M Barnes P J N Engl J Med
Mηχανισμοί απόφραξης Barnes, P. J. N Engl J Med 2000; 343: 269 -280
Static hyperinflation
Reduced expiratory flow rate, destruction of alveoli, and short exhalation time lead to… Hyperinflation Increased A-P Diameter Low, Flattened Diaphragm Air Trapping
VT IRV Dynamic versus static hyperinflation Respiratory frequency: 15/min Respiratory frequency: 30/min Healthy Subject VT Severe COPD ERV Trapped volume at 30/min. Trapped volume at 15/min end expiration Vt - Tidal Volume; IRV - Inspiratory Reserve Volume; ERV - Expiratory Reserve Volume.
Dynamic hyperinflation during exacerbation IC IRV VC TLC IC IC IC TV ERV FRC RV Bronchospasm + increasing respiratory frequency: increasing flow limitation, less time for expiration RV - Residual Volume; VC – Vital Capacity; TV - Tidal Volume; IRV - Inspiratory Reserve Volume; ERV - Expiratory Reserve Volume; IC - Inspiratory Capacity; FRC - Functional Residual Capacity; TLC - Total Lung Capacity. Modified from N Tzanakis
Pathophysiological Features of Airflow Obstruction in Chronic Obstructive Pulmonary Disease (COPD) Niewoehner. N Engl J Med. 2010 Apr 15; 362(15): 1407 -16.
ΧΑΠ: Δυναμική υπερδιάταση REST EXERCISE IC Volume IC G H F PEEPi work D EELV E B FRC C Dynamic hyperinflation A Passive FRC Τροποποιημένα από Ν. Τζανάκη 0 Pressure + PEEPi
600 ml PEEPi 600 ml
Hyperinflation and the diaphragm
Limitación de flujo y de Volumen.
Flow Pes W elastic P-V curve W resistive reduction bronchial caliber W PEEPi
Myosin
Force ~ number of myosin heads attached to actin
600 ml PEEPi 600 ml
Hyperinflation
PEEPi detection
flow Flow Waveform inhalation time 0 auto-PEEP exhalation
Pplateau VT PEEPi Hyperinflation
No active exhalation or inspiratory effort Treats lungs as single compartment PIP pressure PIP auto PEEP set PEEP time
PEEPi, st=8
auto-PEEP of 5 cm H 2 O by occlusion technique Leatherman, Crit Care Med 1996; 24: 541
IMPROVEMENT IN RESTING IC AND HYPERINFLATION WITH TIOTROPIUM IN COPD PATIENTS WITH INCREASED STATIC Διαφορά (T – P) την ημέρα 28 (m. L) VOLUMES Προ 600 ** ** ** 400 200 Μετά ** ** ** 0 -200 -400 -600 -800 * FEV 1 FVC Ροή *P<0. 01, **P<0. 001 versus placebo IC ** FRC Όγκοι Celli et al. Chest 2003; 124: 1743 -1748.
Indacaterol (150 μg) reduces Hyperinflation IC – Inspiratory capacity. Rossi et al. Respir Med. 2012 Jan; 106(1): 84 -90.
Indacaterol (150 μg) reduces hyperinflation FRC - Functional Residual Capacity; TLC - total lung capacity; RV - residual volume. Rossi et al. Respir Med. 2012 Jan; 106(1): 84 -90.
placebo -- - - έναρξη 42 ημέρες Τιοτρόπιο O’Donnell et al. ERJ 2004; 23: 832 -40
Inspiratory Capacity at end exercise End-exercise IC (L) 190 m. L* IC - Inspiratory Capacity. 280 m. L** 2. 22 2. 17 1. 98 1. 94 Data are least squares means and standard error. *p=0. 04; **p=0. 002. O'Donnell et al. Respir Med. 2011 Jul; 105(7): 1030 -6.
Mechanisms of improved exercise tolerance in COPD in response to tiotropium Placebo (n=91) Tiotropium (n=96) Χρόνος ανοχής (sec) 11 ** * 10 =1 min 45 s =1 min 7 s (21. 4%) (13. 6%) 9 8 min 12 s 8 -5 0 5 10 15 20 25 30 35 40 45 Ημέρα Baseline *P<0. 05, **P<0. 01 O’Donnell et al. ERJ 2004
Indacaterol increases exercise time 101 s*** 111 s* Time (seconds) 585 484 586 475 Data are least squares means and standard error. *p=0. 011; ***p<0. 001. O'Donnell et al. Respir Med. 2011 Jul; 105(7): 1030 -6.
Ολοδατερόλη/Τιοτρόπιο: Μείωση υπερδιάτασης (FRC και RV) στις 6 εβδομάδες και πολλές ώρες μετά τη δόση FRC and RV at Week 6 200 100 FRC 2: 30 post-dose FRC 22: 30 post-dose RV 22: 30 post-dose -100 -200 * -300 * -400 -500 -600 * -700 -800 Placebo (n=86) Tiotropium+Olodaterol 5/5μg FDC (n=93) * Olodaterol 5 µg (n=90) Tiotropium 5 µg (n=94) *p<0. 05 for Tiotropium+Olodaterol 5/5μg FDC vs placebo and all tiotropium or olodaterol monotherapies FRC was measured using body plethysmography in a subset of 143 patients after 6 weeks of treatment Beeh KM, et al. Pulmonary Pharmacology & Therapeutics 2015; 1 -7. Improvement Response (m. L) 0
Hyperinflation Bronchodilators
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