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:
- One of either nasal blockage/obstruction/congestion and/or nasal
discharge (anterior/posterior nasal drip)
- and either facial pain/pressure and/or reduction or loss of sense of
smell
and additionally:
- endoscopic signs of: polyps and/or mucopurulent discharge primarily
from middle meatus; and/or oedema/mucosal obstruction primarily in
middle meatus
- and/or CT changes: mucosal changes within the ostiomeatal complex
and/or sinuses
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
- Prior history of recurrent acute or chronic rhinosinusitis.
- Any other nose/sinus disorders e.g. allergic rhinitis (hayfever).
- Active medical problems that have required a hospital visit within the
last 12 months.
Exclusion Criteria for Both
Groups
- Patients/controls unable to comprehend written English.
- Patients/controls under the age of 18 years.
Quantitative Variables and
Bias
The detailed questionnaire can be seen in appendix 1. The variables
considered here in this updated analysis include:
- The presence of comorbidities including asthma, chronic obstructive
pulmonary disease (COPD), bronchiectasis, diabetes, hypothyroidism,
autoimmune diseases, immunodeficiency and ciliary dysmotility
- Quality of life as recorded by the domains of the SF-36.
- Socioeconomic variables including mean index of multiple deprivation
(IMD), mean household income, household occupancy and education level.
- 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:
- Comorbidities – comparisons using logistic regression and adjusting
for age and sex of the rate of:
- asthma
- COPD
- bronchiectasis
- URTIs per year
- diabetes
- hypothyroidism
- immunodeficiency
- autoimmune diseases
- ciliary dysmotility
- 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.
- Socio-economic status:
- Mean index of multiple deprivation (IMD) using regression, adjusting
for age and sex
- Mean household income using regression, adjusting for age and sex
- Median household occupancy using a Mann-Whitney test
- 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.
- Lifestyle and environmental exposure were compared using a Chi-Squared
test
- Comparison of alcohol consumption
- Comparison of smoking rates
- 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