IL MANAGEMENT RESPIRATORIO DEL PAZIENTE CON GLICOGENOSI 2 - Marco Confalonieri
S.C. Pneumologia
Azienda Ospedaliera-Universitaria
“Ospedali Riuniti di Trieste”
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Respiratory Management in Patients with Glycogenosis Type 2
1. IL MANAGEMENT
RESPIRATORIO
DEL PAZIENTE CON
GLICOGENOSI 2
Marco Confalonieri
S.C. Pneumologia
Azienda Ospedaliera-Universitaria
“Ospedali Riuniti di Trieste”
2.
3. 36,3
29,1
41,4
36,7
47,6 48,6
46,1
60
50
40
30
20
10
0
Età media (anni)
Insorgenza sintomi Diagnosi Supporto ventilazione Uso sedia a rotelle
Insorgenza tardiva (Mellies) n=20 Insorgenza tardiva (Hagemens) n=52
PRESENTAZIONE
CLINICA MALATTIA DI POMPE A INSORGENZA TARDIVA
STORIA NATURALE
Mellies U, Ragette R, Schwake C, et al. Sleep-disordered breathing and respiratory failure in acid maltase deficiency. Neurology. 2001;57:1290
1295.
Hageman M.L.C. Course of disability and respiratory function in untreated late-onset Pompe disease. Neurology 2006: 6 581-584
4. On average, adult patients with Pompe disease start mechanical
ventilation at the age of 50 years,which is 10 years later than the
average age of diagnosis. Combined with the finding that many
patients start mechanical ventilation during an episode of acute
respiratory failure,at diagnosis, patients should be referred to a
pulmonologist for regular evaluation and timely initiation of
respiratory aids when necessary, to avoid potentially
catastrophic situations during acute chest colds.
5. Respiratory involvement in juvenile and
adult glycogenosis type 2
• Respiratory symptoms as presenting
symptoms of Pompe’s disease (rare)
• Progressive ventilatory failure (common)
• Difficult expectoration
• Sleep-disordered breathing and nocturnal
respiratory failure
• Acute episodes (pneumonia)
• Bronchial asthma more frequent?
6. Cosa succede nella Malattia di Pompe ?
Muscoli respiratori:
- Muscoli respiratori
sempre compromessi
- Diafamma precocemente
colpito (*)
- La compromissione
respiratoria non è sempre
associata all'interessamento
muscolare generale
- Frequente riscontro in
corso di complicanze
infettive polmonari
Sivak ED, Salanga VD, Wilbourn AJ, Mitsumoto H, Golish J.
Adult-onset acid maltase deficiency presenting as
diaphragmatic paralysis. Ann Neurol 1981;9:613e5
(*)Hirschhorn R, Reuser AJJ. Glycogen storage disease
7. Interessamento muscoli respiratori
Nella late-onset:
- 60% dei casi lieve riduzione della
capacità vitale (CV) <80% ,
- 40% severa riduzione CV <60% *
- Talvolta esordio della malattia
con insufficienza respiratoria **
- Complicanze respiratorie
frequente casa di decesso
* Berger KI, Skrinar A, Norm0an RG, et al. Ventilatory
dysfunction in late onset pompe desease
** Keunen RW, Lambregts PC, Op de Coul AA, Joosten
EM. Respiratory failure as initial symptom of acid maltase
8. Quale è il sintomo principale?
Dispnea
Early onset:
Insorgenza a 1.6 mesi dalla nascita (*)
Insufficienza cardio-respiratoria
Late onset:
Sintomi inizialmente minimi per la grande riserva inspiratoria
(CV <50%) e mascherati dalla ridotta attività fisica
Talvolta all'esordio della malattia. (**)
* Kishnani PS,HwuP, Mandel H, Nicolino M, et al.Onbehalf of the Infantile Pompe natural history group. A retrospective, multinational, multicenter
study of the natural history of Infantile Pompe disease. J Pediatr 2006, in press.
** Keunen RW, Lambregts PC, Op de Coul AA, Joosten EM. Respiratory failure as initial symptom of acid maltase
9. Major Contributors to RF
in Acid Maltase Deficiency
• Progressive inspiratory muscle
weakness
• Depression of respiratory drive
• Expiratory muscle weakness leading to
ineffective cough and atelectasis
11. Prove di funzionalità respiratorie
Prove di funzionalità respiratoria:
Deficit restrittivo
Riduzione CPT
Aumento del VR
(dd altre malattie restrittive)
12. Deficit muscoli espiratori - tosse
Riduzione della pressione espiratoria muscolare MEP
Tosse inneficace (Picco della tosse < 160 l/min)255
Difficoltà di clearance secrezioni bronchiali
Infezioni
ricorrenti
13. Gabbia toracica – modificazioni struttura e
articolazioni
Deformità della gabbia toracica per debolezza
tronco e atrofia muscolare
Anchilosi delle articolazioni condrosternali e
costovertebrali per diminuita espansione
toracica (prevalentemente nella fase di
sviluppo)
Ridotta compliance gabbia toracica
14. Fatica muscolare e disfunzione della pompa
ventlatoria
P mus = R x V' + Vt / C
Pompa ventilatori non riesce a vincere la resistenze elastiche e di flusso
Forza muscolare Aumento resistenze
Ridotta compliance
Ridotto drive nervoso
Ridotto apporto
energetico
15. Disfunzione della pompa ventilatoria -
Ipoventilazione
Diminuzione del volume corrente
(Vt)
