Closing Volume Interpretation and Bronchodilators Effect

Study Overview
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Brief Summary
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The gold standard measures to evaluate small airways (SAW) in vivo is not well understood Two tests are today used to measure SAW but real results concordance is not clear These problems have a small evidence Data about real effect of bronchodilators on SAW (eg Tiotropium and Indacaterol) has never been studied Only an acute bronchodilators effect, after one hour of drugs inhalation, will be evaluated The time frame of study evaluations per patient will be of three hours: one hour for basal test; one hour rest after drug administration; one hour for post bronchodilators test All enrolled subjects will be outpatients and will be evaluated after 24 hours of inhalatory drugs washout

Detailed Description
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Evaluation of small airways both in healthy and Chronic Obstructive Pulmonary Disease (COPD)subjects still today remains a big problem with implications in diagnostic and clinical management. The first lung alteration in smokers is the bronchiolitis and possibility to understand real damage on this anatomical district should be very interesting. The first point of the study will be the SAW evaluation. The two principal technics to do this are: Single Breath Test (SBT) and oesophageal balloon (EB). With SBT is possible to obtain the four expiration phases and so the shift from phase 3 to phase 4 identifying the point called closing capacity (CC). With EB is possible to obtain the lung static pressure-volume curve and after this to identify the point of closing volume (CV). The real concordance of CC and CV has never been studied both in healthy and COPD subjects. The SBT is performed by pneumotachograph matched with a gas analyzer. Patient breath normally for some seconds, exhales to residual volume (RV) and after that deeply inhales oxygen (100%) to total lung capacity (TLC), then the patient exhales slowly to RV. This test will be repeated a minimum of three times. The evaluation of CV will be performed by EB. The oesophageal balloon is introduced by nose and located in distal oesophageal tract. By pressure transducer the correct position will be confirmed. After the investigators will perform the evaluation of lung volume, trans pleural pressure and flow. These parameters will be registered at tidal volume, during forced expiration and finally during hyperventilation. So, after the identification of presence,absence and eventually concordance of CC and CV should be interesting to evaluate the possible effect on SAW of bronchodilators usually used in clinical practice. More in detail, the investigators will administered in random order and after basal evaluation of CV and CC dry powder of indacaterol 300 micrograms (mcg) or Tiotropium 18 mcg. After one hour of drug administration the investigators will repeat the maneuver for CC and CV evaluations. In this way, will be evaluated only the acute effect of the bronchodilators on lung hyperinflation. Each subjects will perform plethysmographic test too. Bronchodilators will be administered only to the COPD patients.

Official Title
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Small Airways Evaluation and Peripherical Effect of Two Bronchodilators in Healthy Subjects and Stable COPD Patients

Conditions
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Healthy, COPD

Intervention / Treatment
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* Drug: Indacaterol maleate
* Drug: Tiotropium bromide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signature of informed consent Healthy subjects with age from 20 to 80 yars old and never smokers COPD diagnosis COPD with age from 50 to 85 years old History of COPD at least of noe year Respiratory stable conditions at least of one month Any basal FEV1 expressed in % of predicted value FEV1/Forced Vital Capacity (FVC) less than 70% COPD with history of former or active smokers with minimum of 20 pack year Exclusion Criteria: Pregnancy FEV1/FVC more than 70% Known deficit of alpha 1 antitrypsin Subjects submitted to a Lung Volume Reduction Surgery (LVRS) Subjects with known positivity to Human Immunodeficiency Virus (HIV) Known intolerance to a nasogastric balloon Misuse of alcool or drugs Absence of compliance in performing respiratory test

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Indacaterol maleate<br>Indacaterol 300 mcg via Breezehaler Inhaler will be administered by a third independent investigator not involved in the performing of any of the tests decribed, following a randomization list | Drug: Indacaterol maleate<br>* Dry powder, 300 mcg, only one inhalation with 24 hours duration<br>* Other names: Onbrez, Hirobriz, Onbrize, Oslif Breezehaler, Arcapta;|
| Active Comparator: Tiotropium bromide<br>Tiotropium 18 mcg, via HandiHaler inhaler will be administered by a third independent investigator not involved in the performing of any of the tests decribed, following a randomization list | Drug: Tiotropium bromide<br>* Dry powder, 18 mcg, only one inhalation with 24 hours duration<br>* Other names: Spiriva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Closing Volume (CV) | The evaluation of CV will be performed by EB. The oesophageal balloon is introduced by nose and located in distal oesophageal tract. By pressure transducer the correct position will be confirmed. After the investigators will perform the evaluation of lung volume, trans pleural pressure and flow. These parameters will be registered at tidal volume, during forced expiration and finally during hyperventilation. | Participants will be followed for the duration of medical office stay an expected average of 3 hours. The outcome measure will be assessed for the end of october 2011 and will be presented within december 2011. | 
| Closing Capacity (CC) | The evaluation of CC will be measuired by Single Breath Test (SBT) and performed by pneumotachograph matched with a gas analyzer. Patient breath normally for some seconds, exhales to residual volume (RV) and after that deeply inhales oxygen (100%) to total lung capacity (TLC), then the patient exhales slowly to RV. This test will be repeated a minimum of three times. | Participants will be followed for the duration of medical office stay an expected average of 3 hours. The outcome measure will be assessed for the end of october 2011 and will be presented within december 2011 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Tiotropium or Indacaterol on CV and CC registration | Possible effect on small airways by two distinct ultra long acting bronchodilators | Participants will be followed for the duration of medical office stay an expected average of 3 hours. The outcome measure will be assessed for the end of october 2011 and will be presented within december 2011 | 
| Comparison concordance of CV and CC | This data will be important to identify the best, easiest and most reliable test for clinical SAW evaluation | Participants will be followed for the duration of medical office stay an expected average of 3 hours. The outcome measure will be assessed for the end of october 2011 and will be presented within december 2011 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Small Airways, Closing volume, Closing Capacity, Tiotropium, Indacaterol, COPD