wheeze

The asthma inhaler has become a symbol of our times, ever-more widely prescribed against an ever-spreading ailment. But Liz Hunt, health editor of The Independent, argues that it is a weapon that may carry dangers we have ignored at our peril

What has turned asthma into a killer disease? Before the Sixties, there were around 100,000 cases a year in Britain and a handful of asthma- related deaths. Today, three million people have asthma, and there are 2,000 deaths annually - almost double the number occurring in the Seventies.

As National Asthma Week draws to a close, asthma awareness has never been higher. We are in the grip of a modern-day epidemic and millions of pounds are being committed to discovering why. But are scientists looking in the right place? Environmental issues - ozone levels, thunderstorms, smogs and increasing pollution which are increasingly blamed for the upsurge - have hijacked the research agenda. They are distracting attention from another potential cause of the incidence and severity of the disease - the drugs used to treat asthma, particularly the uniquitous inhalers or "puffer" drugs.

In one small north London primary school, inhalers labelled with the name of the child, occupy four shelves of one cupboard. More than ten per cent of children suffer wheezing, many will grow out of it by the age of ten, but an inhaler is usually prescribed anyway. Everybody knows somebody who carries one. Few will know of the controversy that surrounds their use and rumbles on in the letters columns of the medical journals.

Most asthma specialists don't like to address the matter, dismissing questions raised by curious journalists at the regular press conferences to publicise yet another aspect of asthma. The pharmaceutical industry certainly doesn't, not while there are enormous profits to be made from treating the disease. In 1994, the NHS spent pounds 380 million on prescriptions for asthma drugs - an increase of almost 21 per cent in two years. So hard questions about modern asthma medication go unanswered.

Asthma is a disease of old. Its name means "panting attack" and was first coined by the Greeks. The Ancient Egyptians used crocodile droppings and herb inhalations to treat it, while the Indians of 450ad preferred yoga and acupuncture.

But what distinguishes asthma past from asthma present is that, historically, it wasn't perceived as a potentially fatal disease. As late as 1920, the Oxford Medicine was proclaiming: "Prognosis is excellent. The sensitive type probably never dies in an attack and the non-sensitive type rarely dies in an attack." It wasn't until the Fifties that asthma and fatalities really attracted attention.

The role of asthma drugs, particularly those known as beta-agonists or broncho-dilators, which include such widely prescribed inhaled medicines asVentolin (salbutamol) or Bricanyl (terbutaline), first prompted concern in the Sixties.

These drugs, as their name implies, relax the tiny tubes, the bronchioles, that radiate through the lungs. During an asthma attack, the tubes constrict, producing a frightening shortness of breath, tight chest, and wheezing.

In the mid-Sixties, when asthma deaths began to rise, there was a general perception among asthmatics that the first generation inhalants, such as isoprenaline, were not safe, and their use declined. But as new and reportedly safer beta-agonists hit the market, both doctors and patients grew more confident in their use, and prescriptions for them increased. So, according to a 1986 text book, Recent Advances in Medicine, did the deaths.

As the incidence of asthma and the number of deaths rose steadily during the Eighties, doctors in New Zealand and Canada found themselves struggling to explain a mini-epidemic of asthma fatalities. This was eventually linked to a drug called fenoterol, a beta-agonist which had never been popular in the UK, but which belonged to the same class of drugs as salbutamol and terbutaline. In the Lancet in 1992, scientists from New Zealand posed the question: "Is the cure the cause?"

Other researchers showed that regular use of beta-agonist drugs produced a rebound effect when withdrawn, while over time larger and larger doses were needed to produce the same amount of broncho-dilation. There was evidence that regular use actually produced a deterioration in lung function. The drugs also interfered with magnesium metabolism in the smooth muscle lining the bronchioles, making them even more sensitive.

Then there was studies showing that regular use of beta-agonists could make inhaled steroids, drugs that suppress inflamation and are the first line therapy for asthma, less effective.

In 1990, the first longer-acting beta-agonist, salmeterol, was launched and hailed as a therapeutic breakthrough in asthma treatment. But, according to industry sources, the Committee on Safety of Medicines very nearly failed to grant the drug a licence because one study suggested there were more deaths in a group of severe asthmatics taking it than in the placebo group. This was dismissed as a statistical quirk.

A study by doctors from Nottingham and Canada published in the Lancet in October 1993 showed that salbutamol doubled an individual's sensitivity to allergens such as cat fur and pollen when taken regularly, and that its protective effect eventually wore off. They concluded it posed a serious risk to patients with severe asthma.

