Acute respiratory infection (ARI), including the common cold and influenza, is the most prevalent of human illnesses. Surveys report that over 70% of people experience at least one cold in a given year, with adults averaging 2 or 3 colds and young children averaging as many as 4 to 6 colds per year. More than 45 million days of work and 22 million days of school are lost as a result. In the U.S. alone, more than $2 billion is spent out of pocket annually on cold remedies, with more than $7 billion in sick pay losses attributable to non-influenza ARI. One study estimated annual direct costs at $17 billion and indirect costs at $22.5 billion, for a total economic impact of close to $40 billion. ARI is the most important cause of asthma exacerbation, and often leads to otitis media, sinusitis, bronchitis or pneumonia. For those at increased risk, such as the very old, those with multiple illnesses, or the immune compromised, ARI may be fatal.
Despite the fact that more than a thousand randomized controlled trials have spent many millions of dollars testing dozens of cold remedies, prior to WURSS there was no well-developed, standardized and validated measure for assessing the symptomatic and functional impact of ARI.
In order to develop and validate such an instrument, we chose to combine qualitative and quantitative methodologies, including cognitive interview and focus group. A published description of the development process is available:
We then went on to prospectively validate the WURSS-44, aiming for assessment of reliability, responsiveness, importance-to-patients, and convergent validity. Over 18 months some 149 people with colds filled out the WURSS-44, the Jackson scale and the SF-8 (24-hour recall version) each day from the beginning of their colds until their symptoms had resolved, generating a data set of 1,681 person-days. Using importance-to-patient and responsiveness as guides, a subset of items was selected for the WURSS-21..
A third paper comparing WURSS with laboratory-based measures was published next. Using data from an NIH-funded randomized controlled trial in an induced cold experimental rhinovirus infection model, this paper compares WURSS scores with quantitative viral culture, nasal mucus weight, neutrophil count, interleukin-8 and glutathione, and with the self-report questionnaire scores from the Jackson cold scale and the SF-8 general health-related quality-of-life instrument.
A fourth manuscript detailing anchor-based and distribution-based methods of assessing important difference and responsiveness was next made available:
Our next project was to complete a prospective independent evaluation of the WURSS-21, as compared to the WURSS-44, along with several other comparator measures. Those results were published in 2009:
Aiming for a version to assess influenza-like illness, we added items on fever, headache and body ache from the WURSS-44 to the WURSS-21, making the WURSS-24. We recommend this version for studies of influenza, influenza-like-illness, and COVID-19.
Next, we developed the short-form WURSS-11 using factor analysis, and by excluding items with redundancy and floor effects. This shortest version of WURSS will be quicker and easier to use, and may increase response rates among research participants.
We took a look at whether doctors or patients could predict the course of new-onset colds, and found that while they couldn’t, the WURSS did, to a limited extent:
Using a data set from 811 people, we analyzed the association of symptoms assessed by WURSS with inflammatory biomarkers, and found that nasal symptoms correlated more closely with interleukin-8 and nasal neutrophil count than did other symptoms and functions:
In another project, we used item response theory and Rasch modelling to evaluate WURSS data, and found strong support for the recommended scoring method of simply summing all WURSS items (excluding the first and last items, which assess global illness and change-over-time):
We have used the WURSS-21 as the primary outcome measure in three NIH-funded randomized clinical trials:
There are no perfect definitions of “common cold,” “upper respiratory tract infection,” “acute respiratory infection,” “influenza-like illness” or similar terms. Researchers, however, need definitions in order to implement protocols. We have found the following to be useful:
The beginning of each common cold acute respiratory infection (ARI) illness episode is defined by: 1) answering “Yes” to either: “Do you think you have a cold?” or “Do you think you are coming down with a cold?” AND 2) reporting at least 1 of 4 cold symptoms (or synonyms): nasal discharge (runny nose); nasal obstruction (plugged or congested); sneezing; or sore (scratchy) throat, AND 3) scoring at least 2 points on the Jackson scale. The Jackson score is calculated by summing 8 symptom scores (sneezing, headache, malaise, chilliness, nasal discharge, nasal obstruction, sore throat and cough), rated as 0=absent, 1=mild, 2=moderate, and 3=severe. In order for these symptoms to be classified as an ARI illness episode (and analyzed as such), at least 2 days in a row must meet these criteria. From the first day of ARI illness and forward each participant fills out a daily WURSS until they answer “No” to the question “Do you think that you are still sick with this respiratory infection?” for 2 days in a row. The last day the participant answers “Yes” and fills out a WURSS instrument will be the last day classified as ARI illness.
