MEDISTAR STUDY: Mediterranean Diet and Smoking in Tarragona and Reus
Phase: NA
Conditions: Lung Diseases
Sponsor: Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina



 
2 
 
RESEARCH TEAM 
Principal Investigator 
Francisco Martín Luján 
 
Co-investigators 
Rosa Solà Alberich 
Mª Victoria Arija Val 
Mar Sorli Aguilar 
Patricia Salamanca González 
Rosa Maria Valls Zamora 
Antoni Santigosa Ayala 
Roxana-Elena Catalin 
Translation and Localization 
Mª Teresa Canela Armengol 
 
Research support team (IDIAP-JG Reus-Tarragona) 
Josep Basora Gallisà 
Gemma Flores Mateo 
Cristina Rey Reñones 
 
 
 
 
 
 
 
 
 
 
 
 

 
3 
CONTENTS 
1. Summary .......................................................................................................... 4 
2. Abbreviations ................................................................................................... 5 
3. Project description ........................................................................................... 6 
3.1. Background of the topic 
3.2. Preliminary results  
3.3. Hypothesis and objectives 
3.3.1.  Hypothesis 
3.3.2.  Primary objective 
3.3.3.  Secondary objectives 
4. Methodology and work plan .......................................................................... 10 
4.1. Design 
4.2. Participants 
4.3. Calculation of the sample 
4.4. Interventions 
4.5. Data collection 
4.6. Study variables 
4.7. Statistical analysis 
5. Timeline  ......................................................................................................... 14 
6. Limitations and strengths of the study .......................................................... 16 
7. Ethical aspects ................................................................................................ 18 
8. Available instrumentation and facilities  ....................................................... 19 
9. Funding sources ............................................................................................. 19 
10. References ................................................................................................... 20 
11. Annexes and figures ..................................................................................... 22 
 

 
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1. SUMMARY 
Recent studies have shown the impact of eating patterns on lung function. However, 
the specific benefits of the Mediterranean Diet (MD) in preventing pulmonary 
dysfunction are not well known. 
 
Objective. To evaluate the effect of MD adherence on the deterioration of lung 
function in smokers. 
 
Methodology. Design: Controlled, parallel, multicenter, cluster-randomized clinical 
trial. Participants: 750 active smokers aged 25 to 75 years with a cumulative 
consumption of more than 10 packets/year, without previous respiratory disease 
and who agree to the conditions of the study and sign an informed consent to 
participate. Scope: 20 Primary Care Centers managed by the Catalan Health 
Institutes in Tarragona Province, to be randomly assigned to a control or an 
intervention group (1:1). All participants will receive advice to quit smoking. 
Intervention: A 2-year nutritional intervention designed to increase MD adherence. 
Elements include: 1) annual visit to deliver personalized nutritional education, 2) 
annual telephone contact to reinforce the intervention, and 3) access to an ad hoc 
online dietary blog. Control group: Continuation of usual diet pattern. Assessment 
(both groups, initially and annually for two years): a) pulmonary function, evaluated 
by forced spirometry and b) adherence to the MD, evaluated by a 14-item 
questionnaire and medical tests. Statistical analysis: Intention-to-treat basis, with 
the individual smoker as unit of analysis. Pulmonary function and adherence to a 
Mediterranean-style diet in both groups will be compared. 
 
Expected results. MD adherence prevents the deterioration of lung function in 
smokers without previous respiratory disease. Thus, MD is key to pulmonary disease 
prevention, together with the recommendation of smoking cessation. 

