Non-Interventional, Descriptive, Cross-sectional and Unicentric Study to Describe the Clinical Management in Asthmatic Patients Attended in the Influential Area of Hospital Universitario Virgen de la Victoria, Málaga
Conditions: Asthma
Sponsor: Hospital Universitario Virgen de la Victoria

Protocol V.1.0 – 1st of December 2019 
 
             
 
 
 
NCT06811155 STUDY PROTOCOL 
 
 
PROTOCOL CODE 
 
FULL TITLE 
Non-Interventional, descriptive, cross-sectional and unicentric 
study to describe the clinical management in asthmatic 
patients attended in the influential area of Hospital 
Universitario Virgen de la Victoria, Málaga 
ABBREVIATED TITLE 
 
FINAL PROTOCOL APPROVED 
  
SPONSORSHIP 
Hospital Universitario Virgen de la Victoria, Málaga. 
CONTRIBUTING AUTHORS 
 
 
 
 
REVISION CHRONOLOGY:   
 
 
Version Date   
Document Type 
Change(s) since last version 
v1.0 – 1st of December 2019 
Original 
n/a 
 
 
 
 
 
 
 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
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PROTOCOL SYNOPSIS  
 
Protocol Code 
 
Abbreviated Title  
 
Rationale 
Asthma is a heterogenic chronic disease that affects more than 300 million 
people worldwide, which it’s characterized by acute symptomatic episodes of 
varying severity, including intermittently inflammation and narrowing of the 
airways in the lungs.  
The prevalence in Spain it is estimated to be around 5%, according to the 
European Community Respiratory Survey (ECRHS) and seems to be increased due 
to a higher rate of asthma diagnosis1. 
 
In this condition there’s substantial proportion of patients with a poor disease 
control, which conducts to an important negative impact in their health-related 
quality of life (HRQoL) and the need to use health care resources3,4.  
During the past decades multiple clinical practice guidelines, such as the 
international Global Initiative for Asthma (GINA) and national guidelines as Guía 
Española para el Manejo del Asma (GEMA) have been launched with the aim of 
improving quality of care in patients with asthma and reduce the high public 
burden associated to this disease. However, several studies have concluded that 
high proportion of patients remain uncontrolled10, being in Spain estimated 
around 50%12, and there’s direct evidence of poor adherence to the guideline’s 
recommendations for asthma management3. In terms of costs, it’s estimated that 
around 70% of total disease cost is determined to this poor control and 
management14. An adequately disease management according to guideline’s 
recommendations would result in a better disease control and a reduction of 
associated costs15, 16, 17. 
  
Objectives  
(Primary, Secondary)  
Primary objective: 
1. Describe the clinical management in asthmatic patients in the influential 
area of Hospital Universitario Virgen de la Victoria according to the 
assistance quality indicators established by GEMA guidelines (Appendix 1), 
which are the following:  
• Diagnostic confirmation by spirometry with test bronchodilator. The 
diagnostic confirmation of the patients with asthma is done with 
spirometry and bronchodilator test as an objective measure of 
functional impairment. 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
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• Sensitization study in allergic asthma. To patients with suspicion of 
allergic asthma should be performed a study of possible sensitization to 
different allergens. 
• Smoking cessation. It is recommended smoking cessation to smokers 
with asthma. 
• Educational plan in patients with asthma. Patients with asthma must 
follow a basic education program (formed by: knowledge about their 
illness, about their treatment, action plan and inhalation technique, 
documented in writing) as part of their treatment. 
• Treatment of choice in persistent asthma. The treatment of choice in 
persistent asthma includes inhaled glucocorticoid (IGC) used daily. In 
some justified cases, alternative treatment with leukotriene receptor 
antagonists can be considered. 
• Asthma treatment in pregnant women. In asthma maintenance 
treatment in pregnant woman is recommended to keep the commonly 
used drugs (agonists β2-adrenergic and inhaled glucocorticoids). 
• Periodic follow-up of patients. Necessity to make periodic monitoring 
of patients, even if they have not suffered exacerbations, through 
scheduled medical visits. 
• Periodic record of exacerbations. The specific assessment of 
exacerbations is evaluated periodically. 
 
 
Secondary objectives: 
1. To describe the sociodemographic and clinical characteristics of the 
study population. 
2. To describe the treatment patterns (maintenance treatment, reliever 
treatment, type of treatment) during the last year. 
3. To describe the disease control level in the study population. 
4. To describe the use of resources (emergency visit, Primary care visits, 
specialist visits) during the last year. 
5. To describe the number of patients with discontinuation of SABA within 
the last year and the potential impact on disease control level and use of 
resources. 
For descriptive purposes, an analysis of the objectives will be made based on the 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
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level of disease control. 
Study Design 
Cross-sectional cohort, non-interventional, descriptive and unicentric 
 
Study Population and 
Sampling Methods  
It is planned that a total of 300 patients with asthma will be included in the study.  
- 
Target enrollment/ sample size: 300 patients approximately. 
- 
Anticipated rate of enrollment: 6 months. 
- 
Estimated study start date: September 
- 
Estimated study completion date: March 
Data Source  
Patient’s electronical medical chart 
Data Analysis Methods 
Data analysis will be performed using SAS Enterprise Guide Version 7.1 and a 
statistical analysis plan will be designed and agreed before the data analysis 
initiation. 
All the analyzes will be performed by descriptive statistical methods of all the 
variables separately. 
The quantitative data will be described by the following statistical parameters: 
number of valid patients (N valid), number of missing data (N missing), mean, SD, 
median, minimum, maximum and according to the distribution of the analyzed 
variable, quartiles will also be presented (percentiles 25 and 75). 
The qualitative data will be presented through the length-frequency distributions 
(absolute and relative). For both cases, the following will be specified: number of 
observations (N) and number of missing data (N missing). 
Sample Size and Power 
In order to estimate a proportion of 50% (maximum variability), with a margin of 
error of +/- 6 percentage points and a confidence level of 95%, a sample size 267 
patients will be required. Assuming 10% of patients with non-available data from 
the medical records, total sample size must be 300 patients.  
The study sample size must allow the estimation of dichotomic variables and to 
determine the percentage of compliance of each quality care indicator 
established by the GEMA guidelines. This percentage will allow to establish the 
degree of compliance of each group of indicators in the site. 
Limitations 
Cross-sectional study, missing data in clinical records 
 
