Mécanismes de la dyspnée dans la BPCO

Transcription

1 Module dyspnée DES de pneumologie Mécanismes de la dyspnée dans la BPCO Dr. Pierantonio Laveneziana Service d Explorations Fonctionnelles de la Respiration, de l'exercice et de la Dyspnée (EFRED) Département "R3S" (Respiration, Réanimation, Réhabilitation, Sommeil) Groupe Hospitalier Pitié-Salpêtrière Charles Foix Assistance Publique-Hôpitaux de Paris Sorbonne Universités, UMR_S 1158, INSERM et Université Pierre et Marie Curie (Paris 6) Neurophysiologie Respiratoire Expérimentale et Clinique

2 Exacerbations Co-morbidities Inflammation Poor quality of life Degree of airflow obstruction (FEV 1 ) COPD Gas exchange abnormalities Ventilatory Limitation and Mechanical constraints Breathlessness Anxiety Depression Exercise intolerance Poor nutritional status Cardiovascular limitation Peripheral muscle dysfunction/weakness Laveneziana P and Palange P, Eur Respir J. 2012

3 Dyspnée: "un inconfort respiratoire survenant pour un niveau d'activité usuel qui n'entraîne normalement aucune gêne [Killian et Campbell, 1991]. Cette définition permet de dire que la dyspnée est d'autant plus sévère que l'intensité de l'activité qui la provoque est faible [Killian et Campbell, 1991]. Laviolette L and Laveneziana P, Eur Respir J. 2014

4 Physical Task Ventilation Expiratory Flow Limitation Hyperinflation Rspiratory muscle weakness/fatigue/dysfunction DYSPNOEA Deconditioning Peripheral muscle dysfunction/weakness Physical Activity Poor health-related quality of life Laviolette L and Laveneziana P, Eur Respir J. 2014

5 Normal COPD P L V. P L V. expiratory flow-limitation airways resistance airway tethering Expiratory flow-limitation mechanical time-constant for lung emptying (compliance x resistance) Expiratory time available is insufficient to allow EELV to return to its baseline value Gas retention or air trapping or lung hyperinflation Laviolette L and Laveneziana P, Eur Respir J. 2014

6 Normal COPD P L V. P L V. expiratory flow-limitation airways resistance airway tethering In other words, lung emptying during expiration becomes incomplete because it is interrupted by the next inspiration and EELV therefore exceeds the natural relaxation volume of the respiratory system (Palv > Patm) Laviolette L and Laveneziana P, Eur Respir J. 2014

7 Dynamic hyperinflation: a temporary and variable increase in end expiratory lung volume (EELV) beyond its baseline value EELV: volume of gas left in the lung at the end of a quiet breath out Laviolette L and Laveneziana P, Eur Respir J. 2014

8 Ventilatory Mechanics: Healthy Expiration Inspiration Flow (L/s) TLC 8 6 EELV 4 RV IRV V T ERV IC Volume (L)

9 Ventilatory Mechanics: Healthy Expiration Inspiration Flow (L/s) TLC 8 6 EELV 4 2 IRV V T RV 0-2 ERV IC Volume (L)

10 Ventilatory Mechanics: Healthy Volume (liters) 8 6 EILV TLC IRV IC 4 V T 2 EELV EELV 0 RV Pressure (cmh 2 0)

11 Ventilatory Mechanics: Healthy S Raw (cmh 2 O/L/sec) % VC 100 ΔP = ΔV ΔP = ΔV elastic WOB 4 RV elastic and resistive work of breathing is minimized when tidal breathing occurs 3 within the compliant portion of the respiratory systems 2 P-V curve 20 ΔP = ΔV 1 TLC Pressure (cmh 2 O) resistive WOB Lung Volume (liters) S Raw as lung volume because the airways distend as the lungs inflate, and bigger airways have lower resistance (*Poiseuilles Law*). The opposite is also true, of course!