Daily WURSS summary scores are calculated by summing scores of individual item scores, excluding the first and last items, which have categorically different reference domains, and are analyzed separately. Summary scores of ARI illness episodes are calculated by summing daily scores, or by trapezoidal approximation, or by other methods as advised by the study statistician. Imputation of missing data may be useful. Data from individual items or groups of items can be analyzed separately, depending on research questions. Each study has its own aims and methods. Adjusting the Jackson criteria threshold for ARI illness definition may be advisable. Excluding allergy and other illnesses with cold-like symptoms is usually recommended. An experienced multidisciplinary team and rigorous peer review is almost always a good idea.
We’re not the only ones to use WURSS. Numerous investigators from around the world have selected WURSS for their research and/or education work. The list of registered WURSS users represents more than 400 institutions in more than 50 countries.
L. Spence, W. J. Brown, D. B. Pyne, M. D. Nissen, T. P. Sloots, J. G. McCormack, A. S. Locke, and P. A. Fricker. Incidence, etiology, and symptomatology of upper respiratory illness in elite athletes.Med.Sci.Sports Exerc. 39 (4):577-586, 2007.
M. J. Walter, M. Castro, S. J. Kunselman, et al.. Predicting worsening asthma control following the common cold.Eur.Respir.J. 32 (6):1548-1554, 2008.
S. A. Heinz, D. A. Henson, M. D. Austin, F. Jin, and D. C. Nieman. Quercetin supplementation and upper respiratory tract infection: A randomized community clinical trial.Pharmacol.Res. 62 (3):237-242, 2010.
D. C. Nieman, D. A. Henson, M. D. Austin, and W. Sha. Upper respiratory tract infection is reduced in physically fit and active adults.Br.J.Sports Med., 2010.
J. S. Byun, S. Y. Yang, I. C. Jeong, K. E. Hong, W. Kang, Y. Yeo, and Y. C. Park. Effects of So-cheong-ryong-tang and Yeon-gyo-pae-dok-san on the common cold: randomized, double blind, placebo controlled trial.J.Ethnopharmacol. 133 (2):642-646, 2011.
S. Y. Yang, W. Kang, Y. Yeo, and Y. C. Park. Reliability and validity of Wisconsin Upper Respiratory Symptom Survey, Korean version.J.Epidemiol. 21 (5):313-318, 2011.
E. Tiralongo, R. A. Lea, S. S. Wee, M. M. Hanna, and L. R. Griffiths. Randomised, double blind, placebo-controlled trial of echinacea supplementation in air travellers. Evidence Based Complement Alternat Med. 2012:417267, 2012.
D. R. Murdoch, S. Slow, S. T. Chambers, L. C. Jennings, A. W. Stewart, P. C. Priest, C. M. Florkowski, J. H. Livesey, C. A. Camargo, and R. Scragg. Effect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled trial. JAMA 308 (13):1333-1339, 2012.
J. Guay, P. Champagne, P. Guibord, and J. Gruenwald. The efficacy and safety of a patent pending combination of ginger and goldenrod extracts on the management of cold symptoms: A randomized, double-blind controlled trial. Food and Nutrition Sciences 3:1651-1657, 2012.
J. Scherr, D. C. Nieman, T. Schuster, J. Habermann, M. Rank, S. Braun, A. Pressler, B. Wolfarth, and M. Halle. Nonalcoholic beer reduces inflammation and incidence of respiratory tract illness. Med Sci Sports Exerc. 44 (1):18-26, 2012.
B. K. McFarlin, K. C. Carpenter, T. Davidson, and M. A. McFarlin. Baker’s yeast www glucan supplementation increases salivary IgA and decreases cold/flu symptomatic days after intense exercise.J.Diet.Suppl 10 (3):171-183, 2013.
D. C. Nieman, B. Luo, D. Dreau, D. A. Henson, R. A. Shanely, D. Dew, and M. P. Meaney. Immune and inflammation responses to a 3-day period of intensified running versus cycling.Brain Behav.Immun., 2013.
Y. Hirose, Y. Yamamoto, Y. Yoshikai, and S. Murosaki. Oral intake of heat-killed Lactobacillus plantarum L-137 decreases the incidence of upper respiratory tract infection in healthy subjects with high levels of psychological stress. J.Nutr.Sci. 2:e39, 2013.
H. G. Ferrari, C. A. Gobatto, and F. B. Manchado-Gobatto. Training load, immune system, upper respiratory symptoms and performance in well-trained cyclists throughout a competitive season. Biol.Sport 30 (4):289-294, 2013.