 
 
 

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TABLE OF CONTENTS 
 
1. INTRODUCTION / BACKGROUND 
 
 
 
 
 
 
  8 
2. OBJECTIVES 
 
 
 
 
 
 
 
 
 
10 
2.1. Primary 
 
 
 
 
 
 
 
 
 
10 
2.2. Secondary 
 
 
 
 
 
 
 
 
10 
 
3. RESEARCH METHODOLOGY  
 
 
 
 
 
 
11 
3.1. Study Design 
 
 
 
 
 
 
 
 
11 
3.2. Study Population  
 
 
 
 
 
 
 
12 
 
3.2.1. Eligibility criteria 
 
 
 
 
 
 
12 
 
3.2.1.1. Inclusion criteria 
 
 
 
 
 
 
13 
 
3.2.1.2. Exclusion criteria 
 
 
 
 
 
 
13 
 
 
 
3.2.2. Sampling 
 
 
 
 
 
 
 
13 
3.3. Data Source / Data Collection 
 
 
 
 
 
 
13 
 
3.3.1. Endpoints 
 
 
 
 
 
 
 
14 
 
3.3.1.1. Primary endpoint 
 
 
 
 
 
 
14 
 
3.3.1.2. Secondary endpoints  
 
 
 
 
 
14 
 
3.4. Sample Size / Power Calculations 
 
 
 
 
 
17 
3.5. Hypotheses 
 
 
 
 
 
 
 
 
18 
 
4. DATA ANALYSIS CONSIDERATIONS 
 
 
 
 
 
 
18 
5. LIMITATIONS  
 
 
 
 
 
 
 
 
21 
6. STUDY CONDUCT, MANAGEMENT AND ETHICS 
 
 
 
 
21 
6.1. Ethics Committee / IRB Approval 
 
 
 
 
 
21 
6.2. Informed Consent 
 
 
 
 
 
 
 
22 
6.3. Data Protection  
 
 
 
 
 
 
 
22 
6.4. Personally Identifiable Information (PII)  
 
 
 
 
23 
6.5. Adverse Event (AE), Pregnancy Exposure and Incident Reporting 
 
24 
 
6.5.1. Definitions of adverse events  
 
 
 
 
25 
 
7. EXTERNAL INVOLVEMENT 
 
 
 
 
 
 
 
25 
7.1. Third Party Supplier 
 
 
 
 
 
 
 
25 
7.2. External Expert / Health Care Professionals 
 
 
 
 
25 
 
Appendix 1: Quality assistance indicators – GEMA Guidelines  
 
 
 
26 
Appendix 2: Asthma Control Test (ACT) - Prueba de Control de Asma (Spanish) 
 
27 
Appendix 3: Patient Information Sheet and Informed Consent Form 
 
 
28 
Appendix 4: Research team 
 
BIBLIOGRAPHY 
 
 
 
 
 
 
 
 
 
32 

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ABBREVIATIONS 
 
ACT 
Asthma Control Test 
BMI 
Body Mass Index 
DMP 
Data Management Plan 
ED 
Emergency Department 
ECRHS 
European Community Respiratory Survey 
eCRF 
Electronic Case Report Form 
GCP 
Good Clinial Practice 
GDPR 
General Data Protection Regulation 
GEMA 
Guía Española para el Manejo del Asma 
GINA 
Global Initiative for Astma 
HRQoL 
Health-Related Quality of Life 
IC 
Informed Consent 
ICH 
International Conference on Harmonisation 
IEC 
International Ethics Committee 
IGC 
Inhaled glucocorticoid 
IRB 
International Review Board 
OCS 
Oral Corticoids 
PBD 
Post Bronchodilator 
SAP 
Statistical Analysis Plan 
 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
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1. INTRODUCTION/BACKGROUND  
 
Asthma is a heterogenic chronic disease characterized by acute symptomatic episodes of 
varying severity, including intermittently inflammation and narrowing of the airways in the 
lungs. The prevalence of this disease is high as affects more than 300 million people worldwide, 
which varies by country. In Spain, the prevalence it is estimated to be around 5%, ranged 
between 1% in Huelva and 4,7% in Albacete, according with the European Community 
Respiratory Survey (ECRHS), and seems to be increased due to a higher rate of asthma 
diagnosis1. 
 
It’s important to note that in this condition there is a substantial proportion of patients with 
inadequate control of their disease, which conducts to a higher morbidity and mortality2. The 
poor disease control is associated to an important negative impact in patient’s health-related 
quality of life (HRQoL), causing them daily activity impairment, loss of work productivity and the 
need of using unscheduled doctor visits and hospital services3, 4. The direct and indirect costs in 
patients with a poor disease control represents an important proportion of the total cost of 
asthma, which it's estimated to be around 1-2% of the total public healthcare resources in 
developed countries, especially in patients with severe-persistent asthma4, 5. 
 
The facts previously exposed turns this disease into a major public health problem due to its 
high prevalence within all age and sex groups and the high proportion of uncontrolled patients, 
which causes a high health burden to the National Health System, and which affects directly on 
the affected patients, as well as their families and the society6. 
 
For this reason, during the past decades multiple clinical practice guidelines have been 
designed to improve the quality of care in patients with asthma and to reduce the high public 
burden associated to this disease7. International guidelines such as the Global Initiative for 
Asthma (GINA) and national guidelines as Guía Española para el Manejo del Asma (GEMA) in 
Spain, both of them stating that a good disease control can be achieved by most of asthma 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
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patients, were launched to increase the technical training of health professionals in order to 
reach a better disease management and conduct to a better quality of life in these patients 8, 9.  
 
Specifically, GEMA guidelines also includes a tool to assess the level of assistance quality care 
through 8 indicators covering 4 dimensions: diagnose, non-pharmacological treatment, 
pharmacological treatment, monitoring. 
 
