Rehabilitating phlegmPhlegm composition and lung diseases. |
Phlegm, the thick greenish-yellow substance we cough up when we have a cold or chest infection, has something of an image problem. But it nevertheless plays an important role in maintaining health.
"Phlegm has a good purpose," explains Dr Jørgen Vestbo at the University of Manchester. "It's made in glands and small cells (called 'goblet cells' – see image above) in the surface of the airways of the lung, and secreted to catch bacteria and particles that we've inhaled, so that we can cough it up again. It's part of the body's defence."
And phlegm might not be the enemy it was believed to be in the 1960s and 1970s, when people thought it was the root cause of chronic lung disease and breathlessness. However, it does appear to play a role in disease, as well as health.
"We've found that if you have lung disease and phlegm on top of the disease, the disease will progress faster," says Dr Vestbo. "Where it would have taken 15–20 years to become disabled without phlegm, it only takes ten years if you have phlegm. You also have a higher risk of dying."
To date, the role of phlegm in what is now known as chronic obstructive pulmonary disease (COPD) – a blanket term for what used to be known as chronic bronchitis and emphysema – remains unclear, despite decades of debate. COPD is a rare example of a chronic disease on the rise. It is thought to cost the UK health service about £1 billion a year and accounts for some 24 million days of lost work every year. Globally, it is the fourth most common cause of death – an estimated 2.7 million in 2001.
Dr Vestbo is attempting to clarify whether patients with COPD produce too much phlegm – or whether the composition of their phlegm is different from that of people without COPD.
"It may be that some phlegm may be different and harmful," hypothesises Dr Vestbo. "Maybe for genetic reasons, people can't make proper phlegm that clears bacteria. The phlegm might be too sticky: although you need some stickiness to catch the bacteria, too much might mean you can't bring it up." He points out that if people have too much mucus they can't clear, the bacteria caught up in the phlegm can flourish and grow in the lungs, leading to chronic infection. Alternatively, he suggests, something in the 'bad' phlegm could be irritating the surface of the lungs, leading to more inflammation.
To find out for sure whether there is such a thing as 'good' and 'bad' phlegm, Dr Vestbo is analysing the mucus of 48 smokers – 24 with COPD and 24 with healthy, normal lung function.
The first step is to look at the composition and properties of phlegm itself, to see if there are differences in the phlegm of smokers with and without COPD.
Next, in collaboration with biochemist Dr Dave Thornton at the University of Manchester, Dr Vestbo plans to examine the composition of the actual mucins (the large molecules that make up mucus), including the polypeptide gene products and the carbohydrates that decorate them. "We want to characterise all the different mucins in the phlegm of each person in the trial," he explains.
Finally, Dr Vestbo also intends to analyse a large group of enzymes – called polypeptide GalNac transferases – that link sugar molecules to the polypeptide chains making up the core of the mucins. The enzymes are present in the goblet cells that line the airway, so will have to be obtained by bronchoscopy – the rather uncomfortable procedure of inserting a tube into patients' airways and removing small tissue samples.
Dr Vestbo believes that these enzymes – and the different pathways they follow to produce different types of mucins – could hold the key to the variation in the characteristics of phlegm between individuals.
The long-term aim is to find out whether phlegm could be a target for intervention. "If you take samples of phlegm, particularly from smokers or people who are exposed to pollution and infections, you could predict who is likely to be susceptible to lung disease," he says. "Then, if you know who's at risk, you can think about measures to reduce their exposure to harmful agents – or perhaps even modify this susceptibility."
Thumbnail image ( homepage): 'Scanning electron micrograph of inner surface of lung, showing alveoli'.
Larger image above: 'Scanning electron micrograph of bronchus showing active hyperplasia (mucus secretion).'
Images from the Medical Photographic Library supplied courtesy of David Gregory and Debbie Marshall.