 
5 
 
2. ABBREVIATIONS 
PCC: Primary care center 
MD: Mediterranean diet 
FEV1: Expiratory flow in the first second 
FVC: Forced vital capacity 
ICS (Catalan acronym): Catalan Institute of Health 
IDIAP - Jordi Gol (Catalan acronym): Research Institute for Primary Care - Jordi Gol 
BMI: Body mass index 
COPD: Chronic obstructive pulmonary disease 
MEDISTAR: MEditerranean DIet and Smoking in Tarragona and Reus 
AbC: Abdominal circumference 
PERIS (Catalan acronym): Strategic Plan for Research and Innovation in Health 
DCQ: Data collection questionnaire 
RESET: REsults of Spirometry to Encourage Tobacco cessation 

 
6 
 
3. PROJECT DESCRIPTION  
3.1. BACKGROUND OF THE TOPIC 
Nutrition and dietary habits are recognized factors in the development, progression, 
and prevention of chronic pathologies such as cancer and cardiovascular diseases 
[1,2]. However, the impact of diet on lung function and respiratory diseases is not as 
well established [3]. 
 
In our environment, smoking is the main factor in the etiopathogenesis of 
respiratory pathology, although other factors may also be involved, such as 
environmental agents, respiratory infections, genetic disorders, and dietary habits 
[4]. Inhalation of tobacco smoke particles accelerates the physiological decline of 
lung volume attributable to aging and increases susceptibility to respiratory 
dysfunction [5]. For years, it has been known that tobacco smoke generates 
thousands of free radical particles, an important source of oxidative stress and 
inflammation.  
This effect can be neutralized by the action of enzymatic antioxidants such as 
superoxide dismutase, catalase, or glutathione peroxidase. Dietary intake of other 
antioxidants also may have a protective effect on lung function [6]. Specifically, 
evidence of the protective action of certain food and nutrients on pulmonary 
ventilation parameters such as forced vital capacity (FVC) and expiratory flow in the 
first second (FEV1) has been reported [7]. Thus, consumption of fruits and 
vegetables with a high content of antioxidant vitamins, phenolic compounds, 
minerals, and dietary fiber has a positive effect on respiratory health [8-9]. Omega-3 
fatty acids present in blue fish and shellfish have beneficial effects on the 
inflammatory mechanisms involved in the pathophysiology of chronic obstructive 
pulmonary disease (COPD) [10]. In contrast, high consumption of processed meat 
has been associated with worse pulmonary function and increased risk of COPD [11-
12]. Also, low or moderate alcohol consumption has been associated with better 
lung function, while excessive intake has detrimental effects [13-14]. 
 

 
7 
Although the evaluation of the effect of individual foods has been valuable, it 
presents conceptual and methodological limitations because the diet contains a 
variety of foods that may interact, with varying effects [15]. Therefore, analysis of 
dietary patterns is now considered to offer a better approximation to the study of 
the effects of food on health. Available evidence shows that the "western" diet with 
high consumption of fried and processed foods, processed meats, refined sugars, 
and sweets increases the risk of COPD [16-17] and that a "healthy" diet rich in whole 
grains, vegetables, fruits, and fish is associated with better lung function [18]. In this 
context, our group carried out a pioneering observational study that found a 
Mediterranean-type pattern is more likely to preserve lung function in smokers 
without previous respiratory disease, compared to a western diet, and a pattern of 
alcohol use was associated with an increased probability of functional impairment 
[19-21]. Therefore, adherence to a healthy dietary pattern, in addition to smoking 
cessation, offers new perspectives on avoiding the preventable loss of lung function 
in smokers. 
 
The traditional dietary pattern of Mediterranean countries includes a set of 
characteristic foods with beneficial effects on inflammation and oxidation, such as 
legumes, fresh fruits and vegetables, blue fish, olive oil and nuts. The MD is rich in 
antioxidants (vitamin C and E, beta-carotene and folates), phenolic compounds (the 
most abundant being flavonoids), and monosaturated and polyunsaturated fatty 
acids [22]. This pattern has been associated with the reduction of cardiovascular 
events and all-cause mortality, and for years has been recommended in 
cardiovascular prevention. Extending this recommendation to respiratory pathology 
related to smoking is of evident interest in primary prevention. 
 