However, since guidelines have been launched, there’s still evidence of high proportion of 
patients with poorly disease control and large impact in patient’s health-related quality of life10. 
Despite the availability of therapeutic recommendations through guidelines, clinical studies 
have shown that there’s poor adherence to guidelines goals3. The Asthma Insight and Reality 
surveys, which were performed in several regions worldwide, concluded that all participating 
countries didn’t met GINA goals. Specifically, in Central and Eastern Europe, the results showed 
a high proportion of asthma population who described physical activity limitations (68,2%) and 
acute symptoms during the previous 4 weeks (74%). Regarding disease monitoring, it’ 
important to note that the results demonstrated that a 36,2% of asthmatic patients had never 
performed a lung function test11. A recent study conducted in Spain and Italy also evidenced a 
generally poor disease control, with around 50% of participant patients being considered 
uncontrolled12, and that strategies were needed to improve the management of this disease as 
it was concluded in a study performed in Spain to assess the disease control according to GINA 
criteria13. 
 
In terms of costs, it’s estimated that around 70% of the total cost of the disease is determined 
by this poor control and management14. An adequately disease management based in a higher 
use of preventive anti-inflammatory medication, a better education in asthma patients and an 
accurately follow of the recommendations of guidelines would result in a greater disease 
control and in a reduction of associated costs15, 16, 17. 
 
This evidence raises the need to determine the assistance quality care in asthma population in 
the influential area of Hospital Universitario Virgen de la Victoria through the assistance quality 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
9 
 
care indicators established by GEMA guidelines. The aim of this study is to obtain clinical data 
that allow to assess assistance quality degree in order to find improvement opportunities to 
achieve a better control of asthmatic patients within this influential area.  
2. OBJECTIVES  
2.1. 
Primary objective: 
- 
To describe the clinical management in asthmatic patients in the influential area of 
Hospital Universitario Virgen de la Victoria according to the assistant quality indicators 
established by GEMA guidelines (Appendix 1), which are the following: 
o Diagnostic confirmation by spirometry with test bronchodilator. The diagnostic 
confirmation of the patients with asthma is done with spirometry and 
bronchodilator test as an objective measure of functional impairment. 
o Sensitization study in allergic asthma. To patients with suspicion of allergic 
asthma should be performed a study of possible sensitization to different 
allergens. 
o Smoking cessation. It is recommended smoking cessation to smokers with 
asthma. 
o Educational plan in patients with asthma. Patients with asthma must follow a 
basic education program (formed by: knowledge about their illness, about their 
treatment, action plan and inhalation technique, documented in writing) as part 
of their treatment. 
o Treatment of choice in persistent asthma. The treatment of choice in persistent 
asthma includes inhaled glucocorticoid (IGC) used daily. In some justified cases, 
alternative treatment with leukotriene receptor antagonists can be considered. 
o Asthma treatment in pregnant women. In asthma maintenance treatment in 
pregnant woman is recommended to keep the commonly used drugs (agonists 
β2-adrenergic and inhaled glucocorticoids). 
o Periodic follow-up of patients. Necessity to make periodic monitoring of 
patients, even if they have not suffered exacerbations, through scheduled 
medical visits. 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
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o Periodic record of exacerbations. The specific assessment of exacerbations is 
evaluated periodically. 
 
2.2. 
Secondary objectives: 
 
- 
To describe the sociodemographic and clinical characteristics of the study population. 
- 
To describe the treatment patterns (maintenance treatment, reliever treatment, type of 
treatment) during the last year. 
- 
To describe the disease control level in the study population. 
- 
To describe the use of resources (emergency visit, Primary care visits, specialist visits) 
during the last year. 
- 
To describe the number of patients with discontinuation of SABA within the last year 
and the potential impact on disease control level and use of resources. 
 
For descriptive purposes, an analysis of the objectives will be made based on the level of 
disease control. 
 
3. RESEARCH METHODOLOGY 
 
3.1. 
Study Design  
 
A non-Interventional, descriptive, cross-sectional and unicentric study, has been designed and 
will be conducted in a Spanish hospital of Málaga. The design of the study imposes an only visit 
to be performed to obtain the patient’s signed IC and after signing it (if patient agreed to 
participate in the study), to perform an Asthma Control Test (ACT) (Appendix 2). Except for this 
study visit, the rest of study will be based on electronic medical chart review of approximately 
300 asthma patients belonging the influential area of Hospital Universitario Virgen de la 
Victoria. This chart review will be performed by the site investigator or collaborators.  
 
The data collection is stated in 6 months, and during this period the investigators will identify 
and randomly include the patients who meet selection criteria to avoid bias during patient’s 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
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inclusion. The observational period will be conformed of 12 months, and the patient’s data will 
be collected or documented in an electronic case report form (eCRF), which will automatically 
create or assign an identification numerical code to every patient the moment it’s created in 
the electronic platform. This system guarantees the anonymization of each patient included in 
the study as no identifiable information won’t be able to be captured.  
 
 
 
 
 
 
 
 
 
 
Figure 1. Overall Study design 
 
3.2. 
Study Population 
 
The study will be performed in Hospital Virgen de la Victoria, which it’s the reference hospital 
that usually attends the asthma population of its influential area. Only patients that meet the 
eligibility criteria will be included in the study, and it is planned that a total estimation of 300 
patients with asthma diagnose will be included in it. The whole patients will be recruited by the 
site investigator and collaborators, who will conduct the subject’s medical chart review. Before 
the patient’s study inclusion, the investigator team must have been obtained the signed 
informed consent (appendix 3) of each patient recruited and according to ICH GCP and to local 
legal requirements. 
 
- 
Target enrollment/ sample size: 300 patients. 
- 
Anticipated rate of enrollment: 6 months. 
- 
Estimated study start date: September 2020 
- 
Estimated study completion date: March 2020. 
 
Data collection period  (6 months) 
Observational period (12 months) / PRE-INDEX DATE 
Medical chart data to be 
reviewed and collected in the 
study 
Site initiation 
Index date 
Patient recruitment  
period 
Outcomes 

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3.2.1. Eligibility Criteria  
 
All the inclusion and exclusion criteria will be reviewed by the site investigator and 
collaborators to ensure that the patient is eligible to be included in the study. In order to be 
eligible to participate in this study, prior to the inclusion, every subject must meet the following 
selection criteria: 
 
 
3.2.1.1. 
Inclusion Criteria 
 
1. Patient with written informed consent prior to participation. 
2. Patient female or male ≥ 18 years of age 
3. Patient with asthma diagnosis more than one year before the study inclusion 
4. Clinical data available at least 1 year before the study inclusion in the electronic medical 
records. 
 
