Methods

This study has been reported in accordance with the STROBE statement guidelines for the reporting of observational studies. The study was sponsored by the University of East Anglia (UEA) and funded by the Anthony Long and Bernice Bibby Trusts. Ethical approval was granted by the Oxford C Research Ethics Committee (Ref: 07/H0606/100).

Study Design

The CRES was a prospective, questionnaire-based, case-control study conducted between October 2007 and September 2013 at thirty tertiary/secondary care sites across the United Kingdom. Patients with diagnosed CRS alongside healthy control subjects were asked to complete a single, study-specific questionnaire, capturing a variety of demographic and socio-economic variables, environmental exposures and medical co-morbidities (See appendix 1).

Participants and Data Sources

Prospective participants were identified for recruitment at ENT outpatient clinics at 30 participating centres. Patients with CRS were examined by an ENT clinician and classified into CRS phenotypes (CRSwNPs, CRSsNPs or allergic fungal rhinosinusitis (AFRS) as per EPOS 2012 criteria(22) (see CRS participant section below). Healthy controls were recruited from family members of patients attending ENT clinics as well as members of hospital staff at recruitment sites.
Questionnaires were completed during the clinic visit or taken home to be completed and returned by prepaid post. No participant identifiable data was captured therefore consent was not required although it was implied through return of the questionnaire. Returned questionnaires were scanned and the data imported into in an electronic database in Microsoft Excel. Records in the database were compared to physical copies of the questionnaires by two members of the research team to ensure accuracy and consistency between the two.
All CRS participants and healthy controls were required to meet the inclusion/ exclusion criteria outlined below:

CRS Participants

Inclusion Criteria
Criteria for diagnosis of CRS with or without polyps (EPOS 2012 guidelines – as were relevant at the time of study )(22)
At least two symptoms must be present for at least 12 weeks and include:
and additionally:
Patients were then classified as having chronic rhinosinusitis without polyps (CRSsNPs), chronic rhinosinusitis with nasal polyps (CRSwNPs) or allergic fungal rhinosinusitis (AFRS); patients with the latter were not included in this analysis.

Healthy Control Participants

Exclusion Criteria

Exclusion Criteria for Both Groups

Quantitative Variables and Bias

The detailed questionnaire can be seen in appendix 1. The variables considered here in this updated analysis include:
  1. The presence of comorbidities including asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, diabetes, hypothyroidism, autoimmune diseases, immunodeficiency and ciliary dysmotility
  2. Quality of life as recorded by the domains of the SF-36.
  3. Socioeconomic variables including mean index of multiple deprivation (IMD), mean household income, household occupancy and education level.
  4. Lifestyle factors including smoking, alcohol and urban or non-urban domestic location

Sample Size Calculation

The sample size calculation was based on the original primary outcome of the study which was to look for common associations between socioeconomic factors and CRS11. For socio−economic scores, the standard approach is to compare the proportion of subjects in the lower social classes to eve­ryone else. In order for the study to have 80% power to detect a difference of 10% in “low social class” between controls and CRS participants, assuming a 30% rate in the CRS participants, with approxi­mately 5 CRS participants to 1 control patient, 965 CRS participants and 193 controls were required(19).

Statistical Methods

Patient demographics were summarised by CRS phenotype status using mean and standard deviation for continuous variables and the number and percentage for categorical variables. For the comparisons between the two phenotypes we planned the following analyses:
  1. Comorbidities – comparisons using logistic regression and adjusting for age and sex of the rate of:
  2. asthma
  3. COPD
  4. bronchiectasis
  5. URTIs per year
  6. diabetes
  7. hypothyroidism
  8. immunodeficiency
  9. autoimmune diseases
  10. ciliary dysmotility
  11. Quality of life: Comparing the mean SF-36 Score, its subscales (vitality, physical function, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning and mental health) and its summary score (physical health and mental health) between the two groups using regression, adjusting for age and sex.
  12. Socio-economic status:
  13. Mean index of multiple deprivation (IMD) using regression, adjusting for age and sex
  14. Mean household income using regression, adjusting for age and sex
  15. Median household occupancy using a Mann-Whitney test
  16. Education level using a Chi-squared test for individual levels and an odds ratio for grouped levels of GSCE/A-Level and Degree/Higher Degree.
  17. Lifestyle and environmental exposure were compared using a Chi-Squared test
  18. Comparison of alcohol consumption
  19. Comparison of smoking rates
  20. Comparison of the percentage of people who live in a village
All analyses were conducted using Stata MP 16.0.

Results

Study Participants

A total of 1535 questionnaires were returned with 1470 considered eligible for inclusion after removal of duplicates and questionnaires with missing data; only CRSwNP and CRSsNP cases were included in this analysis (see figure 1). This analysis is therefore based on the 1204 CRS participants who completed the relevant parts of the questionnaire. The overall response rate of those identified to take part in the study was 66% of those distributed.

Descriptive Data

For the purpose of this analysis, participants with AFRS were not analysed due to smaller numbers of cases in the database. As such, there were 553 participants with CRSsNPs and 651 participants with CRSwNPs. The mean age of CRSsNP participants was 52 years (range 18-84) and of CRSwNP participants was 56 years (range 18-102). CRSsNP and CRSwNP participants were 53% and 31% female respectively; 65 and 77 participants in those two phenotypes respectively did not declare their sex.

Primary Outcome Data and Main Results