Closing Volume Interpretation and Bronchodilators Effect
Condition: Healthy; COPD
Study type: Interventional
Phase: Phase 4

Summary: 
      -  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: 
      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.
    

Intervention name(s): Indacaterol maleate; Tiotropium bromide
Intervention type(s): Drug; Drug
Intervention description(s): Dry powder, 300 mcg, only one inhalation with 24 hours duration; Dry powder, 18 mcg, only one inhalation with 24 hours duration
Other intervention name(s): Onbrez, Hirobriz, Onbrize, Oslif Breezehaler, Arcapta; Spiriva
Intervention MeSH terms: Bromides; Tiotropium Bromide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Small Airways; Closing volume; Closing Capacity; Tiotropium; Indacaterol; COPD