3.2.1.2. 
Exclusion Criteria 
 
1. Patient’s participation in any clinical trial during the year prior to the index date for data 
collection. 
 
 
3.2.2. Sampling  
 
An estimation of 300 asthma patients belonging to the influential area of the Hospital 
Universitario Virgen de la Victoria will be enrolled. 
 
3.3. 
Data Source / Data Collection 
 
The data source represents the information contained in original electronic medical documents 
and records (source documents) that will be necessary for the study. Primary and secondary 
endpoints will be collected from the patient’s source documents, which will be the subject’s 
medical chart. All the study data must be obtained from the source documents. 
 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
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During the 6 months of data collection period, the study variable will be gathered in an 
electronic case report form (eCRF), especially designed for the study and where each 
investigator will access through a personal user account, which will be created once the 
investigator assigns a personal password during the first access to the eCRF. Is responsibility of 
the investigator to collect all the study variables in the eCRF, from which the study data will be 
analyzed.  
 
Given the possible unavailability of certain variables, there will be the possibility in the eCRF to 
select the unavailability of the variables in the medical records. In order to avoid missing and/or 
mistaken data, it will include filters and programmable edits that will give feedback when data 
is missing, out or range or illogical. A data management plan (DMP) will be developed to 
describe all processes and specifications for data handling. 
 
The investigator/institution will facilitate study-related monitoring, audits, IRB/IEC reviews and 
regulatory inspection(s), providing direct access to all related source data and source 
documents. 
 
 
3.3.1. Endpoints  
 
3.3.1.1. 
Primary Endpoint  
1. The primary endpoint of this study is the asthma management of the study population 
according to GEMA healthcare quality indicators previously defined. For this assessment, 
it will be determined the following calculations: 
 
I. Percentage of asthmatic patients diagnosed using spirometry and bronchodilator 
(PBD) test. 
II. Percentage of patients with a diagnosed history of suspected allergic asthma 
included in a sensitization study with different allergens. 
III. Percentage of asthmatic smokers with documented recommendations for 
smoking cessation. 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
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IV. Percentage of patients included in an educational plan. 
V. Percentage of patients in treatment for persistent asthma* receiving inhaled 
glucocorticoids (ICS). 
VI. Percentage of pregnant women (if applicable) with asthma who maintain their 
treatment plan based on B2-adrenergic agonists and inhaled corticosteroids 
among the total pregnant asthmatic women recruited in the study. 
VII. Percentage of scheduled monitoring visits per patient and per year during the 
previous year among asthmatic patients with asthma monitored per year. 
VIII. Percentage of asthmatic patients with evaluation and documentation of 
exacerbations. 
 
* Persistent asthma can have asthma symptoms on more than 2 days per week and nighttime 
awakenings once or twice each month. 
 
3.3.1.2. 
Secondary Endpoint(s) 
 
o Demographic characteristics. 
▪ Age 
▪ Gender: male, female. 
▪ Ethnicity: Caucasian / Hispanic / African / Asian / Other / Unkown 
▪ Weight (kg) and height (cm): BMI autocalculated by the eCRF. 
▪ Pregnancy status (yes/no) 
▪ Smoking status (current smoker, ex-smoker*, non-smoker) 
*It will be considered that the patient is ex-smoker since the 6 months of non-
smoking. 
 
o Clinical characteristics: 
▪ Age at asthma diagnosis 
▪ Spirometry and bronchodilator test at diagnose 
▪ Patient’s derivation: primary care / specialized healthcare 

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▪ Asthma severity degree according to GEMA guidelines: Mild intermittent, 
Mild persistent, Moderate persistent and Severe persistent. 
▪ Asthma disease control level according to: 
o Clinical criteria (number of SABA canisters retired from the 
pharmacy in the previous year, number of OCS retired from the 
pharmacy in the previous year, number of emergency service 
visits in the previous year, number of unscheduled primary care 
visits in the previous year). 
o  Asthma Control Test (ACT) (most recent value available): No / 
Yes, specify score: ACT ≥ 20 points (controlled) / ACT less than 20 
uncontrolled. 
▪ History of allergic asthma (or suspected): No / Yes.  
▪ Sensitization to allergen study (for those patients with a diagnosed 
history of suspected allergic asthma). 
▪ Registration of asthma education programs performed (last asthma 
education program performed by the patient): year when it was 
performed. 
▪ Current asthma therapeutic level according to GEMA stepwise therapy 
(at patient’s inclusion date): Step 1 / Step 2 / Step 3 / Step 4 / Step 5 / 
Step 6. 
▪ Comorbidities (at patient’s inclusion date) according to Charlson 
Comorbidity Index (autocalculated). A list of diseases will be displayed in 
order to be selected those the patient suffers at the inclusion date. The 
Charlson Comorbidity index score will be autocalculated automatically by 
the eCRF.  
▪ Maintenance/long-term and reliever treatment prescribed for asthma (at 
inclusion 
date): 
type 
(SABA, 
LABA, 
GCI, 
LTRA, 
Biologic, 
immunomodulator, others), initiation date, end date or if its ongoing. 
Maintenance/long-term and reliever treatment prescribed for asthma in 
pregnant women (at inclusion date): type (SABA, LABA, GCI, LTRA, 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
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Biologic, immunomodulator, others), initiation date and end date or if its 
ongoing. 
▪ Record of scheduled monitoring asthma visits in the last year (the year 
prior since the patient’s inclusion date): register confirmation and 
number of scheduled visits performed. 
▪ History of asthma exacerbations during the last year (the year prior since 
the patient’s inclusion date): register confirmation and number of asthma 
exacerbations. 
▪ Use of health resources during the last year (the year prior since the 
patient’s inclusion date): visits to emergency department (ED), visits to 
primary health care department, visits to specialist. 
▪ Nº of emergency department (ED) and hospitalization visits 
related to an asthma diagnosis code in the last year since the 
date of study inclusion. 
- Treatment prescribed at discharge: type (SABA, OCS, 
LABA, GCI, LTRA, Biologic, immunomodulator, others). 
▪ Nº of primary health care department visits related to an 
asthma diagnosis performed during the last year since the 
date of study inclusion (scheduled and unexpected), 
▪ Nº of specialist (allergology, physiotherapy, others) visits 
related to an asthma diagnosis performed during the last year 
since the date of study inclusion.  
o Nº of oral corticosteroids (OCS) prescriptions in the last year (prior year since the 
patient’s inclusion date).  
 
