E. 感冒に対する解熱剤の影響

・ロキソニンで風邪が早く治るわけではない

・しかし、辛い症状は軽減してくれる

ということです。

（※　管理者注）

**********************************************

37の比較を説明し、1069人の参加者の9つのRCTを含めました。

含まれた研究におけるバイアスの全体的なリスクはまちまちでした。

分析では、NSAIDは総症状スコア（SMD -0.40、95％CI -1.03〜0.24、3つの研究、変量効果モデル）、または風邪の持続時間（MD -0.23、95％CI -1.75〜1.29、変量効果モデルの2つの研究）を有意に減少させませんでした。

呼吸器症状では、咳は改善しませんでしたが（SMD ‐0.05、95％CI ‐0.66から0.56、2つの研究、変量効果モデル）、くしゃみスコアは大幅に改善しました（SMD ‐0.44、95％CI ‐0.75から‐0.12、2研究、変量効果モデル）。

NSAIDの鎮痛効果（頭痛、耳の痛み、筋肉と関節の痛み）に関連する転帰については、この治療は大きな利益をもたらしました。

副作用のリスクはNSAIDでは高くなく（RR 2.94、95％CI 0.51〜17.03、2つの研究、変量効果モデル）、そのような薬物がプラセボと変わらないと結論することは困難です。

Cochrane Database of Systematic Reviews

Non‐steroidal anti‐inflammatory drugs for the common cold

Cochrane Systematic Review - Intervention Version published: 04 June 2013 see what's new

https://doi.org/10.1002/14651858.CD006362.pub3

Soo Young Kim, Yoon‐Jung Chang, Hye Min Cho, Ye‐Won Hwang, Yoo Sun Moon

https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006362.pub3/full/ja

Abstract

Background

Non‐steroidal anti‐inflammatory drugs (NSAIDs) have been widely used for the treatment of pain and fever associated with the common cold. However, there is no systematic review to assess the effects of NSAIDs in treating the common cold.

Objectives

To determine the effects of NSAIDs versus placebo (and other treatments) on signs and symptoms of the common cold, and to determine any adverse effects of NSAIDs in people with the common cold.

Search methods

We searched CENTRAL (The Cochrane Library 2013, Issue 1), MEDLINE (January 1966 to April week 4, 2013), EMBASE (January 1980 to April 2013), CINAHL (January 1982 to April 2013) and ProQuest Digital Dissertations (January 1938 to April 2013).

Selection criteria

Randomised controlled trials (RCTs) of NSAIDS in adults or children with the common cold.

Data collection and analysis

Four review authors extracted data. We subdivided trials into placebo‐controlled RCTs and head‐to‐head comparisons of NSAIDs. We extracted and summarised data on global efficacies of analgesic effects (such as reduction of headache and myalgia), non‐analgesic effects (such as reduction of nasal symptoms, cough, sputum and sneezing) and side effects. We expressed dichotomous outcomes as risk ratios (RR) with 95% confidence intervals (CI) and continuous data as mean differences (MD) or standardised mean differences (SMD). We pooled data using the fixed‐ and random‐effects models.

Main results

We included nine RCTs with 1069 participants, describing 37 comparisons: six were NSAIDs versus placebo and three were NSAIDs versus NSAIDs. The overall risk of bias in the included studies was mixed. In a pooled analysis, NSAIDs did not significantly reduce the total symptom score (SMD ‐0.40, 95% CI ‐1.03 to 0.24, three studies, random‐effects model), or duration of colds (MD ‐0.23, 95% CI ‐1.75 to 1.29, two studies, random‐effects model). For respiratory symptoms, cough did not improve (SMD ‐0.05, 95% CI ‐0.66 to 0.56, two studies, random‐effects model) but the sneezing score significantly improved (SMD ‐0.44, 95% CI ‐0.75 to ‐0.12, two studies, random‐effects model). For outcomes related to the analgesic effects of NSAIDs (headache, ear pain, and muscle and joint pain) the treatment produced significant benefits. The risk of adverse effects was not high with NSAIDs (RR 2.94, 95% CI 0.51 to 17.03, two studies, random‐effects model) and it is difficult to conclude that such drugs are not different from placebo.

Authors' conclusions

NSAIDs are somewhat effective in relieving discomfort caused by a cold but there is no clear evidence of their effect in easing respiratory symptoms. The balance of benefit and harms needs to be considered when using NSAIDs for colds.

