Corticosteroids for the common cold
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To compare corticosteroids versus usual care for the common cold on clinical response rates in children and adults.
Background
The common cold is the conventional term for upper respiratory tract viral infections which are benign and self‐limiting. Over 500 million patients develop colds in a year in the United States (Fendrick 2003), resulting in 22 million school days lost (Adams 1999) and an annual lost productivity of almost $25 billion (Bramley 2002).
Description of the condition
The well recognised symptoms of a cold include nasal obstruction, rhinorrhoea, sneezing, sore throat and, on occasion, mild fever, headache and myalgia. The most common causative agent is the rhinovirus (Makela 1998), although several different viral families have been implicated, and bacterial infection can give rise to the same symptoms (Kaiser 1996). Rhinoviral infection begins with deposition of virus on the nasal epithelium via airborne droplets and by hand from fomites. The inflammatory response of nasal mucosa to the viral antigens, with vasodilation and increased vascular permeability, results in sneezing, nasal congestion and rhinorrhoea.
Description of the intervention
Management options for the common cold currently focus on symptom alleviation. This includes using antihistamines, which have at best a slight clinical benefit (De Sutter 2003) or decongestants, which produce a small decrease in subjective symptoms (Taverner 2007). Whilst both of these therapies are targeting the effects of the inflammatory response of the nasal mucosa to the virus, this inflammatory response could also be modulated by the use of corticosteroids, which inhibit the generation of proinflammatory cytokines in nasal epithelium (Mygind 2001).
How the intervention might work
Corticosteroids have been demonstrated to increase the likelihood of resolution or improvement of symptoms in acute sinusitis (Zalmanovici 2007) as well as in viral croup (Russell 2004). Their anti‐inflammatory actions on the nasal mucosa may also reduce the symptoms and duration of the common cold.
Objectives
To compare corticosteroids versus usual care for the common cold on clinical response rates in children and adults.
Methods
Criteria for considering studies for this review
Types of studies
Randomised controlled trials (RCTs) comparing corticosteroids to placebo or to standard clinical management (for example, conservative measures such as pain relief) for the common cold.
Types of participants
Children and adults with the common cold, defined by clinical diagnosis. We will exclude trials where a definitive diagnosis of another upper respiratory condition is present (for example, influenza and sinusitis).
Types of interventions
Oral or inhaled corticosteroids versus standard clinical care or placebo in the control group.
Trials reporting combined interventions will be included if they allow a direct comparison between corticosteroids and usual care for the common cold and are unconfounded. By unconfounded, we mean studies where the two groups were not treated differently, except for the provision of steroids to one group. Confounding can occur by the use of a different medication regime (for example, paracetamol) for one of the two groups. If the two groups were treated unequally apart from the corticosteroids, we will exclude them.
Types of outcome measures
Primary outcomes
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Proportion of participants with resolution or improvement of symptoms (individual and global) within one month.
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Time lapse before resolution of symptoms.
Secondary outcomes
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Adverse events necessitating discontinuation of treatment.
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Relapse rates.
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Microbiological consequences, for example, length of shedding of virus from nasopharyngeal secretions.
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Treatment for secondary infections.
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Quality of life measures and economic costs.
Search methods for identification of studies
Electronic searches
We will search the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, latest issue) which includes the Acute Respiratory Infections (ARI) Group's Specialised Register, the Database of Reviews of Effects (DARE) and the NHS Health Economics Database; MEDLINE (1966 to present); and EMBASE (1974 to present).
The MEDLINE search will be combined with the Cochrane Highly Sensitive Search Strategy for identifying RCTs (Lefebvre 2008). See Appendix 1 for the MEDLINE and CENTRAL search strategy, and Appendix 2 for the EMBASE search strategy.
Searching other resources
To increase the yield of relevant study references, we will search the reference lists of all identified studies, and contact experts in the field where relevant.
Data collection and analysis
Selection of studies
Two review authors (GH, MT) will independently review the title and abstracts of the electronic search results. One review author (GH) will obtain full text articles. Two review authors (GH, MT) will independently review full text articles for their inclusion in the review. A third review author (CH) will resolve disagreements by discussion.The review authors will not be blind to the journal of origin, the authors, the institutions or the magnitude of results.
Data extraction and management
Two review authors (GH, MT) will independently extract data from included trials. Data extracted and presented will include: author, publication year, journal, participants (numbers, duration of illness, demographics, characteristics of the disease, etc.), intervention (type of intervention, and duration), results (outcome measures, effect, statistical significance, adverse effects). We will independently enter data into an extraction template and agreement will be checked. A third review author (CH) will discuss and resolve disagreements. A statistician (RP) will independently review all data extracted from original publications to verify the quality of methods and analysis used. We will write to the trial authors for clarification of data where information is lacking.
Assessment of risk of bias in included studies
Two review authors (GH, MT) will independently assess the methodological quality, with disagreements documented and resolved by discussion with a third review author (CH). The specific aspects of methodological quality assessed will include: allocation concealment, randomisation, blinding, treatment adherence, percentage participation and comparability of groups on baseline characteristics. We will report the quality using the Cochrane Collaboration's tool for assessing risk of bias. We will incorporate this assessment into the interpretation of results by performing sensitivity analyses and excluding studies of the lowest quality.
Measures of treatment effect
We will express dichotomous outcomes as risk ratios (RR) and calculate 95% confidence intervals (CIs). We will express continuous variables as mean difference (MD) if reported on the same scale or as a standardised mean difference (SMD) if reported using different continuous scales, and calculate 95% CIs.
Dealing with missing data
If significant drop‐out of participants is noted we will conduct an intention‐to‐treat analysis. Where data are missing we will attempt to contact the original trial authors. We will analyse only the available data and discuss the impact of the missing data on our findings.
Assessment of heterogeneity
We will use the I2 statistic (Higgins 2003) to measure the level of statistical heterogeneity for each outcome. Where no heterogeneity is present, we will perform a fixed‐effect meta‐analysis. Where substantial heterogeneity (I2 above 50%) is detected, we will consider possible explanations for this and, where applicable, use a random‐effects model and consider not combining the results and present a descriptive analysis.
Assessment of reporting biases
We will assess reporting biases using funnel plots where we have sufficient trials, and consider reasons for asymmetry if it is noted.
Subgroup analysis and investigation of heterogeneity
We will use subgroup analyses to explore effect differences by group and heterogeneity found in the primary analyses. We will consider subgroup analyses for the following areas.
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Child/adult.
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Type and route of corticosteroid.
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Duration of treatment.
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Rhinovirus positive nasal cultures.
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Type of control ‐ placebo/standard clinical care.
Sensitivity analysis
Where necessary, we will perform a sensitivity analysis by removing single trials to investigate the extent to which they contribute to any heterogeneity, particularly looking at baseline characteristics.