S. D. Youngstedt, G. Jean-Louis, R. R. Bootzin, D. F. Kripke, J. Cooper, L. R. Dean, F. Catao, S. James, C. Vining, N. J. Williams, and M. R. Irwin. Chronic moderate sleep restriction in older long sleepers and older average duration sleepers: a randomized controlled trial. Contemp.Clin.Trials 36 (1):175-186, 2013.
C. G. Freitas, M. S. Aoki, C. A. Franciscon, A. F. Arruda, C. Carling, and A. Moreira. Psychophysiological responses to overloading and tapering phases in elite young soccer players. Pediatr.Exerc.Sci. 26 (2):195-202, 2014.
Goodall EC, Granados AC, Luinstra K, Pullenayegum E, Coleman BL, Loeb M, Smieja M. Vitamin D3 and gargling for the prevention of upper respiratory tract infections: a randomized controlled trial. BMC Infect Dis. 2014;14:273.
V. F. Milanez, S. P. Ramos, N. M. Okuno, D. A. Boullosa, and F. Y. Nakamura. Evidence of a Non-Linear Dose-Response Relationship between Training Load and Stress Markers in Elite Female Futsal Players.J.Sports Sci.Med. 13 (1):22-29, 2014.
V. Grabs, D. C. Nieman, B. Haller, M. Halle, and J. Scherr. The effects of oral hydrolytic enzymes and flavonoids on inflammatory markers and coagulation after marathon running: study protocol for a randomized, double-blind, placebo-controlled trial.BMC.Sports Sci.Med.Rehabil. 6 (1):8, 2014.
G. Duijker, A. Bertsias, E. K. Symvoulakis, J. Moschandreas, N. Malliaraki, S. P. Derdas, G. K. Tsikalas, H. E. Katerinopoulos, S. A. Pirintsos, G. Sourvinos, E. Castanas, and C. Lionis. Reporting effectiveness of an extract of three traditional Cretan herbs on upper respiratory tract infection: results from a double-blind randomized controlled trial. J.Ethnopharmacol. 163:157-166, 2015.
L. C. Denlinger, T. S. King, J. C. Cardet, etal. Vitamin D Supplementation and the Risk of Colds in Patients with Asthma. Am.J Respir Crit Care Med. 193 (6):634-641, 2016.
E. Tiralongo, S. S. Wee, and R. A. Lea. Elderberry Supplementation Reduces Cold Duration and Symptoms in Air-Travellers: A Randomized, Double-Blind Placebo-Controlled Clinical Trial. Nutrients. 8 (4), 2016.
Sessa A, Voelker M. Aspirin plus Vitamin C Provides Better Relief than Placebo in Managing the Symptoms of the Common Cold. J Health Care Prev. 2017;1(102):2.
Bang MR, Kim JH, Min SY. Clinical effectiveness of the Sanfu herbal patch at acupoints for respiratory diseases including otitis media in children: A pilot before-and-after study. European Journal of Integrative Medicine. 2017;10:1-7.
Jayadevappa R, Cook R, Chhatre S. Minimal important difference to infer changes in health-related quality of life—a systematic review. J Clin Epidemiol. 2017;89:188-198.
Moraes H, Aoki MS, Freitas C, Arruda A, Drago G, Moreira A. SIgA response and incidence of upper respiratory tract infections during intensified training in youth basketball players. Biol Sport. 2017;34(1):49.
Kroll JL, Werchan CA, Reeves AG, Bruemmer KJ, Lippert AR, Ritz T. Sensitivity of salivary hydrogen sulfide to psychological stress and its association with exhaled nitric oxide and affect. Physiol Behav. 2017;179:99-104.
Barrett B, Hayney MS, Muller D, et al. Meditation or exercise for preventing acute respiratory infection (MEPARI-2): A randomized controlled trial. PLoS One. 2018;13(6):e0197778.
Calton JT, Willis AL, Calton JB, Chang EH. Symptom severity from RV infections are increased in those with unified airway disease. J Allergy Clin Immunol. 2018;141(2):AB91.
Tritto AC, Amano MT, De Cillo ME, et al. Effect of rapid weight loss and glutamine supplementation on immunosuppression of combat athletes: a double-blind, placebo-controlled study. Journal of exercise rehabilitation. 2018;14(1):83.
Shimizu Y, Ito Y, Yui K, Egawa K, Orimo H. Intake of 25-hydroxyvitamin D3 reduces duration and severity of upper respiratory tract infection: A randomized, double-blind, placebo-controlled, parallel group comparison study. J Nutr Health Aging. 2018;22(4):491-500.
Ritz T, Trueba AF, Vogel PD, Auchus RJ, Rosenfield D. Exhaled nitric oxide and vascular endothelial growth factor as predictors of cold symptoms after stress. Biol Psychol. 2018;132:116-124.