 
3.4. 
Sample Size / Power Calculations 
 
To estimate a proportion of 50% (maximum variability), with a margin of error of +/- 6 
percentage points and a confidence level of 95%, a sample size 267 patients will be required. 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
17 
 
Assuming 10% of patients with non-available data from the medical records, total sample size 
must be 300 patients. 
The study sample size must allow the estimation of dichotomic variables and to determine the 
percentage of compliance of each quality care indicator established by the GEMA guidelines. 
This percentage will allow to establish the degree of compliance of each group of indicators in 
the site. 
 
The study sample size must allow the estimation of dichotomic variables and to determine the 
percentage of compliance of each quality care indicator established by the GEMA guidelines. 
This percentage will allow to establish the degree of compliance of each group of indicators in 
the site. 
Since the primary objective includes a large number of parameters and a descriptive analysis 
will be done, the sample size (N) has been calculated based on statistical criteria, using the 
criterion of maximum indeterminacy, when the percentage of one category in a categorical 
variable is expected to be around 50%. To estimate a proportion of 50%, with a margin of error 
of +/- 6 percentage points and a confidence level of 95%, a sample size 267 patients will be 
required. Assuming 10% of patients with non-available data from the medical records, total 
sample size must be 300 patients. 
 
 
3.5. 
Hypotheses  
 
Given that the primary objective aims to obtain an estimation for a population parameter, 
there is no need for a hypothesis contrast. 
 
4. DATA ANALYSIS CONSIDERATIONS  
 
Data analysis will be performed using SAS Enterprise Guide Version 7.15, and a statistical 
analysis plan will be designed and agreed before the data analysis initiation. 
All the analyzes will be performed by descriptive statistical methods of all the variables 
separately. All the patients participating in the study who met the eligibility criteria will be 
included in the study population. 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
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The quantitative data will be described by the following statistical parameters: number of valid 
patients (N valid), number of missing data (N missing), mean, standard deviation, median, inter-
quartile range, minimum and maximum will also be presented. 
The qualitative data will be presented through the length-frequency distributions (absolute and 
relative). For both cases, the following will be specified: number of observations (N) and 
number of missing data (N missing). 
 
Primary objective: 
To analyze the primary objectives, it will be assessed the percentage of compliance of each 
asthma quality care indicator established by GEMA guidelines (GEMA 4.4, Guía Española para el 
Manejo del Asma): 
 
GROUP I. Diagnosis 
- 
Diagnostic confirmation by spirometry and bronchodilator test. To know the compliance 
of this indicator, it will be calculated the percentage of asthmatic patients diagnosed 
using spirometry and bronchodilator test will be determined: 
Nº patients diagnosed with asthma using spirometry x 100 / nº patients 
diagnosed with asthma 
- 
Sensitization study in allergic asthma. To know the compliance of this indicator, it will be 
calculated the percentage of patients with a diagnosed history of suspected allergic 
asthma included in a sensitization study with different allergens: 
Nº of patients with a diagnosed history of suspected allergic asthma included in a 
sensitization study with different allergens x 100 / nº patients diagnosed with 
asthma (and diagnosed history of suspected allergic asthma?) 
 
GROUP II. Non-pharmacological treatment 
- 
Smoking cessation. To know the compliance of this indicator, it will be calculated the 
percentage of asthmatic smokers with documented recommendations for smoking 
cessation: 

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Nº of asthmatic smokers with a documented recommendation for smoking 
cessation x 100 / nº asthmatic smokers  
- 
 Educational plan for patients with asthma. To know the compliance of this indicator, it 
will be calculated the percentage of patients included in an educational plan: 
Nº of patients with asthma included in an educational plan x 100 / Nº of patients 
with asthma  
 
GRUPO III. Pharmacological treatment 
- 
Treatment of choice for persistent asthma.  To know the compliance of this indicator, it 
will be calculated the percentage of patients in treatment for persistent asthma who are 
receiving inhaled glucocorticoids (ICS): 
Nº of patients in treatment for persistent asthma receiving inhaled 
glucocorticoids (at patient’s inclusion date) x 100 / Nº of patients in treatment for 
persistent asthma 
- 
Treatment for asthma in pregnant women. To determine the compliance of this 
indicator, it will be calculated the percentage of pregnant women (if applicable) with 
asthma who maintain their treatment plan based on B2-adrenergic agonists and inhaled 
corticosteroids among the total pregnant asthmatic women recruited in the study: 
Nº of pregnant women with asthma patients who maintain their treatment plan 
based on β2-adrenergic agonists and inhaled corticosteroids x 100 / Nº of 
pregnant women receiving asthma maintenance treatment 
 
GRUPO IV. Monitoring 
- 
Periodic monitoring of patients. To determine the compliance of this indicator, it will be 
calculated the percentage of scheduled monitoring visits per patient and per year during 
the previous year among asthmatic patients with asthma monitored per year: 
Nº of scheduled (not unexpected) monitoring visits per patient and per year x 100 
/ Nº of patients with asthma monitored per year. 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
20 
 
- 
Periodic monitoring of exacerbations. To determine the compliance of this indicator, it 
will be calculated the percentage of asthmatic patients with evaluation and 
documentation of exacerbations: 
Nº of patients with asthma with evaluation and documentation of exacerbations 
during the last year x 100 / Nº of patients with asthma  
 
 
The interpretation of the result will be subject to the subsequent Statistical Analysis Plan (SAP) 
which will be determine whether an interpretation of the results obtained will be made or if it 
will be based on a descriptive definition thereof. 
 