To our knowledge, no national or international groups are currently working on the 
protective effects of MD in preventing respiratory diseases. Therefore, a clinical trial 
is presented with the objective of evaluating the impact on lung function of an 
intervention to increase MD adherence in a cohort of smokers without previous 
respiratory pathology. 
 

 
8 

 
9 
 
3.2. PRELIMINARY RESULTS  
The present study is part of a broader program to reduce smoking behaviors 
developed by the Study Group on Respiratory Pathology in Tarragona, accredited by 
IDIAP Jordi Gol (the Catalan acronym for the Jordi Gol Institute for Primary Care 
Research). The RESET study is a clinical trial on smoking cessation, designed to 
evaluate the efficacy of a motivational intervention based on information obtained 
from spirometry (Project FIS PI 11/01962) [19]. Within the RESET study, a two-phase 
project was designed. In the first phase, the RESET-DIET observational study, 
researchers identified the main dietary patterns present in the smoking population 
attended at primary care centers (PCCs) in Catalonia, and examined their association 
with lung function. Their results are already in an advanced stage of publication [20-
21]. 
 
The RESET-DIET study identified three main dietary patterns: alcohol consumption 
(wine, beer and distillates), a westernized pattern (red and processed meat, dairy 
products and sugary drinks) and a Mediterranean pattern (poultry, eggs, fish, 
vegetables, legumes, potatoes, fruit and nuts). Multivariate analysis associated 
changes in respiratory function with the alcohol consumption pattern in both men 
and women (OR 4.56, 95% CI 1.58-13.18) and with the westernized pattern only in 
women (OR 5.62, 95% CI 1.17-27.02). In contrast, the Mediterranean pattern 
trended toward an inverse association with functional deterioration, without 
reaching statistical significance (OR 0.71, 95% CI 0.28-1.79) [20]. It was also observed 
that the inverse relationship with lung function is influenced by personal 
characteristics, such as abdominal obesity, especially in men [21]. 
 
These findings suggest that certain personal characteristics and dietary patterns in 
the smoking population are associated with impaired lung function. In addition to 
recommending smoking cessation, health professionals should consider an 
intervention regarding dietary factors. This is precisely the basis for the second-
phase project, the MEDISTAR study (Mediterranean Diet and Smoking in Tarragona 
and Reus), detailed in the following section. 

 
10
 
3.3. HYPOTHESIS AND OBJECTIVES 
3.3.1. Hypothesis 
Increased adherence to the MD pattern in addition to smoking cessation advice, will 
prevent the impairment of lung function in smokers without respiratory disease. 
 
3.3.2. Primary objective 
To evaluate the effect of MD adherence on the deterioration of lung function in 
smokers without previous respiratory disease treated in Tarragona PCCs. 
 
3.3.3 Secondary objectives  
In smokers without previous respiratory disease: 
1) To evaluate the effectiveness of a multicomponent nutritional educational 
intervention designed to increase adherence to the MD pattern. 
2) To study the relationship between lung function and anthropometric 
parameters such as the abdominal circumference (AbC) and body mass index 
(BMI). 
3) To study the relationship between lung function and various markers of 
food consumption, inflammation and oxidation.  

 
11
 
4. METHODOLOGY AND WORK PLAN 
4.1. DESIGN 
A multicenter, cluster-randomized, controlled clinical trial aimed at assessing the 
effect on lung function of increasing MD adherence in a cohort of smokers without 
previous respiratory pathology. (Clinical Trial registry with Nº 000). 
Figure 1 shows the flow diagram of the project. 
 
4.2. PARTICIPANTS 
The study population will be recruited from patients treated at 20 PCCs managed by 
the Catalan Institute of Health (ICS) in Tarragona, which provide assistance to an 
adult population of approximately 280,000 inhabitants. 
 
