The Effect of Beclomethasone/Formoterol in Extra-fine Formulation on Quality of Life and SAD in COPD Patients.

Study Overview
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Brief Summary
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In patients with chronic obstructive pulmonary disease (COPD), small-airway dysfunction (SAD) is considered a key element and a functional consequence of the pathology. However, the exact role of SAD as a specific 'pharmacological target' is not yet fully known. Objectives In an open-label prospective study, we aimed to ascertain whether an extra-fine formulation of Beclomethasone dipropionate/Formoterol fumarate (BDP/FF) NEXThaler® 100/6 μg b.i.d. can improve the impact of the disease on the quality of daily life of COPD patients, acting on SAD. Methods We studied COPD patients with severe airflow obstruction and 1 moderate exacerbation in the previous year, being treated with BDP/FF NEXThaler® for 12 weeks. They underwent three visits, at the start of the treatment (V1), at 6th week (V2) and at 12th week (V3). By the impulse oscillometry system and by spirometry and plethysmography we measured at each visit the fall in resistance from 5 to 20 Hz (R5-R20) and the residual volume/total lung capacity (RV/TLC). COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) questionnaire were also measured at each visit to assess the impact of the disease on the quality of life of the patients.

Detailed Description
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In recent years, there has been a growing interest in deepening the contribution of small airways (with a diameter <2mm) to the clinical expression of Chronic Obstructive Pulmonary Disease (COPD). In patients with stable COPD, SAD severity was found to be progressively increased both with the degree of airflow obstruction and with GOLD risk class. Moreover, a correlation between SAD and COPD impact measured with the CAT (COPD Assessment Test) was found, being the severity of SAD a predictor of the impact of the disease (CAT≥10). A close correlation between SAD and both quality of life (measured with the St. George's Respiratory Questionnaire) and perceived dyspnea (measured with the modified Medical Research Council-mMRC scale) was also found in COPD patients. The exact role of SAD as a specific 'pharmacological target' is not yet fully known. According to the guidelines, the administration of combination such as Beclomethasone dipropionate/Formoterol fumarate (BDP/FF) in extra-fine formulation produced a clinically relevant improvement in quality of life (> 4 units in the St. George's Respiratory Questionnaire) and in dyspnea. However, it is not yet defined whether exists a correlation between symptomatic improvement and SAD and whether an improvement of symptoms can be achieved acting pharmacologically on SAD. The rationale for this study is based on the hypothesis that an extra-fine formulation of BDP/FF, designed to target the entire bronchial three, included the peripheral zone, can improve the impact of the disease on the quality of life of COPD patients, acting on SAD. The functional indices of SAD used in this study are from the impulse oscillometry system (IOS), the standard spirometry and the body plethysmography. The primary endpoint of the study was, therefore, an improvement of the impact of the disease on quality of daily life (CAT) and of dyspnea (mMRC) after 12th week treatment with an extra-fine formulation of BDP/FF in a cohort of COPD patients with severe airway obstruction and one moderate exacerbation in a previous year; secondary endpoint was an improvement of the SAD at the 12th week in these patients.

Official Title
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The Effect of Beclomethasone/Formoterol in Extra-fine Formulation on Quality of Life and Dyspnea is Associated to the Improvement in Small Airway Dysfunction in COPD Patients. A Pilot Study (IOSCOPD20161102)

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Beclomethasone Dipropionate/Formoterol Fumarate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: a documented diagnosis of COPD defined according to the guidelines of the American Thoracic Society (ATS) / European Respiratory Society (ERS); smokers or former smokers with a smoking history of at least 10 pack / years; subjects with a post-bronchodilator forced expiratory volume at the 1st second (FEV1)/ forced vital capacity (FVC) ratio of < 0.7 and a FEV1 <50% pred; subjects with a high impact of the COPD on their health status (CAT≥10); clinical history of at least 1 moderate exacerbation / year; COPD patients being treated with BDP/FF NEXThaler® 100/6 μg in extra-fine formulation no more than 1 (one) week before enrollment. Exclusion Criteria: an exacerbation in the four weeks prior to enrollment; other coexisting lung diseases (bronchial asthma, restrictive diseases or bronchiectasis) and severe co-morbidities associated with COPD, such as uncontrolled cardiovascular disease, pneumonia or cancer; pregnant patients; subjects unable to meet the criteria of acceptability and repeatability of pulmonary function tests, according to the ATS / ERS document

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 43 COPD<br>COPD patients with severe airflow obstruction and 1 moderate exacerbation in the previous year being treated with BDP/FF NEXThaler® 100/6 μg b.i.d. for 12 weeks | Drug: Beclomethasone Dipropionate/Formoterol Fumarate<br>* BDP/FF NEXThaler® 100/6 μg b.i.d.<br>* Other names: Foster NEXThaler®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change (Improvement) of CAT (Italian version) | The CAT (COPD Assessment Test) is a questionnaire suitable for completion by all patients diagnosed with COPD. It comprises 8 simple questions that most patients should be able to understand and complete independently. The CAT has a scoring range of 0-40, where each question is ranging 0-5. A CAT score>10 indicates a medium/high impact level of COPD. A difference or change of 2 or more units over 2 to 3 months in a patient suggests a clinically significant difference or change in health status (minimal clinically relevant change, often referred to as the Minimum Clinically Important Difference or MCID). | Change from Baseline CAT at 12th week | 
| Change (Improvement) of mMRC (Italian version) | The modified Medical Research Council (mMRC) dyspnoea scale is a questionnaire that consists of five statements about perceived breathlessness: grade 1, I only get breathless with strenuous exercise; grade 2, I get short of breath when hurrying on the level or up a slight hill; grade 3, I walk slower than people of the same age on the level because of breathlessness or have to stop for breath when walking at my own pace on the level; grade 4, I stop for breath after walking 100 yards or after a few minutes on the level; grade 5,  I am too breathless to leave the house. Patients are asked about their perceived breathlessness and are then classified into MRC dyspnoea grades according to how they perceive their disability. | Change from Baseline mMRC at 12th week | 
| Change (Improvement) of R5-R20 (kPa x s x L-1) | The IOS was performed with the Jaeger MasterScreen-IOS device following the standard recommendations. Respiratory resistances at 5 Hz and 20 Hz (R5 and R20, kPa x s x L-1) were used as a total and proximal airway resistance index, respectively, and the resistance drop from 5 to 20 Hz (R5 - R20, kPa x s x L-1) was considered as an indirect index of resistance of the peripheral airways. The oscillometer was calibrated daily. | Change from Baseline R5-R20 at 12th week |