Plain language summary

Non‐steroidal anti‐inflammatory drugs for the common cold

The common cold is the most common and widespread illness known to humans. Non‐steroidal anti‐inflammatory drugs (NSAIDs) for example, aspirin, ibuprofen and naproxen, have analgesic (pain reducing), antipyretic (fever reducing) and, in higher doses, anti‐inflammatory effects. NSAIDs have been widely used for over a century for the treatment of pain and fever associated with the common cold and so it important to assess the efficacy of using NSAIDs for treating pain or fever associated with the common cold.

This review found nine studies (including 1069 participants) that compared various NSAIDs either with each other or with an inactive substance that has no treatment value (placebo). Our findings suggest that NSAIDs may improve most analgesia‐related symptoms caused by the common cold, but there is no clear evidence that NSAIDs are effective in improving coughs and runny noses caused by the common cold.

Some of the included trials reported gastrointestinal complaints, rash and oedema in the NSAIDs group. Major limitations of this review were that the results of the studies are quite diverse and the number of studies for one result is quite small. For this reason, it is difficult to draw any strong conclusions.

Authors' conclusions

Implications for practice

Non‐steroidal anti‐inflammatory drugs (NSAIDs) are somewhat effective in relieving discomfort caused by a cold but there is no clear evidence of their effect in easing respiratory symptoms. The balance of benefit and harms needs to be considered when using NSAIDs for colds.

Implications for research

We were unable to support the theory that NSAIDs are effective in reducing cough based upon the data included in this review. A large trial to study the effect of NSAIDs on colds may make this relationship clearer. For analgesic effects on the common cold, acetaminophen is also frequently used along with NSAIDs. However, in this review, we did not examine which of these treatments was superior in terms of effect or safety. For this evaluation, we consider another review necessary.

Background

Description of the condition

The common cold is an acute respiratory tract infection (ARTI) and is the most common and widespread illness known to humans, affecting all age groups. Young children suffer an average of six to eight colds a year, while adults experience approximately two to four colds a year. Although the common cold is usually mild, with symptoms lasting one to two weeks, it is a leading cause of medical visits and days missed from school and work (Heikkinen 2003). Nasal congestion, rhinorrhoea, sneezing and coughing accompanied by general malaise are typical symptoms of the common cold. Over 200 serologically different viral types are responsible for common colds, with the rhinovirus being the most common cause (Eccles 2005).

Description of the intervention

Despite ongoing research into antiviral drugs, there are no effective therapies for the prevention or treatment of the common cold. Therefore, treatment of colds is normally aimed at relieving the symptoms of the illness. Several classes of drugs are currently available, including decongestants, anticholinergics, antihistamines and antitussives. These are effective, to a greater or lesser extent, in treating symptoms of the common cold (AlBalawi 2011; De Sutter 2012; Li 2010; Ostberg 1997; Saraswat 2011; Smith 2012).

How the intervention might work

NSAIDs have been widely used for over a century for the treatment of pain and fever associated with the common cold. Despite their widespread present day use and the long medical history of the use of NSAIDs in relieving pain associated with the common cold, there is a lack of clinical data to support the efficacy of NSAIDs treating this condition. There is some evidence that cold symptoms might be the result of inflammatory mediators such as kinins and prostaglandins, which can be blocked by NSAIDs, rather than the result of the direct cytopathic effects of viruses (Eccles 2005; Gwaltney 2002).

Why it is important to do this review

Several studies have proposed that NSAIDs could be effective in alleviating common cold symptoms, including sneezing and coughing (Sperber 1989; Sperber 1992; Winther 2001). However, no consensus has been reached on this issue. This systematic review is an update of a Cochrane review first published in 2009 (Kim 2009).

Objectives

To determine the effects of NSAIDs versus placebo (and other treatments) on signs and symptoms of the common cold, and to determine any adverse effects of NSAIDs in people with the common cold.

Results

Description of studies

In the vast majority of studies, the clinical symptoms of the common cold, requirements for inclusion, type and dose of NSAIDs, outcomes of trials and duration of therapy were quite diverse, which caused difficulties in quantitative analysis.

