METHODS
Study design and
participants
In the international multi-centre (Austria, France, and Italy)
cross-sectional AIS Life + study, conducted between 2013 and 2014, we
enrolled participants suffering from nasal allergy. A convenient sample
of individuals with an active condition of pollen-induced AR was
selected from pre-existing epidemiological study databases or through
web advertisement (Pisa, Italy), clinics of general practitioners
(Paris, France) or public health database and pulmonary clinics (Vienna,
Austria) and invited to participate in this epidemiological survey. All
potential participants were administered a screening questionnaire
through a telephone interview to check whether they were eligible for
the study. We included individuals who: 1) were adults (≥ 18 years of
either sex); 2) reported allergic rhinitis diagnosis/symptoms or
positive clinical tests to pollen in the last 12 months; 3) spent most
of the week (at least 5 days/week) living, studying, or working in the
areas where this study was conducted; and 4) were not treated with
allergen immunotherapy over the previous 6 years.
The study was approved by the ethics committees of the participating
centres in Italy (Ethics Committee of University-Hospital of Pisa;
Protocol No. 14248) and in Austria (Berlin Charite University Ethics:
EA1/119/12), and signed informed consents were obtained from all the
participants before recruitment. In France, the approval by an external
ethic committee was declared as not applicable at that time: instead,
the study was approved by the Hospital ethic committee, by the National
Committee for Information Management on Medical Research (Comite´
Consultatif sur le Traitement de l’Information en Matière de Recherche
dans le domaine de la sante´ ) and by the National Commission on
Informatics and Health (CNIL, Commission Nationale Informatique et
Liberte´ ). In France, the CNIL approved in 2016 that all data acquired
prior to 2016, without the previous need of an authorization of an Ethic
Committee, could still be utilized. In any case, patients were seen in
the frame of routine care (“soins courants ”). The AIS study was
conducted according to the Declaration of Helsinki and reported as per
the Strengthening the Reporting of Observational Studies in Epidemiology
(STROBE) guidelines18.
Instruments and
variables
A standardized health questionnaire was administered to all eligible
individuals in order to obtain information on their demographic
characteristics (age, gender, body mass index [BMI], level of
education), and potential risk factors (smoking status, exposure to
second-hand smoke, and drug consumption), on symptoms/diagnosis of AR
and asthma, disease severity level, as well as on previous clinical
tests (spirometry, skin prick test and serum level of immunoglobulin E
[IgE]).
The health-related quality of life (HRQoL) of the participants was
assessed using a modified version of the validated RHINASTHMA
questionnaire (the higher the score, the lower the HRQoL), i.e., the
only available instrument that allows evaluating the concomitant impact
of AR and asthma on HRQoL19. This 30-item
questionnaire provides individual scores for upper airways, lower
airways, respiratory allergy impact, and a composite score (the Global
Summary [GS] score, which indicates the overall impact of the
disease). The details of the instrument and the scoring system can be
found elsewhere19. Patients used a five-point Likert
scale (’not at all’, ’a little’, ’fairly’, ’much’, ’very much’) to
indicate the extent to which they were bothered by each AR and asthma
during the year preceding the completion of the questionnaire. These
responses are then converted into scores, from 0 to 100, with larger
scores corresponding to worse HRQoL. A RHINASTHMA-GS score from 0 to 20,
indicating minimal or absent disease impact on patient life, was
considered reflective of optimal HRQoL.
The control of AR and asthma was evaluated by a modified version of the
Control of Allergic Rhinitis/Asthma Test (CARAT) (the higher the score,
the higher the disease control)20,21. CARAT is a
10-item questionnaire containing information about the frequency of
symptoms, sleep impairment, activities limitation, and need for more
medication: the response options for all the questions follow a 4-point
Likert scale (range 0-3). The range of CARAT score is 0–30, 0 being the
complete absence of control: the minimal clinically important difference
(MCID) is 3.522. The Global Initiative for Asthma
(GINA) classification 201723 and ARIA
(2008)6 were used to classify asthma according to its
severity.
Statistical
analyses
Data were described as frequency (%), mean (standard deviation
[SD]), or median (interquartile range [IQR]) for categorical,
continuous, and ordinal variables, respectively. To test the association
among quality of life and control (RHINASTHMA and CARAT – total and
subdomains) scores, and AR-asthma (independent variable), we first used
a bivariate analysis using Wilcoxon rank-sum test. Then, we constructed
univariable (unadjusted) and multivariable (adjusted) regression models
among the independent variable and HRQoL and control scores using a
mixed effect Poisson regression model. As potential confounders, we
tested fixed factors (age, sex, BMI, smoking status, exposure to smoke,
education, ARIA grade, sensitivity to allergens, and drugs taken in the
last 12 months) and a random factor (the country). To include
confounders in the regression models, we used a priori evidence
criteria, i.e., covariates were considered as confounders if were found
consistent in previous literature. However, confounders were retained in
the model if they modified the estimates of the remaining variables by
more than 10%. We checked the collinearity of the confounders using the
variance inflation factor (VIF). The parsimony of the models was
confirmed by Akaike’s information criteria (AIC).
We also performed two secondary analyses. Firstly, we tested if there
was any effect modification by obesity on the association between
AR-asthma, and the HRQoL and control scores. Secondly, we performed
meta-analyses to determine if there were any heterogeneity in the HRQoL
and control (total) scores between the participating countries. All
analyses were conducted using a complete case approach in Stata V.16
(StataCorp, College Station, TX, USA), and a p-value < 0.05
was considered statistically significant.