 
In order to describe the secondary endpoint, the following measures will be described: 
• Sociodemographic and clinical characteristics: A descriptive analysis will be performed 
of the patient’s sociodemographic and clinical characteristics collected.  
• Treatment patterns: To evaluate this endpoint it will be performed a treatment 
description of the long-term treatment and the reliever therapy (if applicable). 
• To describe the disease control level in the study population. A descriptive analysis will 
be performed of the disease control level. 
• Use of assistance health resources (secondary objective 3): resource use will be 
evaluated as number of visits performed by the patient the prior year to the inclusion 
date: 
o Emergency department (ED) linked to asthma. 
o Hospitalizations linked to asthma. 
o Primary care visits (scheduled and unexpected) linked to asthma. 
o Specialist visits (allergists, pulmonologists, etc.) linked to asthma. 
• To describe the number of patients with discontinuation of SABA within the last year: It 
will be described the number of patients with SABA discontinuation during the prior 
year of the study inclusion date.  
•  
 
 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
21 
 
5. LIMITATIONS 
 
As this is a study based on the usual clinical practice and given the real-world nature of the 
data, the main limitation is the availability of study variables in the subject’s medical charts. 
 
 
6. STUDY CONDUCT, MANAGEMENT & ETHICS 
 
6.1. 
Ethics Committee/IRB Approval  
 
This non-interventional study will be initiated once all required legal documentation has been 
reviewed and approved by the Independent Ethics Committee (IEC) and it will be conducted in 
accordance with the protocol, the current version of the Declaration of Helsinki, Good 
Pharmacoepidemiology Practices (GCP) and any local regulations.  
 
The appointed CRO or the Site Study Responsible will submit required documents to the IEC, 
such as period updated during the study progress, the notification of study ending, the 
summary of the study results, as well as any relevant amendment.  
 
6.2. 
Informed Consent 
 
Prior to patient participation in the study, written informed consent will be needed from each 
patient (or the patient’s legally accepted representative). 
 
The collection of patient’s Informed Consent will be performed in accordance with the IRB/ERC 
requirements, applicable laws and regulations (General Data Protection Regulation (GDPR) (EU) 
2016/679) and Sponsor requirements  
 
6.3. 
Data Protection 
 
The patient’s data will be collected or documented in an electronic case report form (eCRF), 
specially designed for the study, which will automatically create or assign the identification 
numerical code to every patient the moment it’s created in the platform. All the individual 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
22 
 
patient medical information is considered confidential, and its confidentiality will be 
guaranteed as no subject’s personal information will be captured during the study. 
 
The eCRF will be the source of information of the study and whose information will be 
analyzed. The eCRF is a web-based application accessible on any computer with an Internet 
connection. The 128 bit SSL protocol will be used for Web communications, ensuring 
confidentiality of communications between servers and the investigator’s computer by 
encrypting all the results sent (a “secure connection”). 
The e-CRF will allow defining filters in collected variables in order to avoid mistakes, as well as 
to obtain statistics about the main outcomes in real time. The e-CRF will include specific logic 
checks and filters for collected variables in an effort to minimize errors in data entry. The e-CRF 
will also allow the study team to obtain statistics on recruitment and e-CRF completion 
progression in ‘real-time’. The web application is developed with the following technology: 
 
• ASP.NET  
• RDBMS SQL SERVER 
• SSL (128bits)  
• WEB server O.S. Windows  
 
The SSL technology implemented guarantees that all data transferred to the CRO database 
server will be encrypted and protected from external attacks. An audit trail process will assure 
the control of every movement made to the data stored. Information registered for every value 
stored in the database includes: the event date, responsible party, variable, old value, new 
value, and the type of action taken (creation, updating or deleting). This audit process provides 
an additional security mechanism for stored data and may also be useful in answering data 
entry questions by site personnel. 
Furthermore, a data Management Plan (DMP), will be also developed to detail how data will be 
handled. Active ingredients entered into the database will be coded using ATC codes. Medical 
history/current medical conditions will be coded using the Medical dictionary for regulatory 
activities (MedDRA) terminology. 
 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
23 
 
 
It will be paid special attention to data protection, which will be guaranteed according to the 
applicable laws and regulations (General Data Protection Regulation (GDPR) (EU) 2016/679) and 
the corresponding local regulations (Ley Orgánica 3/2018, de 5 de diciembre, de Protección de 
Datos Personales y garantía de los derechos digitales), that will be fully respected during the 
whole study.  
 
6.4. 
Personally Identifiable Information (PII) 
 
The individual patient medical information is considered confidential for all purposes and it’s 
disclosure to third parties is prohibited with the exceptions indicated below. To guarantee 
patient’s confidentiality, all the data entered in the eCRF during the data collection will be 
previously anonymized and dissociated as the patient included in the study will be 
automatically assigned to an identification numerical code the moment when it’s created 
within the eCRF. The study database will never contain any personal data that could identify the 
patient, so it will remain always protected.   
 
Only in special cases when it might be necessary to know the patient’s identification, the 
sponsor must follow the confidentiality standards according to the local regulations; Ley 
Orgánica 3/2018, de 5 de diciembre, de Protección de Datos Personales y garantía de los 
derechos digitales. 
 
Regarding study results publication, the rights of the investigator and the sponsor with this 
respect will be described in the study contract. As general rule, no results of the study will be 
published before the end of the clinical study report.  
The clinical study report will be submitted to national health authorities and the corresponding 
international ethics committee. The results of the study may be also published.  
 
Through the signature of this protocol, the investigator guarantees the sponsor that all the 
information disposed by the sponsor will remain confidential.  
 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
24 
 
 
 
6.5. 
Adverse Event (AE), Pregnancy Exposure, and Incident Reporting 
 
This is a non-interventional study in which no drug will be studied nor administered, so 
systematic collection of adverse events does not apply. If any adverse event had occurred 
during the retrospective period of the study, they should have already been notified as dictated 
by national regulation “Real Decreto 577/2013, de 26 de julio por el que se regula la 
farmacovigilancia de medicamentos de uso humano”. 
 
If any of the patients included in the study presented an adverse reaction during the study visit, 
the duty of the investigator will be to act in accordance with the guidelines of the 
aforementioned regulation and proceed to notify and send it as quickly as possible to the 
competent body of pharmacovigilance (www.notificaRAM.es), in this case of the autonomous 
community of Andalusia. 
 
6.5.1. Definitions of adverse events 
 
Adverse reaction: An adverse reaction is defined as any response to a medicinal product which 
is noxious and unintended, and that takes place at doses used that are normally applied in 
humans for the prophylaxis, diagnosis or treatment of diseases, or for the restoration, 
correction or modification of physiological functions. 
 