Results of the search

In the previous search, we identified 57 trials; of these, nine met the inclusion criteria. In this 2013 update search, we identified three more potential trials and all three were excluded. All included studies were double‐blinded RCTs. Four of the six trials of community‐acquired colds were multi‐centre trials.

Included studies

The nine included studies involved 1069 participants suffering from colds. In six studies, 891 participants had community‐acquired colds, and in three studies, 178 participants were experimentally infected with cold viruses. For experimentally infected colds, inoculated populations were analysed. Only 72.5% of experimentally infected participants had cold symptoms. Therefore, we included non‐symptomatic infected participants in this analysis.

Three studies were performed in the USA, four in Japan, and one each in Belgium and Denmark. Trials took place in a total of 154 settings. Most were participants from hospitals, clinics and outpatient departments. One trial involved medical students and university staff. Three trials of experimentally infected colds did not report the trial setting. One trial involved mainly students and two trials reported participants only as volunteers.

Five trials compared NSAIDs with a placebo, three trials compared one NSAID with another, and one trial compared two NSAIDs with a placebo.

Five studies used ibuprofen, two used aspirin and two studies used loxoprofen. Ketoprofen, fenoprofen, fentiazac and naproxen were used in one study. Seven trials used visually identical capsules, one trial used a double‐dummy method and one trial used coded vials. The duration of treatment varied from a single dose to two daily doses for seven days.

Three studies used a general symptom score and five studies used a symptom severity score.

The Characteristics of included studies table includes a summary of the randomisation process, cold acquisition route, inclusion criteria, population, interventions and comparisons, outcome measures, adverse events and methodological qualities.

Excluded studies

We excluded 51 trials: four studies were not randomised or the randomisation allocation was unclear; one study included febrile participants; 46 studies included participants with diagnoses other than common colds (see Characteristics of excluded studiestable).

Risk of bias in included studies

The overall risk of bias in the included studies was mixed, largely due to missing information regarding randomisation procedures. We assessed two studies (Goto 2007; Ryan 1987) as being of high quality.

Allocation

Out of the nine included studies (Goto 2007; Graham 1990; Itoh 1980; Katsu 1993; Nagaoka 1980; Ryan 1987; Sperber 1989; Sperber 1992; Winther 2001), two studies (Goto 2007; Ryan 1987) used a computer‐generated random numbers table to generate the allocation sequence. The remaining studies contained insufficient information about the sequence generation process.

In four studies (Goto 2007; Itoh 1980; Nagaoka 1980; Ryan 1987) the allocation method was adequately concealed. In two Japanese studies (Itoh 1980; Nagaoka 1980) the randomisation process was carried out by two controllers who retained the key codes. In the remaining two studies, treatment was allocated by a third party (Goto 2007), or considered adequately concealed because the single oral dose was administered using a double‐blind method (Ryan 1987).

Blinding

All studies were described as 'double‐blind' and considered 'adequate'; either the active drug and placebo were identical, or an 'identical capsule double‐dummy' method was used.

Incomplete outcome data

Among the included studies, eight (Goto 2007; Graham 1990; Itoh 1980; Nagaoka 1980; Ryan 1987; Sperber 1989; Sperber 1992; Winther 2001) adequately addressed incomplete outcome data. Three experimental rhinovirus cold trials (Graham 1990; Sperber 1989; Sperber 1992) excluded participants who were not infected, in which case the reason for exclusion may be justifiable. In six studies (Itoh 1980; Nagaoka 1980; Ryan 1987; Sperber 1989; Sperber 1992; Winther 2001), the number of withdrawals was zero or very small. One study had insufficient information to permit judgement of 'low risk' or 'high risk' of bias (Katsu 1993).

Selective reporting

All studies were considered as 'unclear' risk of bias as all trials failed to include the study protocol. They had insufficient information to permit a judgement of either 'low risk' or 'high risk' of bias.

Other potential sources of bias

Amongst the included studies, none were stopped early or reported claims of fraudulence against it. One study (Winther 2001) did not contain data to assess the baseline balance. The overall quality of studies was mixed, largely due to missing information regarding randomisation procedures (Figure 1; Figure 2).

Effects of interventions

In total, we identified 37 outcomes. Eight studies assessed effectiveness and five studies assessed adverse effects. Twenty‐one (56.7%) of the 37 outcomes were assessed only by a single trial. Among the 16 outcomes assessed by two trials or more, six outcomes had an I2 statistic of ≥ 50% (overall symptom score, duration of colds, cough score, headache score, chills score and overall side effects).

