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Snots' corner - cold remedies

The season of mists and mellow fruitfulness is upon us, bringing with it the runny nose, sneezes and other symptoms of the common cold. Bandolier has its own remedy (trade secret), so was impressed to see two large randomised controlled trials of things that, while they do not promise an end to suffering from the common cold, show that good research is going on to help with the paracetamol, hot lemon, whisky and bed.

Reading the papers was enlightening. According to references in them, the average US adult has two to four colds a year, while children have an average of six to eight a year. The mean duration is seven days (but with a standard deviation of 6 days, so that some can last three weeks).

Nasal spray for runny noses



One study examined intranasal ipratropium bromide (84 µg/nostril, up to four times a day) versus placebo vehicle or no treatment in 411 patients (137 per group) with common cold for no more than 36 hours [1]. Patients had to have moderately severe rhinorrhoea, defined by visual analogue scale and by collection of at least 1.5 g of nasal discharge over a one hour baseline period. Randomisation and its concealment were well done, and the assessments were double blind except for the no-treatment group.

Outcomes - silver sleeves



Outcomes were collection of nasal discharge for up to six hours on days 1 and 2, visual analogue scales, and categorical assessments on days 1 and 2, with a global assessment on day 5.

Results



Because common colds are self-limited, amounts of nasal discharge collected and self-reporting of symptoms improved on days 1 and 2 in all groups. The improvements were greatest in patients treated with ipratropium and least in the no-treatment controls. Patients given the control vehicle (mostly saline) had intermediate improvements.

NNTs could be derived from patient scores on days 1 and 2, and globally on day 5. How good ipratropium bromide looked depended on whether the comparison was with the vehicle control or no treatment. Best estimates were against no treatment, suggesting that intranasal saline itself was having an effect. The best interpretation was from the global (5 day) comparison with no treatment, which produced an NNT of 1.6 (1.4 - 1.9).

Effectiveness and adverse effects of intranasal ipratropium in common colds
Outcome
NNT against vehicle
NNT against no treatment
Patient assessment of effectiveness on day 1 (better or much better)
7.1 (4.3 - 22)
3.3 (2.5 - 5.0)
Patient assessment of effectiveness on day 2 (better or much better)
7.1 (4.0 - 34)
5.6 (3.5 - 15)
Patient global assessment of effectiveness on day 5 (better or much better)
6.3 (3.8 - 17)
1.6 (1.4 - 1.9)
Blood-tinged mucus
7.7 (5 - 16)
6.7 (5 - 13)
Nasal dryness
12 (7 - 56)
8.3 (6 - 16)
Headache
14 (8 - 46)
13 (8 - 32)


Adverse effects were also noted, among them blood-tinged mucus, nasal dryness and headache producing significantly increased incidences. Nose bleed was a rare problem.

Zinc lozenges to cure the cold

There are several biologically plausible reasons why zinc may help in ameliorating symptoms of the common cold. One is that zinc apparently combines with the negatively charged carboxyl termini of the rhinovirus coat to prevent it entering cells. This stops the virus reproducing further.

This second paper [2] was a delight to read for several reasons. Firstly the authors state up front that they determined that a 50% reduction in the duration of symptoms was what they considered a significant clinical effect. What follows can be judged by that. More interesting was that they encouraged recruitment by entering patients who completed the study into a raffle for one of two prizes: dinner for two or a trip for two to the Bahamas! Even better was to see the restaurant in Cleveland acknowledged at the end of the paper.

It was a randomised study of 100 patients given identical lozenges which contained 13.3 mg zinc (as the gluconate trihydrate). Patients with cold symptoms (a median of eight out of ten symptoms) for 24 hours or less were given a pack of lozenges and told to suck one every two hours while awake.

Outcomes

Symptoms were scored daily by using diaries. The main outcome was complete resolution of the cold symptoms.

Results

The median time to resolution of all symptoms was 4.4 days for the zinc treated group, compared with 7.6 days for those treated with placebo. The NNTs for complete resolution with zinc compared with placebo at various times is shown in the Table.
Effects of zinc lozenges on resolution of common cold symptoms
Day of treatment Cold completely resolved with zinc lozenge Cold completely resolved with placebo lozenge NNT (95% CI)
3 16/50 7/50 5.6 (2.9 - 53)
6 34/50 19/50 3.3 (2.1 - 8.8)
9 47/50 30/50 2.9 (2.0 - 5.3)
12 49/50 35/50 3.6 (2.4 - 6.8)
15 50/50 41/50 5.6 (3.5 - 14)

Between days 6 and 12, the NNT was about 3, meaning that for every three patients treated with zinc lozenges, one had cold symptoms resolved who would not have had they been given placebo.

There were some adverse effects. Patients given the zinc lozenges reported bad taste and nausea more frequently.

Comment

The common cold has no definite or simple cure, and over-the-counter medicines will be the first line treatment for almost all sufferers. Both these trials were pharmaceutical company sponsored, at least in part. Knowing that nasal sprays will benefit some patients with excessively running noses may help in some cases. Zinc gluconate is not in the British Pharmacopoeia, so far as Bandolier can ascertain at the time of going to press, though it may be a health shop product.

Zinc gluconate would appear to be a useful addition to the bathroom cabinet, but can anyone tell us where to get it? Alternatively, where can we enrol in a study which at least gives us a chance for a trip to the Bahamas?

References:

  1. FG Hayden, L Diamond, PB Wood, DC Korts, MT Wecker. Effectiveness and safety of intranasal ipratropium bromide in common colds. Annals of Internal Medicine 1996 125: 89-97.
  2. SB Mossad, ML Mackin, SV Medendorp, P Mason. Zinc gluconate lozenges for treating the common cold. Annals of Internal Medicine 1996 125: 81-88.



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