12 Ventilatory Mechanics: COPD Older Male Age = 66 yrs Mild COPD Age = 67 yrs Severe COPD Age = 65 yrs EF reserve!!! no EF reserve!!! 2 EELV EELV EELV EELV EELV EELV Volume (L) Volume (L) Volume (L) 3 2 Laveneziana P, et al. Appl. Physiol. Nutr. Metab. 2007; 32:

13 Ventilatory Mechanics: COPD Lung Volume (% pred TLC) 150 TLC ΔP = ΔV IC 100 EELV 50 When V T occurs at high lung volumes: elastic WOB Pressure(cmH 2 O)

14 Ventilatory Mechanics: COPD P sniff Lung hyperinflation (static and/or dynamic EELV increase) places the inspiratory muscles, especially the diaphragm, at a significant mechanical disadvantage by shortening its fibers, thereby compromising its force generating capacity [Laghi F and Tobin MJ. Am J Respir Crit Care Med 2003; 168: 10-48] reserve In the presence of static lung hyperinflation this functional muscle weakness is mitigated, to some extent, by long term adaptations which causes a leftward shift of the length-tension relationship, thus improving the ability of the muscles to generate force at higher lung volumes: shortening of diaphragmatic sarcomeres [Orozco- Levi M, et al. Eur Respir J 1999; 13: ] decrease in sarcomere number [Supinski GS, Kelsen SG. Effect of elastase-induced emphysema on the force-generating ability of the diaphragm. J Clin Invest 1982; 70: ]

15 Ventilatory Mechanics: COPD P sniff In patients with chronic lung hyperinflation, adaptive alterations in muscle fiber composition (an increase in the relative proportion of slow-twitch, fatigue resistant, type I fibres) [Levine S, et al. N Engl J Med 1997; 337: ; Mercadier JJ, et al. Am J Physiol 1998; 274(4 Pt 1): L ] reserve and oxidative capacity (an increase in mitochondrial concentration and efficiency of the electron transport chain) [Orozco-Levi M, et al. Eur Respir J 1999; 13: ] are believed to preserve the functional strength of the overburdened diaphragm [Similowski T, et al. N Engl J Med 1991; 325: ] and make it more resistant to fatigue [Orozco-Levi M, et al. Eur Respir J 1999; 13: ; Levine S, et al. N Engl J Med 1997; 337: ; Mador MJ, et al. Am J Respir Crit Care Med 2000; 161: ]

16 Ventilatory Mechanics: COPD %VC In this regard, Similowski and colleagues demonstrated that the reduction in pressure-generating capacity of the inspiratory muscles of stable COPD patients was related to lung hyperinflation and that diaphragmatic function in such patients was comparable to normal subjects when measurements were compared at the same lung volume Similowski T, et al. N Engl J Med 1991; 325: The evidence that measurable fatigue develops in COPD is inconclusive, even at the limits of tolerance Pressure (cmh 2 O) Mador MJ et al., Am J Respir Crit Care Med 2000; 161: Bye PT et al., Am Rev Respir Dis 1985; 132: Sinderby C et al., Am J Respir Crit Care Med 2001; 163: Polkey MI et al. Am J Respir Crit Care Med 1995; 152:

17 Negative effects of DH during exercise Elastic/threshold loads Inspiratory muscle weakness Reduced V T expansion tachypnea Pes/PImax effort C L dyn V D /V T PaCO 2 Early ventilatory limitation to exercise Cardiac impairment Exertional dyspnoea

18 Nneuromechanical coupling in healthy during exercise O Donnell et al, Proc Am Thorac Soc 2007

19 pulmonary (vagal) afferent activity Corollary discharge 3 limbic system somatosensory cortex motor cortex? Respiratory distress? Dyspnea brainstem 1 Ventilatory drive Respiratory mechanics 2 Neuromechanical dissociation airways lungs muscles

20 Lung volume (L) Exertional Dyspnoea in COPD during exercise TLC IRV V T IC Exercise time (min) Laveneziana P et al, AJRCCM 2011

21 Exertional Dyspnoea in COPD during exercise V T inflection V T inflection work/effort unsatisfied inspiration Dyspnoea P oes /P sniff, P oes /V T V E, EELV, etc. work/effort unsatisfied inspiration V T inflection Laveneziana P et al, AJRCCM 2011

22 Descriptor (% of subjects) Descriptor (% of subjects) A B 100 INCR exercise Effort IN OUT Inspiratory difficulty Unsatisfied inspiration 40 Work 20 Rapid Expiratory difficulty Exercise time (min) Heavy INCR 100 CWR exercise Hunger CWR Shallow Suffocating Tight Selection Frequency (% of subjects) Exercise time (min) Laveneziana P et al, AJRCCM 2011