Outcomes included in the meta‐analyses

One trial (Sperber 1992) reported the daily symptom scores during six post‐challenge days and a six‐day cumulative symptom score. Because other trials reported cumulative symptom scores, we included the cumulative symptom score in the meta‐analysis for comparison.

One trial (Sperber 1989) reported cumulative symptom scores for individual symptoms, such as rhinorrhoea and nasal obstruction, as well as cumulative symptom scores for individual areas (that is, nasal symptom score). To prevent double counting and to compare data, we included only cumulative symptom scores of individual symptoms in the meta‐analysis.

Graham 1990 used aspirin (4 g/day) and ibuprofen (1.2 g/day). Because the dose of ibuprofen was the usual prescribed dose for the common cold and that of aspirin was not, we chose to use the ibuprofen group in the meta‐analysis.

1. Global evaluation of efficacy in the treatment of common cold symptoms

i. Non‐steroidal anti‐inflammatory drugs (NSAIDs) versus placebo

Three trials (Goto 2007; Sperber 1989; Sperber 1992) assessed the total symptom score improvement of NSAIDs on the course of the common cold. The first trial (Sperber 1989) included 40 young adults and compared the effect of ibuprofen at a dose of 200 mg/four times a day for five days with that of a placebo. During six post‐challenge days, the daily total symptom score was not significantly different between the two groups. The second trial (Sperber 1992) included 79 young adults and compared naproxen at a dose ranging from 3.0 to 5.0 g for five days with placebo. The total five‐day symptom score judged by the modified Jackson criteria was reduced by 29% (95% CI 16% to 42%) in the naproxen group compared with the placebo group. The third trial (Goto 2007) included 174 adults and compared the effects of loxoprofen at a dose of 60 mg/twice a day for seven days with placebo. Duration of illness, number of days with limited daily activities and total symptom score were not significantly different between the two groups. We conducted a meta‐analysis of data from the three trials. The results of the pooled analysis were not significant (standardised mean difference (SMD) ‐0.40, 95% confidence interval (CI) ‐1.03 to 0.24, random‐effects model) (Analysis 1.2) and there was heterogeneity (I2 statistic = 83%).

Two trials assessed the duration of colds (Goto 2007; Sperber 1989). The results of the pooled analysis were not significant (mean difference (MD) ‐0.23, 95% CI ‐1.75 to 1.29, random‐effects model) (Analysis 1.5) and there was heterogeneity (I2 statistic = 80%).

One trial assessed the proportion of patients with symptoms of moderate to marked severity (Sperber 1989); no significant effect was detected.

ii. Head‐to‐head comparisons

Three trials involving participants with natural colds assessed the effect of one NSAID compared to other NSAID and ranked the severity of global symptoms on a five‐ to seven‐point scale; all three trials were performed in Japan (Itoh 1980; Katsu 1993; Nagaoka 1980).

Nagaoka 1980, which involved 222 participants, compared fentiazac (300 mg/day) with ibuprofen (600 mg/day). Katsu 1993involved 167 participants and compared loxoprofen (80 mg/day) with ibuprofen (600 mg/day). Itoh 1980 enrolled 184 participants with upper respiratory tract infections and compared aspirin with ketoprofen. Itoh 1980 reported that there was no statistically significant difference between the groups in a subgroup analysis for the population with common colds, but the estimates and the number of participants included in the study population were not reported. Therefore, we could not use this result in a pooled analysis of efficacy.

Marked improvement and moderate to marked improvement (in a global improvement rating) were significant in only one study (Nagaoka 1980).

2. Decrease in the number or duration of individual common cold symptoms

i. NSAIDs versus placebo: analgesic effects

Two trials (Sperber 1992; Winther 2001) measured nine outcomes evaluating the analgesic effects of NSAIDs. The types of NSAIDs and the scale of outcomes differed between these studies.

As mentioned above, Sperber 1992 assessed the effect of naproxen in participants with an experimental cold and reported daily symptom scores and total (five‐day) symptom scores. Winther 2001 enrolled 80 participants with natural colds. The effect of ibuprofen at a dose of 400 mg/three times a day for three days was studied and the severity of symptoms was then ranked on a four‐point scale (not present, mild, moderate, severe) and a three‐day cumulative symptom score was reported.