Participants who give written informed consent to participate and meet the 
following criteria will be included: 
- Active smoker with Đuŵulative ĐoŶsuŵptioŶ ≥ϭϬ paĐk-years 
- Age between 25 and 75 years, inclusive 
- Internet access 
Participants with any of the following criteria will be excluded: 
- History of respiratory disease 
- Chronic or terminal disorder that affects basal parameters 
- Any limitation to follow-up participation 
 
4.3. CALCULATION OF THE SAMPLE 
The sample size was initially calculated for a simple randomized design, using the 
ARC“INU“ approǆiŵatioŶ. Thus, iŶ a ďilateral ĐoŶtrast, aĐĐeptiŶg a risk α = Ϭ.Ϭ5, a 
risk β <Ϭ.Ϯ and a follow-up loss rate of 25%, 192 subjects are required in each group 
to detect significant differences between two proportions, estimating that this 
would be 0.17 in group-1 and 0.31 in group-2 [20]. Accepting that the effect of the 
design is 1.7, applying an intraconglomerate correlation coefficient <0.05 [23], a 
sample of 750 participants will be needed, 375 in each group (38 volunteers from 
each participating PCC). 

 
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4.4. INTERVENTIONS 
Participating centers will be assigned randomly to a control or intervention group 
(1:1). Volunteers will be referred to an initial visit (V0) to confirm inclusion criteria 
and sign an informed consent (Annex 1). Basal variables will be collected at that 
time. 
 
Participants from the intervention PCCs will enter into an educational program to 
increase adherence to the MD. It will consist of five contacts that integrate three 
operational components: 
 
a) Explain the details of the MD and the benefits of following this dietary 
pattern in an individual visit of 25-30 minutes (V1). Data on the study 
variables will be collected and medical tests will be performed. This data 
gathering will be repeated annually for two years (V3 and V5). 
 
b) Clarify any doubts about following the MD pattern and other advice 
received, in a telephone conversation. This annual contact will reinforce the 
intervention (V2 and V4). 
 
c) Provide information about MD foods, cooking tips, adapted recipes, and 
other related topics in an ad hoc nutrition blog. 
 
The control group will carry out the same 5 visits (3 individual visits and 2 phone 
calls), although no changes will be made in their usual diet and they will not be 
provided with access to the nutritional blog. 
 
All participants will receive health advice to stop smoking, according to the protocol 
recommended to health professionals in Catalonia: a proposal of smoking cessation 
expressed in a clear, firm, and personalized way, in an empathic and respectful 
setting. 

 
13
At the end of the study, if the intervention is effective, control group members will 
be invited to participate in the same intervention program. 
 
 
4.5. DATA COLLECTION 
All the information will be collected in a computerized data collection questionnaire 
(DCQ), only accessible from the administrators of the ICS corporate Intranet in 
Tarragona. Access will be restricted and controlled by a personal password for each 
researcher, who will be responsible for entering participant data. 
 
This DCQ will include initial information (V0): 
- 
Socio-demographic data (age, sex, marital status, number of children, level of 
education, social class) 
- 
Medical history and respiratory symptomatology (dyspnea, cough, 
expectoration, chest pain, other symptoms) 
 
At follow-up visits (V1, V2 and V3), the following information will be obtained: 
- 
Physical examination (weight, height, BMI, blood pressure, and level of 
exhaled carbon monoxide determined by CO-oximetry) 
- 
Smoking habit (accumulated consumption, current consumption, nicotine 
dependence, motivation to quit smoking) 
- 
Alcohol consumption 
- 
Physical Activity Classification Questionnaire [24] 
- 
Food frequency questionnaire to assess food consumption [25] 
- 
MD adherence, based on 14-item questionnaire [26] 
- 
12-lead electrocardiogram 
- 
Forced spirometry and bronchodilator test to measure FVC, FEV and the ratio 
between them (FEV1/FVC). 
- 
Levels of glucose, total cholesterol and fractions, triglycerides, creatinine and 
transaminases (serum, autoanalyzer) 