Serious adverse event or serious suspected adverse reaction: an adverse event or suspected 
adverse reaction is considered “serious” if it results in any of the following outcomes: Death, a 
life-threatening adverse event, inpatient hospitalization or prolongation of existing 
hospitalization, a persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions, or a congenital anomaly/birth defect. Important medical events 
that may not result in death, be life-threatening, or require hospitalization may be considered 
serious when, based upon appropriate medical judgment, they may jeopardize the patient or 
subject and may require medical or surgical intervention to prevent one of the outcomes listed 
in this definition. 
 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
25 
 
 
7. EXTERNAL INVOLVEMENT 
7.1. 
Third Party Supplier  
IQVIA Information 
 
7.2. 
External Expert/Health Care Professionals (Consultants & Research PIs)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
26 
 
APPENDIX 1. Quality assistance indicators – GEMA Guidelines 
 
INDICATOR 
GROUPS 
INDICATOR 
CALCULATION 
I. Diagnosis 
1. Diagnostic confirmation by spirometry 
with bronchodilator test. Diagnostic 
confirmation of patients with asthma is 
performed with spirometry and 
bronchodilator test as an objective measure 
of functional involvement. 
Number of patients with asthma with 
spirometry performed x100/number 
of patients diagnosed with asthma. 
2. Sensitization study in allergic asthma. 
Patients with suspected allergic asthma 
should be screened for possible 
sensitizations to different allergens. 
Number of patients diagnosed with a 
history suggestive of allergic asthma 
with a sensitization study performed 
to different allergens x100/number of 
patients diagnosed with asthma. 
II. Non-
pharmacological 
treatment 
3. Smoking cessation. Smoking cessation is 
recommended in smoking patients with 
asthma. 
Number of asthma patients with 
smoking and registered dishabituation 
recommendation x100/asthma 
patients with smoking. 
4. Educational plan for patients with 
asthma. Patients with asthma should follow 
a basic education program (consisting of: 
knowledge about their disease, about its 
treatment, action plan and inhalation 
technique, written document) as part of 
their treatment. 
No. of asthma patients with asthma 
education program x100/no. of 
asthma patients. 
III. 
Pharmacological 
treatment 
5. Treatment of choice in persistent asthma. 
The treatment of choice in persistent asthma 
includes inhaled glucocorticoid (ICG) used 
daily. In some justified cases, leukotriene 
receptor antagonists may be considered as 
an alternative treatment. 
Number of patients on control 
treatment for persistent asthma 
receiving GCI x 100/number of 
patients on control treatment for 
persistent asthma. 
6. Treatment of asthma in pregnant 
women. In the maintenance treatment of 
asthma in pregnant women, it is 
recommended to maintain the drugs usually 
used ( β2-adrenergic agonists and inhaled 
glucocorticoids). 
No. of women with asthma who 
maintain their usual treatment ( β2-
adrenergic agonists and inhaled 
glucocorticoids) in pregnancy 
x100/number of pregnant women 
with asthma on maintenance 
treatment. 
IV. Follow-up 
7. Periodic follow-up of patients. Need for 
regular follow-up of patients, even if they 
have not had exacerbations, through 
scheduled medical visits. 
Number of scheduled (non-
unplanned) follow-up visits per 
patient per year x100/number of 
asthma patients followed up per year. 
8. Periodic recording of exacerbations. The 
specific assessment of exacerbations is 
evaluated periodically. 
Number of asthma patients in whom 
exacerbations have been evaluated 
and documented x100/number of 
asthma patients. 
 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
27 
 
APPENDIX 2. Asthma Control Test (ACTTM)  
 
https://www.asthmacontroltest.com/en-gb/welcome/ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
28 
 
 
APPENDIX 3. Patient Information Sheet and Informed Consent Form 
PATIENT INFORMATION SHEET 
 
Study title: "Observational, descriptive, cross-sectional and single-center study to describe the clinical 
management in asthmatic patients in the area of influence of the Virgen de la Victoria University 
Hospital in Malaga" 
 
Introduction 
A research study is being carried out at this health centre and you are invited to participate. The study 
has been approved by the corresponding Research Ethics Committee and the Spanish Agency for 
Medicines and Health Products and will be carried out in accordance with current legislation, Royal 
Legislative Decree 1/2015 approving the revised text of the Law on guarantees and rational use of 
medicines and medical devices.  
Your participation is voluntary and will be confirmed, if you so choose, with your signature at the end of 
this document. In this respect, you can change your decision and withdraw your consent to participate 
at any time, without giving any reasons and without affecting your health care. The intention is that you 
receive adequate and sufficient information so that you can assess and decide whether or not you want 
to participate in this study. To do this, read this fact sheet carefully and your study doctor will answer 
any questions you may have.  
 
Why is this study going to be carried out? 
The main objective of this study is to describe the clinical management of asthmatic patients in the area 
of influence of the Virgen de la Victoria University Hospital, i.e. all health centers whose reference 
hospital is said hospital, according to the quality-of-care indicators established by the Spanish Guide for 
the Management of Asthma (GEMA). 
 
How will the study be conducted? 
The study consists of a single visit, in which you will be offered to participate in this study. Once you 
have consented to participate in the study and the selection criteria for participation in the 
study have been confirmed, information will be collected from your medical history of a 
demographic nature (age, gender, ethnicity, smoking habit, height and weight) and also related to your 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
29 
 
asthma disease (age at diagnosis, spirometric diagnostic data,  degree of severity, current treatment, 
history of exacerbations, etc.) 
You will also be asked to take a test to assess your level of asthma control (Asthma Control Test - 
ACTTM) at your study visit, which consists of a 5-question test that will take you less than 5 minutes to 
complete. Except for this test, all the information will be completed by the investigating physician based 
on the data available in the patient's medical record, without the study protocol requiring 
determinations and tests that were not previously carried out and that are not part of the usual routine 
regardless of whether you participated in the study or not. 
 
What will I have to do in this study, how long will I be in the studio? 
Your participation in this study will last only the time of this scheduled visit and in which you will 
perform the Asthma Control Test, mentioned above. 
 
Potential Benefits 
You may not personally benefit from your participation in this study, but it may provide new 
information that will benefit other patients and be useful to the medical-scientific community 
for the treatment of asthma.  
 