Firstly, the cumulative throat irritation score was used in two trials (Sperber 1992; Winther 2001). In Sperber 1992, total (five‐day) and daily throat scores were not significantly different between the treatment groups. In Winther 2001, the total throat irritation/pain score was not significantly different between the treatment groups. As expected, the results of the pooled analysis were not significant (SMD ‐0.01, 95% CI ‐0.33 to 0.30, fixed‐effect and random‐effects models) (Analysis 2.2) and there was no heterogeneity.

Secondly, cumulative headache scores were reported in the same two trials (Sperber 1992; Winther 2001). All trials reported that headache scores were significantly lower in the NSAIDs groups than in the placebo groups. In a pooled analysis, NSAIDs significantly reduced headache scores (SMD ‐0.65, 95% CI ‐0.97 to ‐0.32) (Analysis 2.3). The results of fixed‐effect and random‐effects models were the same; there was marginal heterogeneity.

Thirdly, cumulative pain scores in the muscles and joints were also reported in these two trials (Sperber 1992; Winther 2001). In Winther 2001, the pain score in muscles and joints did not differ significantly between the treatment groups. In Sperber 1992, the myalgia score was significantly reduced in the naproxen group. In a pooled analysis, NSAIDs significantly reduced the score for pain in muscles and joints (SMD ‐0.40, 95% CI ‐0.77 to ‐0.03) in fixed‐effect models; there was no heterogeneity.

Fourthly, the two studies assessed a cumulative malaise score (Sperber 1992; Winther 2001). All trials reported that the malaise score was not significantly different between the two treatment groups. However, in a pooled analysis there was a trend towards reduction of malaise (SMD ‐0.29, 95% CI ‐0.6 to 0.03, fixed‐effect and random‐effects models) (Analysis 2.7, Analysis 2.8).

Fifthly, the two studies assessed a cumulative chills score; the results were mixed. One trial reported a significant reduction (Sperber 1992) and another reported a significant increase (Winther 2001). In a pooled analysis, the statistical significance of the difference disappeared and heterogeneity was detected (SMD ‐0.02, 95% CI ‐0.34 to 0.30, P = 0.89, P = 0.0006; I2 statistic = 91.5%) (Analysis 2.9).

The cumulative earache score was significantly reduced in the ibuprofen group compared to the placebo group (Winther 2001).

ii. NSAIDs versus placebo: non‐analgesic effects

Four trials (Graham 1990; Sperber 1989; Sperber 1992; Winther 2001) measured 15 outcomes irrelevant to the analgesic effect. The scales of outcomes were quite diverse. Three trials (Graham 1990; Sperber 1989; Winther 2001) tested ibuprofen and one trial (Sperber 1992) tested naproxen.

Firstly, two trials reported a cumulative cough score (Sperber 1992; Winther 2001). In Sperber 1992, the cumulative cough score was not significant (0.8 and 1.6, naproxen and placebo, respectively), but the daily score was significantly reduced at four days (P < 0.01). Winther 2001 evaluated the cumulative cough score, but there was no difference between the groups. The results of a pooled analysis for cumulative cough score were not significant.

Secondly, two trials evaluated a cumulative sneezing score (Sperber 1992; Winther 2001). In Sperber 1992, the cumulative sneezing score was not significant (1.5 and 2.2, naproxen and placebo, respectively) but daily scores were reduced in the naproxen group at one and four days. The statistically insignificant differences between scores were at two and three days. In Winther 2001, the cumulative sneezing score was significantly reduced in the ibuprofen group, and the result of a pooled analysis supported this effect (SMD ‐0.44, 95% CI ‐0.75 to ‐0.12, the P value of the heterogeneity test was 0.44; the results of fixed‐effect and random‐effects models were the same) (Analysis 3.4). Winther also examined the total number of sneezes and the result was significant.

Three trials studied a cumulative rhinorrhoea score and a cumulative nasal obstruction score, and found no differences between the groups (Sperber 1989; Sperber 1992; Winther 2001).

The proportion of nasal obstruction scores greater than five points (Graham 1990), total mucus weight, total tissue count (Sperber 1989), total number of nose blows, cumulative nasal dryness score, cumulative score for reduced sense of smell, cumulative hoarseness score, cumulative fatigue score and cumulative malaise score were quantified in a single study (Winther 2001) and the results were not significantly different between the treatment groups.