 
14
- 
Serum inflammation markers: high-sensitivity C-reactive protein and 
interleukin-6 (serum, autoanalyzer and assay ELISA) 
- 
Oxidation markers: oxidized LDL in plasma (plasma EDTA, assay ELISA)  
- 
Food consumption markers: excreted of total polyphenols (fresh urine, Folin-
Ciocaletau)  
 
4.6. STUDY VARIABLES  
A) The main variable of interest is impaired lung function at the end of follow-up, 
defined as at least one of the following values: FVC <80%, FEV1 <80%, and FEV1/FVC 
<0.7 [27]. As secondary variables, spirometry tests (FVC and FEV1), anthropometrics 
(BMI and AbC), and dietary patterns (adherence and diameter consumption 
markers) will be evaluated at the end of follow-up. 
 
4.7. STATISTICAL ANALYSIS 
Data will be extracted from the centralized database for blinded analysis, based on 
intention to treat. The efficacy of randomization will be assessed by comparability 
and homogeneity of the intervention and control groups. Losses to follow-up will be 
calculated for each group and evaluated to determine whether the proportion of 
losses is independent of assignment to the intervention or control group. 
 
Qualitative variables will be described as frequencies or percentages, and 
quantitative variables by the mean and standard deviation or interquartile range. 
Analysis will be stratified by study groups and compared at basal level usiŶg the χϮ 
test for qualitative and the Student t or Mann-Whitney U test for quantitative 
variables. 
 
Pulmonary function, anthropometric data, foods consumed, and MD adherence at 
V1 will be compared to values obtained at the final visit (V5). A multivariate analysis 
will be performed to determine the factors independently associated with the 
observed changes, adjusting for relevant covariates. The results will be presented as 

 
15
hazard ratios, with 95% confidence intervals. All analysis will be performed with the 
SPSS v22.0 program, considering a p-value <0.05 statistically significant. 

 
16
 
5. TIME LINE 
Phases of project development, with activities and tasks to be developed by the 
entire research team: 
 
Preparation phase 
Activity 1- Registration and publication of study protocol 
Activity 2- Design of questionnaires and nutrition education material 
Activity 3- Design and development of the nutritional blog 
Activity 4- Presentation of the project to PCCs 
Activity 5- Training of Associate Researchers (PCC health professionals) 
 
Implementation and follow-up phase 
Activity 7- Recruitment of patients. Beginning of the intervention 
Activity 8- Data collection, introduction to DCQ 
Activity 9- Conduct follow-up visits (in person and by telephone) 
 
Data analysis and final evaluation 
Activity 10- Periodic quality analysis of records 
Activity 11- Statistical analysis. Communication and publication of 
intermediate results 
Activity 12- Statistical analysis. Communication and publication of final 
results 
 
The schedule of tasks and data collection at each visit during the implementation 
and follow-up phase is detailed below. 

 
17
 
 
 
 
 
 
 
 
 
 
Visit 0 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Study timeline 
- 30 days 
Day 0 
6 months 
12 months 
18 months 
24 months 
Aims 
Randomization 
Selection 
Inclusion 
Data 
collection  
Intervention 
Phone  
follow-up 
Reinforcement 
Data 
collection 
Intervention 
Phone  
follow-up 
Reinforcement 
Data 
collection  
Procedures 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
Online data collection 
(DCQ) 
X 
X 
X 
X 
X 
X 
Basic physical 
examination 
 
X 
 
X 
 
X 
Laboratory tests 
 
X 
 
 
 
 
Food questionnaires 
and dietary 
information 
 
X 
 
X 
 
X 
Forced spirometry  
 
X 
 
X 
 
X 
Inflammation / 
oxidation markers  
 
X 
 
X 
 
X 
Intervention 
 
 
 
 
 
 
Control group: usual 
diet, usual clinical 
consultations, 
telephone follow-up 
 
X 
X 
X 
X 
 
Intervention Group: 
MD Nutrition Program 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
 

 
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6. LIMITATIONS AND STRENGTHS OF THE STUDY 
The present study has several limitations. The most important is related to the study 
population, because inclusion criteria may limit successful recruitment. 
 
