Researchers are exploring several promising therapeutic avenues for coughs and colds but symptomatic remedies will remain a pharmacy mainstay for some years to come

The sounds of coughing, nose blowing and sneezing are as much a part of winter as Christmas adverts, leaves on the line, and dull, cold, damp weather. 

Coughs are, however, non-specific and can be a side-effect of certain drugs, a consequence of reflux, or a symptom of a serious disease. Now, new guidelines from the European Respiratory Society (ERS) aim to improve the diagnosis and treatment of chronic cough in primary and secondary care.¹ 

Meanwhile, researchers are uncovering the details of the link between rhinovirus, which causes half to two-thirds of common colds,² and asthma exacerbations.³ They even seem to be edging closer to the virological holy grail: a treatment for the common cold.

The ERS guidelines on chronic cough point out that 5-10 per cent of adults will experience “pathologically excessive and protracted cough”. Severe chronic cough can cause complications – such as incontinence, syncope and dysphonia (changes in speech) – that may lead to social isolation, depression and relationship difficulties.¹ 

It is important to be alert for some causes of chronic cough. The guidelines note, for example, that gastro-oesophageal reflux and aspiration can cause many signs and symptoms associated with chronic cough, such as voice and taste changes, and nasal complaints. Aspiration can cause or predispose to bronchitis, bronchiectasis and asthmatic cough.¹ 

Pharmacy teams also need to watch for medicines that can cause chronic cough. 

Angiotensin-converting enzyme (ACE) inhibitors, for example, increase the sensitivity of the cough reflex in most patients.

The ERS guidelines note that about 15 per cent of patients taking ACE inhibitors develop chronic cough, which can emerge at any time during treatment. The guidelines point out that “angiotensin II antagonists do not affect the cough reflex”, while some drugs, including bisphosphonates and calcium channel antagonists, which worsen pre-existing reflux disease, can increase cough.¹ 

The guidelines also note that most adults with chronic cough as their main complaint report an “exquisite sensitivity” to certain inhaled irritants, such as perfumes, bleach and cold air. These irritate the throat and produce an urge to cough. This common clinical presentation suggests a heightened sensitivity of the neuronal pathways that mediate cough underlie the symptoms. 

In addition, the guidelines highlight chronic cough’s “unique epidemiology”: two-thirds of patients are female and prevalence peaks in the 50s and 60s. As a result, ‘cough hypersensitivity syndrome’ is emerging as a distinct diagnosis.¹ 

Asthma and the common cold

Cough is, of course, a common symptom of asthma. Indeed, patients with cough-variant asthma present with cough as their sole symptom. Bronchodilators and anti-inflammatories alleviate cough-variant asthma.¹ With respiratory viral infections the most common asthma trigger, research is now uncovering the details of the link between rhinovirus and asthma exacerbations. 

For instance, between 60 and 80 per cent of children treated in emergency departments for asthma exacerbations have concomitant rhinovirus infections. During one study, researchers exposed people taking inhaled steroids to control their asthma to a strain of rhinovirus. Their asthma worsened, on average, 2.1 days after developing cold symptoms and beta-agonist use rose. 

Lung function did not change after rhinovirus inoculation³ – but lung function only poorly predicts asthma symptoms. One recent study, for example, showed a “weak and statistically insignificant association” between forced expiratory volume in one second as a percentage of predicted and scores on the Asthma Control Questionnaire.⁴ 

Research into the intimate link between rhinovirus and asthma exacerbations helps identify possible treatments

To trigger an exacerbation, the person with asthma also seems to need to encounter an allergen to which they are highly sensitive. In one study, the risk of an exacerbation increased 30-fold in people with asthma who showed raised levels of IgE – the antibodies that defend against parasitic worms and cause atopic disease – to dust mite when they were also exposed to rhinovirus. In addition, people with asthma can be genetically predisposed to developing exacerbations triggered by rhinovirus.³ 

Research into the intimate link between rhinovirus and asthma exacerbations helped identify possible treatments. For instance, targeting IgE and certain cytokines (such as interleukin 13, 25 and 33) seem to reduce the risk of asthma exacerbations triggered by rhinovirus.³ Hopefully, in a few years, we will be able to better treat this perennial problem. In the meantime, it is worth reminding people with asthma to be cautious in the winter.

Common cold cure?

Let us now consider the long-sought treatment for the common cold. Usually, a common cold is a mild, self-limiting nuisance – but rhinovirus can cause more serious ailments including bronchiolitis, otitis media, sinusitis, pneumonia, and exacerbate chronic obstructive pulmonary disease, cystic fibrosis and, as already mentioned, asthma.⁵ 

Developing a vaccine is difficult, partly because of rhinovirus’s diversity. There are at least 160 types of rhinovirus in three species: A, B and C. Most type A and all type B rhinoviruses enter cells by binding to a membrane protein called intercellular adhesion molecule 1 (ICAM-1).5 Other rhinoviruses enter cells using the low-density lipoprotein receptor or a protein called cadherin-related family member 3.⁵ 

Rhinovirus is highly selective: 90 per cent of human rhinovirus serotypes don’t bind to mouse ICAM-1, which means there are few animal models. Moreover, the antigens – the triggers that cause the immune system to mount a protective response – vary widely.² The RNA polymerase is error prone, resulting in a high natural mutation rate, marked genetic diversity and an increased likelihood of drug resistance.⁵ 

To be effective, patients would also need to take the antiviral early in the course of the infection. However, several pathogens cause similar symptoms and there is currently no point-of-care diagnostic test for rhinovirus, although investigations are underway.⁵ 

Despite these difficulties, several studies are assessing possible rhinovirus vaccines.2 Antiviral drugs may be another possibility. In some patients, for example, the combination of ribavirin and PEGylated interferon alpha 2-a, used to treat hepatitis C, seems to increase rhinovirus clearance. 

Many experimental antivirals for rhinovirus seem to bind to the capsid, the virus’s protein outer coat, which blocks binding to ICAM-1 and other targets on the cell. New drugs that interfere with rhinovirus binding, entry and replication therefore seem promising, although it is early days.² Another approach aims to boost the body’s natural antiviral immune responses.⁵ 

While researchers are exploring several promising therapeutic avenues, community pharmacists don’t need to worry about finding alternative winter OTC revenue streams just yet. A vaccine or antiviral drug for rhinovirus is some distance from the clinic for vulnerable people, let alone available to purchase. Symptomatic cold remedies will be a pharmacy mainstay for some years to come.     

Paying lip service to cold sore treatments

For cold sore sufferers, feeling under the weather may lead to an outbreak of the small blisters that develop on the lips or around the mouth. Cold sores are contagious from the moment tingling is first felt to when the cold sore has completely healed.

Cold sores usually clear up by themselves within seven to 10 days, but many sufferers will want to do something to speed the process along. OTC antiviral creams can ease symptoms and speed up healing time, but to be effective they need to be applied as soon as the first signs of a cold sore appear. Other options available include cold sore patches to protect the skin while it heals and electronic devices that treat cold sores with heat therapy, light or lasers.