A Study to Evaluate the Symptoms Over 24 Hours in Patients With Chronic Obstructive Pulmonary Disease - LASSYC Study
A Study to Evaluate the Symptoms Over 24 Hours in Patients With Chronic Obstructive Pulmonary Disease - LASSYC Study
No previous studies have evaluated the frequency and severity of Chronic Obstructive
 Pulmonary Disease (COPD) symptoms over a period of 24 hours (early morning, daytime and
 nigth-time symptoms) in stable COPD patients seen in clinical practice in Brazil. COPD is a
 common disease seen by primary care physicians and one of the most common diseases referred
 and diagnosed by pulmonologists. According to previous studies, symptoms of COPD can have a
 substantial impact on patients' quality of life and present a considerable degree of
 variation for the same degree of airflow limitation.

 The objective of this study is to learn more about the burden of symptoms in the real-world
 population of COPD patients in Brazil. With the real life data coming from this study, it
 will be possible to describe 24-hour COPD symptoms in Brazil and their impact on patients'
 quality of life and other PROs, the relationship with patients´ behaviour regarding adherence
 to respiratory medication and burden of COPD symptoms in terms of the impact on health
 economics.

 In the present study, the investigators will assess and characterize COPD symptoms over a
 period of 24 hours, by collecting information about the respiratory symptoms experienced at
 different times of the day and night in patients with stable COPD under real clinical
 practice conditions. In addition, the investigators will evaluate the correlation between
 each of these symptoms and the GOLD classification, adherence to respiratory treatment, level
 of dyspnea, disease severity, comorbidities and physical activity. Finally, the investigators
 will assess the relationship between 24h symptoms and direct cost related to treatment and
 HRU in the previous year to assess the burden of COPD symptoms.

 The present study is based on a similar protocol applied in Latin-American patients, the
 LASSYC Study. Extracted data will be used for a Brazilian analysis of these outcomes and may
 be used in future analyses combined with the results of LASSYC Study for a global view of
 Latin America.
Background

 Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable disease with some
 significant extrapulmonary effects that may contribute to the severity in individual
 patients. Its pulmonary component is characterized by airflow limitation that is not fully
 reversible. The airflow limitation is usually progressive and associated with an abnormal
 inflammatory response of the lung to noxious particles or gases (i). Although smoking is one
 of the major and most frequent causes of COPD, other factors may be associated with its
 development. The narrowing of the airways, which is one of the main features of COPD, results
 from a combination of small airway disease and parenchymal destruction, as well as structural
 changes from the chronic inflammatory process. For this reason bronchoconstriction is one of
 the key targets of pharmacological interventions in the management of COPD.

 This disease affects globally around 15% of all adults older than 40 years, resulting in
 pulmonary and extrapulmonary comorbidities and significant mortality (1,ii). The worldwide
 prevalence in people aged over 40 years is 10.1% overall, 11.8% for men, and 8.5% for women,
 according to the BOLD Study (iii). It is the fourth leading cause of death in the world and
 its prevalence is projected to increase in the coming years due to continued exposure to COPD
 risk factors (1). Two Latin-American epidemiological studies, the PLATINO Project iv and
 PREPOCOL v, have provided information on the prevalence of COPD in this region. PLATINO is a
 study on prevalence of COPD in individuals ≥40 years, carried out in five Latin American
 cities: Mexico City (Mexico), São Paulo (Brazil), Montevideo (Uruguay), Santiago de Chile
 (Chile), and Caracas (Venezuela). Using as diagnostic criteria post-BD FEV1/FVC ratio
 &lt;0.70, the overall prevalence of COPD in PLATINO is 14.3% (ranging from 7.8% in Mexico
 City to 19.7% in Montevideo) and in the city of São Paulo is 15.8 % (4,vi). Using the lower
 limit of normal criteria (LLN) of the post- BD FEV1/FVC ratio, the global COPD prevalence in
 PLATINO is 11.7%. This is even lower (9.5%) when using the post-BD FEV1/VEF6 &lt; LLN ratio
 (vii). PREPOCOL (5) assessed the prevalence in five cities in Colombia and reported an
 overall prevalence of 8.9% (from 6.2% in Barranquilla to 13,5% in Medellin).

 Symptoms of COPD - including progressive dyspnea, chronic cough, excessive sputum production
 and decreased exercise tolerance - may considerably affect the patients' daily activities and
 quality of life (1,viii,ix). COPD symptoms have been reported to be worse at night and in the
 early morning (x,xi), which may be reflected in disturbed sleep and limitations on morning
 activities.

 Moreover, the health-related quality of life (HRQoL) is being recognized as an important
 outcome when evaluating patients with COPD and several studies have demonstrated that those
 patients in more severe disease stages presented worse HRQoL and it varied greatly within
 each stage of disease severity (xii).

 From the patient´s point of view, dyspnea is one of the major symptoms that affect their
 quality of life (xiii). However, dyspnea varies considerably for the same degree of airflow
 limitation.