The intervention may be less intensive than that described in cardiovascular 
prevention studies [28]. However, it is an innovative strategy in the prevention of 
respiratory pathology and its pragmatic design take into account the actual working 
conditions in daily clinical practice in primary health care. It focuses on reinforcing 
the consumption of foods considered as protective in the typical diet of the 
Mediterranean region and reducing the consumption of foods in the standard 
Western diet that have harmful effects on pulmonary physiology. If the efficacy of 
this intervention can be demonstrated, it could be readily implemented in clinical 
practice.  
 
Another limitation to take into account is the knowledge about dietetics and 
nutrition and the skills of the collaborating health professionals. Knowledge and skills 
are essential to properly evaluate MD adherence in terms of specific foods, as well 
as to increase the validity and reliability of the information collected using the study 
questionnaires and nutritional education. Therefore, in order to standardize the 
intervention, the dieticians who collaborate in the MEDISTAR study and who design 
the intervention and develop the educational content and materials will provide 
thorough training in MD and pulmonary function at the beginning of the study for all 
participating health professionals.  
 
The effect on lung function will be evaluated by comparing the results of three 
consecutive forced spirometry measurements, taken annually during the three-year 
project period. Although this should be sufficient time to allow observations about 
the longitudinal effect of the diet on spirometry values, it could be too short to show 
statistically and clinically significant differences between the two study groups. In 
any case, these results should provide additional evidence of the effect of a MD on 
lung function in a population of smokers with no previous respiratory disease.  
 

 
19
A common limitation of long-term projects is the loss of participants during the 
follow-up. To minimize losses, a multicomponent intervention involving technology 
has been designed. The use of a nutritional blog is intended to facilitate interaction 
between participants in the intervention group and the researchers, beyond the 
scope of the office visit, and should favor adherence during the study period. 
Moreover, annual telephone contacts should help to consolidate the intervention 
and maintain direct personal contact with all participants in both study groups. 
 
The MEDISTAR study also has important strengths. It takes a multidisciplinary 
approach to the serious health problem caused by tobacco use, integrating elements 
of epidemiological, clinical, and basic research. In addition, the research team 
includes professionals with complementary experience in conducting clinical trials of 
lifestyle interventions. The intervention is carefully structured to determine its effect 
on the main clinical outcomes and maximize its transferability to the primary health 
care setting. 
 
This highly innovative project offers a new paradigm of nutritional recommendations 
to address pulmonary dysfunction in smokers. This approach, drawing on a field of 
nutrition that has scarcely been studied and online new technology that is already 
familiar to much of the study population, may contribute to better adherence to the 
intervention. 

 
20
 
 
7. ETHICAL ASPECTS 
The study will follow the principles set out in the Declaration of Helsinki and the 
guidelines of Good Clinical Practice of the International Conference on 
Harmonization (ICH GCP). It also fulfills the requirements established in the 
legislative framework in Spain for the field of biomedical research, the protection of 
personal data and bioethics, as well as the published guidelines of good clinical 
practice. 
 
The protocol has been evaluated by the Ethics Committee of IDIAP - Jordi Gol, 
incorporating its recommendations and suggestions. 
 
During recruitment, all individuals will receive information about the study 
objectives and the activities related to their participation, and will sign an informed 
consent prior to their inclusion (Annex 1). 
 

 
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8. AVAILABLE INSTRUMENTATION AND FACILITIES  
The research team has the institutional support of the ICS Directorate of Primary 
Care for Tarragona Province. During the project period, researchers will have the use 
of facilities belonging to ICS primary care centers in the cities of Tarragona and Reus 
and will have the technical resources at their disposal need for the study, including 
the blog and follow-up telephone calls. All the centers participating in the study 
function as primary care teams, with a common electronic medical registry system 
(e-CAP) managed by ICS. All PCCs have the physical space necessary for the 
laboratory tests to be carried out, in a confidential environment for the patients. 
 