The cumulative nose irritation score, cumulative pain on swallowing score and cumulative eye itching score were also not significantly different between the treatment groups (Winther 2001).

3. Any reported side effects

i. NSAIDs versus placebo: adverse effects

Five trials reported adverse effects. One study (Goto 2007) reported that adverse effects were more frequent in the loxoprofen group (9.5% versus 1.1%, P < 0.05). Otherwise we could not find any evidence of increasing frequency of adverse effects in the active treatment groups. These outcomes included overall side effects, gastrointestinal complaints and other problems such as rash and oedema.

Two trials assessed the overall side effects of NSAIDs and there was moderate heterogeneity (Goto 2007; Sperber 1989). The results of a pooled analysis for overall side effects was significant with a fixed‐effect model (risk ratio (RR) 2.88, 95% CI 1.11 to 7.45, P = 0.03) (Analysis 4.1) but not with a random‐effects model (RR 2.94, 95% CI 0.51 to 17.03) (Analysis 4.2). Three trials reported gastrointestinal adverse effects and found no differences between the groups (Ryan 1987; Sperber 1989; Sperber 1992). Lethargy/drowsiness, feeling hyperactive, feeling more awake, flushed face, difficulty sleeping, light‐headedness and dry mouth were reported in one or two trials and the results were not significantly different between the treatment groups.

Discussion

In summary, if non‐steroidal anti‐inflammatory drugs (NSAIDs) are administered to community‐infected or experimentally infected cold patients, their analgesic effect against pain and irritation induced by the cold is relatively effective, but reports on whether they are helpful in relieving respiratory symptoms, such as coughing and sneezing, are not consistent and the evidence is insufficient.

Despite a comprehensive search, only nine studies met the inclusion criteria, six of which were placebo‐controlled RCTs and three of which were head‐to‐head RCTs. When we evaluated the methodological quality of the included studies using The Cochrane Collaboration's tool for assessing risk of bias (Higgins 2011), the overall quality of studies was mixed, largely due to missing information regarding randomisation procedures. We assessed two studies (Goto 2007; Ryan 1987) as being of high quality. Our outcomes were mainly subjective and blinding of participants may be critical. All nine studies were described as 'double‐blind' and considered 'adequate'.

Among the results used to examine the effect of NSAIDs on the common cold, the ones looking at the analgesic effect evaluated headache, throat irritation, muscle and joint pain, ear pain, malaise and chills. Among them, headache, ear pain and muscle and joint pain showed significant results and malaise showed borderline significance. However, throat irritation was not improved, and chills showed mixed results. For some cases where symptoms did not improve, the reasons were uncertain. Whether the cold was community‐acquired or experimentally infected, the trial quality and dose of NSAIDs could not explain the differences. In the case of throat irritation, if the cold was an infection with a rhinovirus, there was the possibility that the treatment was not effective because throat pain disappeared naturally over a short period of time (Heikkinen 2003). There is also the possibility that the mechanism of throat pain may be different from that of headache and muscle pain. In the case of chills, NSAIDs were obviously effective in one trial, but worsened the symptoms in the other trial. Because chills are known to happen mainly when the fever has lowered, the measure of improvement may be different from the other symptoms and depends on whether there was a fever before the administration of treatment or not. However, because there was no information on the body temperature before starting the treatment in the two trials, we cannot draw a conclusion on this matter. Apart from these two symptoms, NSAIDs improved most of the analgesia‐related symptoms caused by a cold. Therefore, we recommend the use of NSAIDs for these symptoms.

Three trials (Goto 2007; Sperber 1989; Sperber 1992) studied whether NSAIDs had a comprehensive effect on various symptoms caused by the common cold. Two of them (Sperber 1989; Sperber 1992) were conducted with participants whose cold was experimentally infected by a rhinovirus. One of those (Sperber 1992) showed a statistically significant difference in the effect of NSAIDs and when the results of the two studies were merged the results were significant. However, one recently published trial (Goto 2007) reported that the total symptom score showed no significant difference between the two groups. The results of the pooled analysis were not significant and there was heterogeneity, but the reason for this was unclear.

