phil' = loving) stain blue under the microscope because they are full of little granules containing histamine which are involved in some allergic reactions. The granules are acidic and combine with the blue alkaline (basic) dye in the mixture of dyes normally used for making blood cells show clearly under the microscope.
  Basophils release the histamine when such an allergic reaction happens. Antihistamines are medicines which prevent histamine from having the effects which make us ill, and they work well in hay fever and most kinds of hives or 'urticaria'. Basophils are very similar to another kind of cell, the mast cell, which does not live in the bloodstream but in the lungs, nose, skin, gut, heart and other organs and is important in allergy. Both kinds of cell release histamine in allergic reactions. Unfortunately they also release quite a lot of other things which are rather similar to histamine in their effects. But antihistamines don't work against these other substances. This means that antihistamines may not make much difference to some allergic illnesses. For example antihistamines help asthma so little that we usually don't use them for asthma. In anaphylactic reactions (anaphylaxis) antihistamines are utterly inadequate on their own if the reaction is at all serious.

• Blood platelets, ('little plates'!) are tiny, much smaller than all the other cells, and are vital for clotting of the blood, protecting us from bleeding dangerously from small injuries.

Frequently asked questions

I've got a 'high eosinophil count'. What does it mean?

Normally there are very few eosinophils in the blood, just a few percent of all the white blood cells. Neutrophils and lymphocytes are far more numerous. The number of eosinophils goes up in allergic diseases such as asthma and atopic eczema, and in some people who have non-allergic asthma. It also goes up in people who have parasite infestations. There are however quite a few other illnesses, a number of which involve the lungs, which can cause eosinophils to increase in numbers. Finding the cause can be a real challenge for doctors unless the cause is common and obvious. Quite often no doctor can find a reason why someone has unusually large numbers of eosinophils in the blood.

Two forms of asthma cause particularly high eosinophil counts in the blood. Both are rare, unlike ordinary forms of asthma, which are very common. It is important not to jump to the conclusion that you have an illness just because you have read about it, something we are all rather prone to do sometimes. Should you think any of these conditions are a possibility, get an opinion from your own doctor, who is trained to take a sensible approach for you. It is all too easy to suffer needlessly from fear of illnesses you don't have if you are not guided by your own doctor.

The first of these forms of asthma is bronchopulmonary aspergillosis, a serious allergy to a common fungus which can grow inside the lungs. We can recognise this by skin and blood tests: most doctors rely on the blood test for 'Aspergillus precipitins'. An X-ray of the lungs shows shadows which may change a lot with time, and we don't see such shadows in ordinary asthma. Special cross-sectional x-rays (CAT scans) may show other changes which don't happen in ordinary asthma. Bronchopulmonary aspergillosis needs quite a different approach to treatment, from a respiratory physician specialist. This is because it can damage the lungs in a different and more severe way than plain asthma, and because the right treatment will prevent this to a large extent. So it is important to diagnose it as early as possible, and doctors will test many patients with asthma just in case this is the diagnosis. Don't get worried just because you are having such tests; it is your doctor's job to be vigilant and consider all sorts of diseases if there is even a small possibility you might have them. On the other hand, bronchopulmonary aspergillosis looks just like ordinary asthma in the early stages, though an unusually high eosinophil count in the blood compared to most asthma should make us suspicious. Unavoidably, people with bronchopulmonary aspergillosis will have a diagnosis of ordinary asthma in the early stages.

The second rare form of asthma with particularly high eosinophil counts is 'Churg-Strauss syndrome'. This also usually starts out looking exactly like ordinary asthma, and there may be a long period during which even the best asthma specialist will not suspect or be sure of the diagnosis. What usually gives the game away is that unmistakeable numbness or weakness of some part of the body shows that there is more to it. It is damage to the nerves which causes numbness or weakness and Churg-Strauss syndrome can affect quite a number of parts of the body other than the lungs seriously in yet other ways. This rare serious illness needs prompt treatment from a specialist centre, usually using steroid tablets and special 'immunosuppressive' drugs. Most patients do very well on these treatments, but will need careful health checks for many years afterwards.

A very few people who have taken asthma treatment tablets called 'leukotriene receptor antagonists' have turned out to have Churg-Strauss syndrome. The 'leukotriene receptor antagonists' are montelukast (Singulair) and zafirlukast (Accolate). At the moment (May 2001) it looks as if this happened because these people really had unrecognised Churg-Strauss syndrome in the first place and the drugs were not to blame. Since it is quite a long time since the suspicion was raised, it now seems most unlikely to me that there is a problem here which need deter you from taking these medicines. My own practice is to prescribe these drugs when I think someone might benefit substantially from them, and stop the prescription if they don't. I tell them of the concern and keep a list of their names in case we need to contact them should this become necessary. Most family doctors now automatically keep a computer record of treatments prescribed for each patient. In the UK, frustratingly, hospitals are an exception.

Amongst yet other illnesses with a high number of eosinophils in the blood is 'tropical eosinophilia', an illness involving the lungs and caused by parasites called Microfilaria in people who have lived in tropical countries. Treatment is with an anti-parasite drug. Some reactions to drug treatments can cause high eosinophil counts in the blood. Most of these other illnesses do not really cause asthma symptoms, though some do. It's a complicated area, and you need the help of your own doctor if this is a possibility. It could even be that your eosinophil count has no special significance apart from the fact that you have something like asthma or an allergy.

My eosinophil count is zero. Does this mean I am ill?

Not at all. In healthy people there are so few eosinophils in the blood that it can happen that the person counting the cells under a microscope does not find any. Nowadays we mostly use machines for this work, and the machines normally cannot count eosinophils at all. So the printed blood report seems to say there are none, but this is meaningless.

I do not know whether there is such a thing as a medical condition in which eosinophils are truly absent. I am certainly not aware of anyone being ill as a result.

In fact a low or zero eosinophil count, if it has been done by a human being instead of a machine, is a good sign. It argues against severe forms of diseases which raise the eosinophil count, including the kind of allergy which can raise the count. Far from being a sign of illness, it could be a sign of good health.

Remember, information looked up on the internet is not a substitute for the opinion of your doctor.