This project will also count on the collaboration of staff assigned to the Research 
Support Unit of the ICS Primary Care Area of Tarragona-Reus, which has the 
computing resources required to manage the data generated by the study. The 
economic and administrative management of the project will rely on the 
infrastructure of IDIAP - Jordi Gol, which includes the Study Group on Pathology of 
the Respiratory System. In addition, the Primary Care Area of Tarragona-Reus, 
through its research coordinator, is a member of the board of the Pere Virgili 
University Institute Board (Rovira i Virgili University, Tarragona), which provides 
access to the methodological and technical resources of these institutions. 
 
 
9. FUNDING SOURCES 
This project fits within the Strategic Plan for Research and Innovation in Health 
(Catalan acronym, PERIS) for 2017-2019, with funding granted by the Department of 
Health of the Government of Catalonia. 

 
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Shaheen SO et al. The relationship of dietary patterns with adult lung function 
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Martin F et al. Multicentric randomized clinical trial to evaluate the long-term 
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Sorli M et al. Dietary patterns are associated with lung function among Spanish 
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Campbell M et al. Sample size calculations for cluster randomised trials. 
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VallďoŶa Cl et al.  ͞Guia de presĐripĐió d’eǆerĐiĐi físiĐ per a la salut͟ ;PEF“Ϳ, 
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11. ANNEXES AND FIGURES 
 
Annex 1. Informed Consent. 
 
 
INFORMATION SHEET FOR PARTICIPANTS  
(TRANSLATION) 
 
MEDISTAR clinical trial (Mediterranean Diet and Smoking in Tarragona and Reus). 
Effect of the Mediterranean Diet on lung function in smokers without previous 
respiratory pathology. 
 
Principal investigator 
Francisco Martín Luján.  
Directorate of Tarragona-Reus Primary Care Area, Catalan Institute of Health. 
 
Objective 
To evaluate the effect of Mediterranean Diet on the deterioration of lung function in 
smokers without respiratory disease. 
 
Methodology and study development 
A total of 20 primary care centers in Tarragona are participating in this study. The 
intention is to include a total of 750 active smoking individuals who meet the 
inclusion criteria and agree to participate voluntarily. Once included in the study, 
participants will be divided into two groups (control group and intervention group). 
One group will continue to follow their usual diet; the intervention group will be 
asked to follow the Mediterranean Diet. 
 
Intervention 
All people will be interviewed at the beginning of the study and on several follow-up 
visits during two years. Researchers will collect information about their dietary 
habits and provide nutritional information. We will evaluate and compare how lung 

 
26
function changes in both groups. At the end of the study, if the intervention is 
effective, control group members will be invited to participate in the same 
intervention program. 
 
Analysis of biological markers 
In order to compare dietary adherence, in addition to the questionnaires, several 
͞ďiomarkers͟ will be tested as a direct measure of food consumption. Therefore, this 
consent form includes the authorization to obtain blood and urine samples, which 
will be used to analyze these biological markers (such as oleic acid, resveratrol, and 
hydroxytyrosol), which indicate a response to a nutritional intervention. We will also 
analyze some markers of inflammation and oxidation that may be related to the diet. 
 
The use and storage of the samples for the study has been approved by the 
Committee for Ethics and Clinical Research of the Institute for Research in Primary 
Care (IDIAP) Jordi Gol. 
 
Can I see the results of the biological markers tests? 
You have the right to the data obtained from your sample if you request it. In any 
case, if a test result is relevant to your health, you will be informed through your 
primary care physician. 
 