Among the studies two trials examined whether NSAIDs reduced the duration of a cold (Goto 2007; Sperber 1989). The results of the pooled analysis were not significant and there was heterogeneity. NSAIDs did not have any effect on the severity or duration of a cold. Because there were only two trials and the number of subjects in the studies was small, it is hard to draw a definite conclusion about the effects of NSAIDs on the duration of a cold.

One of the current issues related to the administration of NSAIDs for the common cold is whether NSAIDs are helpful in relieving respiratory symptoms such as cough. Many of the studies on the common cold recommend the administration of NSAIDs to ease coughing caused by a cold (Heikkinen 2003; Irwin 2000). The recently published American College of Chest Physicians (ACCP) guidelines recommend the combined administration of first‐generation antihistamine and nasal decongestant or the administration of naproxen for cough caused by a cold (Pratter 2006). Respiratory symptoms examined in this review were cough, nasal discharge and sneezing. The medication was not effective for cough in two trials (Sperber 1992; Winther 2001) and pooled results did not show a significant improvement. None of the three trials (Sperber 1989; Sperber 1992; Winther 2001) showed a significant result for nasal discharge, and pooled results were not significant. However, in the case of sneezing, one trial (Winther 2001) showed a significant improvement and pooled results showed a moderate effect. Considering these results, which differ from existing guidelines, there is no clear evidence that NSAIDs are effective for coughs caused by a cold, or should be recommended in order to ease cough caused by a cold.

NSAIDs draw attention due to their adverse effects. For some NSAIDs, their long‐term use increases the risk of cardiovascular disease (Matchaba 2004) and may cause gastrointestinal side effects (Ofman 2002). The frequency of gastrointestinal side effects increases in proportion to the dose and period of NSAID medication but the risk of gastrointestinal side effects cannot be excluded in short‐term use (Hernández‐Díaz 2000). In trials included in this review, the risk of side effects was not high but it is difficult to conclude that they are not different from placebo in terms of side effects.

In this review, three trials (Itoh 1980; Katsu 1993; Nagaoka 1980) studied which specific NSAIDs were more effective in treating a cold. One study (Nagaoka 1980) found that fentiazac was more effective than ibuprofen. However, this is probably because the dose of ibuprofen used in the trial was 600 mg/day, lower than that used in other trials.

The absence of epithelial destruction during rhinovirus infections has led to the idea that the clinical symptoms of the common cold may not be caused by a direct cytopathic effect of the viruses but instead are primarily caused by the inflammatory response of the host by media such as kinins, leukotrienes and histamines (Heikkinen 2003). Accordingly, NSAIDs are believed to ease not only fever and irritation but also respiratory symptoms such as coughing. However, this was not proven in the review. Further research is needed to examine their effects.

For analgesic effects on a cold, acetaminophen was also frequently used along with NSAIDs. However, in this review, we did not examine which of the medications was superior in terms of effect and safety. Further research is needed to evaluate this.

Major limitations of this review are that the results of the research are quite diverse and the number of studies for one result is quite small. For this reason, it is somewhat difficult to draw clear conclusions.

In conclusion, NSAIDs are recommended for relieving irritation or pain caused by a cold but the notion that NSAIDs are effective in relieving respiratory symptoms such as cough and nasal discharge needs more solid evidence.

Summary of main results

If NSAIDs are administered to community‐infected or experimentally infected cold patients, their analgesic effect against pain and irritation induced by the cold is somewhat effective but reports on whether they are helpful in relieving respiratory symptoms such as coughing and sneezing are not consistent and the evidence is insufficient.

Overall completeness and applicability of evidence

The trials included in the analyses involved mainly young adults of both sex. Therefore the results of these trials may not be applicable to children and older people.

Quality of the evidence

We did not assess the quality of evidence using GRADE methodology but the quality of evidence may be estimated at 'low' to 'moderate' because of imprecision and risk of bias of the evidence.

Potential biases in the review process

Among the analgesic effect outcomes of NSAIDs, headache, pain in muscles and joints, and earache were statistically significant. However, these were mainly based on only two trials.

Agreements and disagreements with other studies or reviews

Some studies (Heikkinen 2003; Irwin 2000) and ACCP guidelines (Pratter 2006) recommend administration of NSAIDs for coughs caused by a cold. However, this review concluded that there is no clear evidence that NSAIDs are effective for coughs caused by a cold.