A change in the advice given to asthmatics by doctors and pharmacists followed this mounting concern. Regular use of beta-agonists was to be strongly discouraged. The inhalers are now recommended for use "as required", that is, if someone is suffering from shortness of breath or fears an asthma attack is imminent. Preventative therapy relies on steroid inhalers.

Dr Mike Tettenborn, a consultant paediatrician at Eastbourne Hospital NHS Trust, who has a special interest in asthma and environmental concerns, confirms that regular use of beta-agonists is now regarded as harmful. "There is a very clear view that someone who needs a beta-agonist more than four times a week should be looked at again [by his or her doctor]."

However, there is divergence between what doctors and pharmacists tell their patients and what patients on long term therapy for a chronic disease actually do, especially children, and especially with drugs that give immediate relief from an alarming symptoms.

It is children in particular who concern Dr David Freed who has a long history as a dissenting voice in asthma treatment. In 1982, as a senior lecturer in immunology and microbiology at Manchester University where he was a member of the academic staff for 16 years, he was forced from the rostrum by catcalls and jeers from colleagues. He had been invited to address at a meeting at the Wythenshawe Hospital in the city, but he had bad news and they didn't want to hear it. It is we, the doctors, who have turned asthma into a killer, with indiscrimate prescribing, he argued.

Freed now says that by diagnosing these wheezy episodes in children as asthma "we are triggering the doctor's prescribing reflex - furoror therapeuticus - and we might convert a benign transient wheeze into a chronic condition that needs ever-increasing drug intake to keep it under control..."

Dr James Le Fanu, a London GP who writes a weekly newspaper column, has also expressed concern about diagnosis, and has criticised the National Asthma Campaign for "exaggerating the importance and significance" of the illness. "Asthma certainly seems more common but most of the increase can be attributed to a change in diagnostic fashion - many children having asthma would in the past have been diagnosed as suffering from 'wheezy bronchitis'."

Dr Freed has his own theory to explain the transformation of asthma from benign condition to a life-threatening disease. Asthma is essentially an allergic reaction, Dr Freed says, a defence mechanism to alert the body to invading microbes and particles such as pollen and house dust mite droppings - now regarded as the prime cause - and from chemicals, and extremes of heat and cold.

Once initiated, an allergic reaction then triggers an inflammatory process; the blood vessels dilate, protective white blood cells migrate to the area under attack, and in tissues, such as the lungs, there are increased mucous secretion and shedding of cells. This sequence of events aims to trap offending particles and carry them away from the more sensitive membranes.

Dr Freed believes that asthma "must be protective in some way, against some insult. Mother Nature did not put smooth muscle into our bronchi in order to make mischief..." He proposes that the bronchioles constrict during an attack, to allow particles or chemicals which have initiated the allergic reaction to be removed from the lungs. Although the amount of air passing through the bronchioles is reduced, the velocity and turbulence is increased and gives rise to a "scouring" action, removing excess mucus (and any particles trapped in it) away from the inner wall and forcing them up towards the throat.

In Asthma: is your suffering really necessary? by Dr William Fox, published earlier this year, Dr Freed writes: "This effect would be seriously compromised by any drug which permitted the secretion of mucus but prevented it from being carried away... Beta-agonists certainly would be expected to do this." He describes the appearance of the lungs of asthmatics who have died in hospital after an attack preceded by days or weeks of increasingly aggressive treatment. There is a characteristic "widespread plugging" of the bronchioles with thick, hard mucus that has to be cut with a knife.

When, 13 years ago, Dr Freed tried to share his theory with colleagues at Wytheshawe he was appealing to their scientfic judgement. "Instead, what I got was an emotional response," he says. He is philosophical but holds firm to his theory and now runs a private practice as an allergy specialist, using a range of de-sensitisation treatments for asthma and other allergic conditions with some success.

While asthma drugs dominate the prescribing consciousness, there will be little or no investment in alternatives, including pollution reduction, improving household ventilation and better hygiene to reduce the prevalence of the house-mite. "If you swim against the tide in medicine then you make yourself unpopular," Dr Freed says. "Controversy in medicine is not like controversy in any other field. Two physicists can disagree on some aspect of physics and sit down and debate it rationally. In medicine, it is not so easy. What it comes down to is people's lives. Whether or not you are killing patients."