Antualpa K, Aoki MS, Moreira A. Intensified training period increases salivary IgA responses but does not affect the severity of upper respiratory tract infection symptoms in prepuberal rhythmic gymnasts. Pediatr Exerc Sci. 2018;30(2):189-197.
Braido F, Baiardini I, Canonica GW. Patient-reported outcomes in asthma clinical trials. Curr Opin Pulm Med. 2018;24(1):70-77.
Stolz D, Hirsch HH, Schilter D, et al. Intensified therapy with inhaled corticosteroids and long-acting β2-agonists at the onset of upper respiratory tract infection to prevent chronic obstructive pulmonary disease exacerbations. A multicenter, randomized, double-blind, placebo-controlled trial. Am J Respir Crit Care Med. 2018;197(9):1136-1146.
Jiwa M, Krejany CJ, Kanjo E, Leeb A, Peters IJ. Symptom profile of patients receiving antibiotics for upper respiratory tract infections in general practice: an observational study using smartphone technology. Fam Pract. 2019.
Altman MC, Gill MA, Whalen E, et al. Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children. Nat Immunol. 2019;20(5):637-651.
Ramalingam S, Graham C, Dove J, Morrice L, Sheikh A. A pilot, open labelled, randomised controlled trial of hypertonic saline nasal irrigation and gargling for the common cold. Sci Rep. 2019;9(1):1015.
Dharsono T, Rudnicka K, Wilhelm M, Schoen C. Effects of yeast (1, 3)-(1, 6)-beta-glucan on severity of upper respiratory tract infections: a double-blind, randomized, placebo-controlled study in healthy subjects. J Am Coll Nutr. 2019;38(1):40-50.
de Sousa Oliveira L, Dos TSR, Schoenfeld B, Machado FM, Prestes J. Oxidative stress, inflammation, psychological status, and severity of respiratory infections are negatively affected during the pre-contest period in amateur bodybuilders. Applied physiology, nutrition, and metabolism= Physiologie appliquee, nutrition et metabolisme. 2019;44(5):468-476.
Kwah J, Benjamin MR, Fischer S, et al. Respiratory Virus Detection in Nasal Lavage Fluid of Chronic Rhinosinusitis Patients During Acute Exacerbations. J Allergy Clin Immunol. 2019;143(2):AB86.
Anapurapu S, Bonagoni A, Hooper W, et al. Clinical efficacy and safety evaluation of a novel seawater-based hypertonic solution in common cold patients. In: Eur Respiratory Soc; 2019.
Ritz T, Werchan CA, Kroll JL, Rosenfield D. Beetroot juice supplementation for the prevention of cold symptoms associated with stress: A proof-of-concept study. Physiol Behav. 2019;202:45-51.
Somerville V, Gill ND, Ross A, Braakhuis A. Upper respiratory illness in different tiers of rugby union. Sport Sciences for Health. 2019;15(1):197-205.
Silvestre JC, Gianoni R, Esteves G, Lambertucci R, Zagatto AM, Azevedo P. Beta-alanine Supplementation Neither Reduce the Oxidative Stress nor Improve Physical Performance of Volleyball Athletes. 2019.
Ahmadi S, Brietzke C, Silveira R, et al. Aspects of physical training related with upper respiratory tract infections: a review. Manual Therapy, Posturology & Rehabilitation Journal. 2019;16:0-0.
Salahi N, Mirkarimi S, Fares S, et al. A biomarker for obstructive sleep apnea in chronic rhinosinusitis. J Allergy Clin Immunol. 2019;143(2):AB86.
Sundell N, Andersson L-M, Brittain-Long R, et al. PCR detection of respiratory pathogens in asymptomatic and symptomatic adults. J Clin Microbiol. 2019;57(1):e00716-00718.
Jiwa M, Krejany CJ, Kanjo E, Leeb A, Peters IJ. Symptom profile of patients receiving antibiotics for upper respiratory tract infections in general practice: an observational study using smartphone technology. Fam Pract. 2019;36(5):560-567.
Stolz D, Papakonstantinou E, Grize L, et al. Time-course of upper respiratory tract viral infection and COPD exacerbation. Eur Respir J. 2019;54(4):1900407.
Kim K-I, Hong M, Park Y-C, et al. Herbal medicines (Eunkyosan and Samsoeum) for treating the common cold: a protocol for a randomized, placebo-controlled, multicenter clinical trial. Integrative Medicine Research. 2020;9(1):48-53.
Please let us know of the results of your WURSS-related work, and please alert us to any relevant publications. Contact: email@example.com