Adverse Events 
No adverse effects are anticipated. Any health problem that occurs during the study 
period will be attended according to the usual clinical practice in your Primary Care 
Center. Study participation will be suspended if any other health priority affects your 
involvement. 
 
Voluntary participation 
Your participation in this study is completely voluntary and you can withdraw from it 
at any time, without having to give any explanation and without this affecting your 
medical care or your relationship with your usual health care team. 
 

 
27
Confidentiality 
All your personal and biological data will be considered confidential and treated with 
the level of protection (RD 1720/2007) required for this type of data according to the 
Organic Law of Protection of Personal Data (15 /1999). 
 
The samples obtained and their data will be protected with a code. The key to the 
codes will be in sole custody of the principal investigator of the study, who 
guarantees absolute confidentiality. 
 
The results of the study may be communicated to the scientific community in the 
context of seminars or conferences, or published in scientific articles. However, the 
identity of the participants will not be revealed in any publication or report related 
to this study. 
 
Additional Information 
If you have questions about any aspect of the study or you would like to discuss any 
additional questions, you can contact the dietitian, Patricia Salamanca, at 977 778 
518 or by sending an email to medistar.tgn.ics@gentcat.cat. Having read this 
information and clarified possible doubts, if you decide to participate, you must sign 
the following informed consent. 
 

 
28
 
INFORMED CONSENT SHEET 
MEDISTAR (Mediterranean Diet and Smoking in Tarragona and Reus) 
Effect of the Mediterranean Diet on lung function in smokers without previous 
respiratory pathology. 
 
Principal investigator 
Francisco Martín Luján.  
Directorate of Tarragona-Reus Primary Care Area, Catalan Institute of Health. 
 
Mr. / Mrs. (Name and surname of the participant): 
____________________________________________________________________ 
I declare that: 
• I have ďeeŶ iŶforŵed ďǇ ;Ŷaŵe aŶd surŶaŵe of the researcher): 
_____________________________________________________________________ 
 
I confirm the following: 
• I haǀe ƌead the iŶfoƌŵatioŶ sheet that has beeŶ giǀeŶ to ŵe. 
• I haǀe beeŶ able to ask ƋuestioŶs about the study. 
• My ƋuestioŶs haǀe beeŶ aŶsǁeƌed. 
• I have ďeeŶ sufficiently informed, I understand that my participation is 
voluntary, and I understand that I can withdraw from the study at any time, 
without having to give any explanation and without affecting my medical 
care. 
With respect to analysis of biochemical markers: 
• I agƌee to paƌticipate voluntarily in the analysis of biological markers by 
the MEDIS·TAR study. 
Therefore, I freely agree and sign my consent to participate in the MEDIS·TAR study. 
 
Signature (Participant): 
 
In (location) __________________, as of date: ____ / ____ / ______ 

 
29
 
Figure 1. Project flowchart: participant selection, randomization and follow-up. 
 
Visit 0 (pre-selection and inclusion of patients) 
Obtain signed informed consent for the study.  
Randomize participants by clusters (PCCs) 
CONTROL Group 
Usual diet 
Anti smoking advice 
(10 centers) 
   Visit 1 (baseline) 
Data collection 
Nutrition intervention 
Visit 3 (12 months) 
Data collection 
Nutrition intervention 
Visit 5 (24 months) 
Data collection 
Visit 2 (6 months) 
Telephone call to 
reinforce message 
Exclusion of patients who do 
not wish to participate or do 
not meet the inclusion criteria. 
MEDISTaR Study 
Smokers from 25 to 75 years old / 20 PCCs in Tarragona Province 
Visit 4 (18 months) 
Telephone call to 
reinforce message 
Visit 1 (baseline)  
Data collection 
Visit 3 (12 months) 
Data collection 
Visit 5 (24 months) 
Data collection 
ANALYSIS OF DATA 
REPORTING 
INTERVENTION Group 
Mediterranean diet 
Anti smoking advice 
(10 centers) 
Access to a nutritional blog, ad hoc