What happens to my personal data? In accordance with current data protection regulations 
(Organic Law 3/2018, of 5 December, on the Protection of Personal Data and Guarantee of Digital Rights 
(LOPD) and Regulation (EU) 2016/679 of the European Parliament and of the Council of 27 April 2016 on 
the protection of natural persons with regard to the processing of personal data and on the free 
movement of such data (GDPR),  You expressly consent to the inclusion of the data from your medical 
history, as well as those resulting from your participation in the study in a personal data file under the 
responsibility of the centre.  Access to your personal information will be restricted to the study doctor 
and his collaborators, health authorities, the Clinical Research Ethics Committee and the monitors, 
auditors and other personnel authorized by the sponsor, who will be subject to the duty of secrecy 
inherent to their profession, when necessary, to verify the data and procedures of the study.  but always 
maintaining the confidentiality of these in accordance with current legislation. 
The data collected in the study will be identified by a code and only your study doctor and collaborators 
will be able to relate this data to you and your medical history. Therefore, your identity will not be 
revealed to any person except in case of medical emergency or legal requirement in the terms indicated 
above.   

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
30 
 
INFORMED CONSENT 
 
 
Patient Number: _________________________________ 
 
My signature on this informed consent form means that: 
- 
I have read the information sheet that has been given to me and I have understood the 
information provided. 
- 
I understand that I am being asked if I wish to participate in an observational study that has been 
designed to describe the clinical management of asthmatic patients in the area of influence of the 
Virgen de la Victoria University Hospital in accordance with the quality-of-care indicators 
established by the Spanish Guide for the Management of Asthma (GEMA). 
- 
I have received enough information about the study 
- 
I have been able to ask questions about the study, receiving complete and satisfactory answers to 
all my questions. 
- 
I understand that my participation is voluntary. 
- 
I understand that I can withdraw from the study: 
• 
When I want 
• 
Without having to explain 
• 
Without this having an impact on my medical care. 
 
I freely consent to participate in the study and consent to the access and use of my data under the 
conditions detailed in the information sheet. 
 
 
 
_____________________________ 
        ____________________________      _____________ 
Name and surname of the study 
        Signature of consent of the study      Date 
participant 
 
 
 
        participant 
 
 
 
 
_____________________________ 
        ____________________________         _____________ 
Name and surname of the doctor 
        Signature of consent of the doctor      Date  
            
in the study who obtains consent 
        in the study who obtains consent 
 

Protocol V.1.0 – 1st of December 2019  
 
 
 
 
31 
 
8. BIBLIOGRAPHY 
 
1. Urrutia I, Aguirre U, Sunyer J, Plana E, Muniozguren M, Martínez J, et al. Cambios en la 
prevalencia del asma en la población española del Estudio de Salud Respiratoria de la 
Comunidad Europea (ECRHS-II). Arch Bronconeumol. 2007; 43: 425-30. 
 
2. Peters, S. P., Ferguson, G., Deniz, Y., & Reisner, C. (2006). Uncontrolled asthma: A review of 
the prevalence, disease burden and options for treatment. Respiratory Medicine, 100(7), 1139–
1151.). 
 
3.  Rabe, K. F., Vermeire, P. A., Soriano, J. B., & Maier, W. C. (2000). Clinical management of 
asthma in 1999: the Asthma Insights and Reality in Europe (AIRE) study. European Respiratory 
Journal, 16(5), 802–807. 
 
4.  Accordini, S., Corsico, A., Cerveri, I., Gislason, D., Gulsvik, A., … Janson, C. (2007). The socio-
economic burden of asthma is substantial in Europe. Allergy, 63(1), 116–124. 
 
5. Nunes, C., Pereira, A. M., & Morais-Almeida, M. (2017). Asthma costs and social impact. 
Asthma Research and Practice, 3(1). doi:10.1186/s40733-016-0029-3 
 
6. Martínez-Moragón, E., Serra-Batllés, J., De Diego, A., Palop, M., Casan, P., Rubio-Terrés, C., & 
Pellicer, C. (2009). Coste económico del paciente asmático en España (estudio AsmaCost). 
Archivos de Bronconeumología, 45(10), 481–486 
 
7. S Quirce, et al: Prevalence of Uncontrolled Severe Persistent Asthma in Pneumology and 
Allergy Hospital Units in Spain). 
 
8. Guía Española para el Manejo del Asma (GEMA). Available from: http://www.gemasma.com 
 
9. Global Initiative for Asthma (GINA). Available from: https://ginasthma.org 

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10. Partridge, M. R., van der Molen, T., Myrseth, S.-E., & Busse, W. W. (2006). Attitudes and 
actions of asthma patients on regular maintenance therapy: the INSPIRE study. BMC Pulmonary 
Medicine, 6(1). 
 
11. Rabe, K. F., Adachi, M., Lai, C. K., Soriano, J. B., Vermeire, P. A., Weiss, K. B., & Weiss, S. T. 
(2004). Worldwide severity and control of asthma in children and adults: the global asthma 
insights and reality surveys. Journal of Allergy and Clinical Immunology, 114(1), 40–47. 
 
12. Magnoni, M. S., Latorre, M., Bettoncelli, G., Sanchez-Herrero, M. G., Lopez, A., Calvo, E., … 
Paggiaro, P. (2017). Asthma control in primary care: the results of an observational cross-
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and 
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doi:10.1186/s40413-017-0144-5 
 
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Fueyo A, Ruiz MA, Ancochea J, Guilera M, Badia X; ESCASE Group. Asthma control in 
Spain. Do season and treatment pattern matter? The ESCASE study. Respir Med. 2007; 101: 
919-24. 
 
 14. De Miguel Díez, J. (2005). Farmacoeconomía en el asma y en la EPOC. Archivos de 
Bronconeumología, 41(5), 239–241.  
 
15. Plaza Moral V. Farmacoeconomía del asma. Med Clin Monogr (Barc). 2003;3 Supl 1:49-53 
 
16 . Stock S, Redaelli M, Luengen M, Wendland G, Civello D, Lauterbach KW. Asthma: 
prevalence and cost of illness. Eur Respir J. 2005;25:47-53. 
 
17. Plaza Moral V, Álvarez Gutiérrez FJ, Casan Clarà P, Cobos Barroso N, López Viña A, Llauder 
Rosselló MA, et al. Guía española para el manejo del asma. Arch Bronconeumol. 2003;39 Supl 
5:3-42.