23 Interaction between muscle fatigue and dyspnoea in COPD Does leg fatigue influence the perception of dyspnoea in exercising patients with COPD? Laviolette L and Laveneziana P, Eur Respir J. 2014

24 Central motor output Group III and IV muscle afferents Adapted from Dempsey JA et al. Respir Physiol Neurobiol 2006;151:

25 Fatigue protocol Gagnon et al. JAP 2009;107:

26 Force loss (%) Pre-induced fatigue and exercise tolerance 0 MVC TwQ CONTROLS COPD * CONTROLS COPD -30 * * -40 * -50 Gagnon et al. JAP 2009;107:

27 Endurance Time (sec) Pre-induced fatigue and exercise tolerance 600 * * CONTROLS COPD Gagnon et al. JAP 2009;107:

28 Pre-induced fatigue and exercise tolerance Gagnon et al. JAP 2009;107:

29 Spinal anesthesia Anesthesia Fentanyl (intrathecal) [25 g ] Placebo (NaCl) Injection (L2/L3)

30 Spinal anesthesia and exercise tolerance Gagnon P et al. AJRCCM 2012;186:

31 Spinal anesthesia and exercise tolerance Gagnon P et al. AJRCCM 2012;186:

32 Spinal anesthesia and exercise tolerance Gagnon P et al. AJRCCM 2012;186:

33 Interpretation Spinal anesthesia improved exercise tolerance in COPD. As a result of spinal anesthesia, the perception of leg fatigue was decreased, central motor output was increased and the degree of fatigue increased. The reduction in VE was important in explaining the improved exercise tolerance and reduction in dyspnea with spinal anesthesia.

34 Lactic acid (mmol/l) Lactate kinetics COPD Controls VO 2 (L/min) Maltais et al. AJRCCM 1996;154:142-7.

35 Peripheral and central components of exercise limitation Metabolic changes lactate premature acidosis Afferent stimulation Ventilation dypnoea Casaburi. Principles and practice of pulmonary rehabilitation, 1993.

36 Leg fatigue? Dyspnoea Perturbation in limb muscle energy metabolism with enhanced lactate production may directly stimulate ventilation and as such increased dyspnoea perception. Leg fatigue may increase signalisation through group III/IV afferents. This in turn may increase dyspnoea perception via ventilation-dependant and independent mechanisms.

37 Mechanisms of action Casaburi and Zuwallack NEJM 2009;360:

38 Ventilation Exercise to reduce ventilatory requirements Better muscle function lactate less acidosis afferent stimulation ventilation Activity level Ventilatory limitation Ventilatory requirements Casaburi. Principles and practice of pulmonary rehabilitation, 1993.

39 Dyspnoea in COPD Drive [H+] CO 2 O 2 SNS activity Muscle afferents Mechanics/Muscles Higher Centres Restriction Anxiety IRV, VT Distress Dynamic mechanics CLdyn Elastic/ITL loads PImax Fatigue Accessory muscle use Laviolette L and Laveneziana P, Eur Respir J. 2014

40 Putative neurophysiological basis of exertional dyspnoea CENTRAL (Corollary Discharge): motor drive (inspiratory effort) cortical reflexic drive (chemical, neural) - medullary PERIPHERAL (Afferent Activity): Airway/lung receptors (pulmonary stretch receptors, C-fibres, J-receptors) Ventilatory muscle receptors (muscle spindles, Golgi tendon organs, joint receptors, type III and IV mechano- and metabo-receptors in the diaphragm and chest wall muscles) Peripheral chemoreceptors Locomotor muscles receptors (type III and IV afferents) Laviolette L and Laveneziana P, Eur Respir J. 2014

41 pulmonary afferent activity (vagal, phrenic, spinal) Corollary discharge Anxiolytics motor cortex limbic system? Respiratory distress somatosensory cortex Dyspnea? Opiates brainstem Oxygen Ventilatory drive Respiratory mechanics Neuromechanical dissociation Bronchodilators helium airways Antiinflammatory lungs muscles