 It is reported that poor patient's adherence to inhaled medication is shared by COPD and
 asthma patients (xiv). Non-adherence to inhaled therapy is associated with inadequate symptom
 control, higher healthcare utilization and costs, as well as decreases in health-related
 quality of life (12- 14). In practice guidelines of the Global Initiative for Asthma
 Management [GINA) (xv) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) (1)]
 is now specifically recommended evaluation and follow-up of the patient's adherence to
 inhaler devices.

 Previous studies (xvi, xvii, xviii, xix) have shown that physical activity in COPD is
 associated with a better quality of life and less morbidity and mortality. In addition,
 comorbid conditions such as cardiovascular disease, anxiety and depressive disorders, lung
 cancer and osteoporosis are frequently observed in COPD patients and may affect COPD outcomes
 (xx). Sleep disorder is also common in COPD patients. In epidemiologic studies, more than 50%
 of patients with COPD complained of difficulty to maintain and initiate sleep, and 25%
 complained of excessive daytime sleepiness (xxi). The COTE Index establishes the relationship
 between these main comorbidities and the risk of death over a median of 51 months. This is a
 simple, disease-specific comorbidity index that helps assess the risk of mortality in
 patients with COPD (xxii).

 It has been recently published the ASSESS Study (xxiii) regarding a cohort of 727 European
 patients. This observational study assessed the prevalence, severity and relationship between
 nighttime, early morning and daytime COPD symptoms and explored the relationship between
 24-hour symptoms and other results reported by DPOC patients. It was shown that more than
 half of patients experienced COPD symptoms throughout the whole 24-hour period, and there was
 a significant relationship between them and the worse patient-reported outcome, suggesting
 that improving 24- hour symptoms should be an important consideration in the management of
 COPD.

 COPD is associated with a substantial economic burden due to direct healthcare costs e.g.
 unplanned medical visits and hospitalization due to exacerbations (1,xxiv). More frequent
 exacerbations are associated with: more frequent/longer hospital stays; increased mortality
 risk; reduced quality of life (xxv); as well as indirect/societal costs due to loss of
 productivity and premature death in patients with COPD further increasing the economic burden
 of this disease (1,24-xxvi).

 Rationale

 No previous studies have evaluated the frequency and severity of COPD symptoms over a period
 of 24 hours (nighttime, early morning and daytime symptoms) in stable COPD patients seen in
 clinical practice in Brazil. COPD is a common disorder seen by primary care physicians and
 one of the most common diseases referred and diagnosed by pulmonologists. According to
 studies, COPD symptoms can have a substantial impact on patients' quality of daily life and
 present a considerable degree of variation for the same degree of airflow limitation.

 This study aims to learn more about the burden of symptoms in the real-world population of
 COPD patients in Brazil. With the real life data from this study, it will be possible to
 describe 24-hour COPD symptoms and their impact on patients' quality of life and other PRO,
 the relationship with patients' behaviour regarding adherence to respiratory medication and
 the burden of COPD symptoms in terms of the impact on health economics in Brazil.

 In the present study, the investigators will assess and characterize COPD symptoms over a
 period of 24 hours, by collecting information about the respiratory symptoms experienced at
 different times of the day and night-time in patients with stable COPD under real clinical
 practice conditions. In addition, the investigators will evaluate the correlation between
 each of these symptoms and the 2013 GOLD classification, adherence to respiratory treatment,
 level of dyspnea, disease severity, comorbidities and physical activity. Finally, the
 investigators will assess the relationship between 24h symptoms and direct cost related to
 treatment and HRU in the previous year to assess the burden of COPD symptoms.
INCLUSION CRITERIA

 Patients will only be included in the study if they meet all of the following criteria:

 1. Male or female patients aged 40 years or older.

 2. Patient diagnosed with COPD for 1 year or more.

 3. Patient presenting at least one spirometry with COPD criteria, FEV1/FVC fixed ratio
 &lt;0.70 post BD, in the last 12 months.

 4. Patient is a current smoker or an ex-smoker with a smoking history of ≥ 10 pack-
 years.

 5. Stable patients, as stated in medical records or patient reports during visit, defined
 as: without treatment due to exacerbation at study visit or within the previous 2
 months, and without changes in maintenance COPD treatment regimen over the preceding 2
 months (avoid first-time patient from participating in the study).

 6. Patients must be able and willing to read and understand written instructions, and
 understand and complete the questionnaires required by the protocol.

 7. After receiving full explanation, patients must have signed an informed consent
 document indicating that they understand the purpose of and the procedures required
 for the study and are willing to participate in the study.

 EXCLUSION CRITERIA

 Patients who meet any of the following criteria will not be eligible to participate in the
 study:

 1. Patient with a diagnosis of sleep apnea syndrome or other chronic respiratory disease
 different from chronic obstructive diseases.

 2. An acute or chronic condition that, in the investigator's opinion, would limit
 patient's ability to complete the questionnaires or participate in this study.