Vt = VA +
VD
All'inizio compensato dall'aumento della
frequenza respiratoria che porterà
ulteriore fatica muscolare e un aumento
dello spazio morto sul Vt
16. Come si modificana l'EGA?
L' aumento pCO2 (>45 mmHg) si accompagna sempre al calo della pO2 (<60
mmHg)
17. 3) Alte vie aeree - OSAS
Sospetto alterazioni del sonno?
CV < 60%
Aumento bicarbonati all'EGA (>4mmol/L), policitemia.
Sintomi: sonnolenza diurna, cefalea mattutina, insonnia, gasping
notturno.
Polisonnografia:
Ipoventilazione (inizialmente dursante la fase REM dove lavora
solo il diaframma)
Alterazione: prima fase NREM aumentata, ridotta la fase REM
Apnee centrali o ostruttive (attenzione a movimenti toracici ridotti)
18. 3) Le alte vie aeree nella malattia di Pompe
Muscoli della lingua precocemente coinvolti (anche in assenza di
sintomi) *
Muscoli facciali meno coinvolti
Alterazione del sonno (associano con CV < 50%)
OSAS **
Disfagia - (Early onset) ***
Afasia motoria
* Dubrovsky et al. 2011, Carlier et al. 2011
** Mellies U, Ragette R, Schwake C, Baethmann M, Voit T, Teschler H. Sleep-disordered
breathing and respiratory failure in acid maltase deficiency.
Neurology 2001;57:1290e5
*** Jones et al., 2010
19. Riassumendo
Problemi fisiopatologici respiratori nella Malattia di
Pompe
Muscoli
inspiratori
Muscoli
espiratori
SNC-motoneuroni
Alte vie
aeree
Ipoventilazione
notturna
Insufficienza
respiratoria
ipossiemica
ipercapnica
Deficit tosse
Complicanze
infettive polmonari
Ridotto drive
respiratori Disturbi del sonno
20.
21. Respiratory symptoms may be the presenting manifestation in Juvenile and adult Pompe’s disease,
but this occurs in very few cases: no more than 2% (probably they are late diagnosis)
22. Rate of progression of patients with late-onset
Pompe disease
16 pts followed for 16 years, only 1/3 showed a faster respiratory decline
A B
Disease duration (y) Disease duration (y)
van der Beek NAME, et al. Neuromuscular Dis. 2009;19:113-7.
120
110
100
90
80
70
60
50
40
20
20
10
0
VC(%)
MCR-sumscore
40
35
30
25
20
15
10
5
0
0 5 10 15 20 25 30 35 0 5 10 15 20 25 30 35
23. Monitoring of pulmonary function in Pompe disease: a muscle
disease with new therapeutic perspectives
0 20 40 60 80 100
FVC Supine (% predicted)
PCO2 (mmHg)
van der Ploeg AT, et al. Eur Respir J. 2005;26:984-5.
55
50
45
40
35
30
24.
25. Respiratory Muscle Weakness
Associated with Ventilator Use
Spontaneous
breathing
CPAP Bilevel ventilation
100%
80%
60%
40%
20%
0%
Inspiratory Muscle Pressure
Expiratory Muscle Pressure
Nocturnal Ventilatory Therapy
Max Respiratory Pressure
% predicted
Mellies U, et al. Curr Opin Neurol 2005;18:543
26. Respiratory failure in Pompe disease: treatment with
non-invasive ventilation
B
before N/V
after N/V
Mellies U, et al. Neurology 2005;64:1465-7.
Mean nocturnal SaO2%
100
90
80
70
60
50
40
PaCO2 mmHg
110
100
90
80
70
60
50
40
30
Nadir nocturnal SaO2%
100
90
80
70
60
50
40
PaO2 mmHg
110
100
90
80
70
60
50
40
30
A
before N/V
after N/V
C D
50
40
30
before N/V
before N/V
after N/V
after N/V
27. NIV TO IMPROVE QUALITY OF LIFE IN POMPE’S
DISEASE
The administration of NPPV to glycogenosis type
II patients with chronic respiratory failure may be
expected to improve physiologic lung function and
quality of life (QoL), as well as decrease the frequency
of episodes requiring acute care facilities.
Bembi B, et al. Neurology 2008; 71(Suppl 2): s12-s36
Hagemans ML, et al.. Neurology 2006; 66:581–583.
28.
29.
30.
31.
32.
33.
34. Conclusion
• In this study population, treatment
with alglucosidase alfa was
associated with improved walking
distance and stabilization of
pulmonary function over an 18-
month period
35.
36.
37.
38.
39. • Of 13 patients requiring ventilatory support at baseline (4 tracheostomized,
9 mask-ventilated), 3 patients recovered from tracheostomy (1 juvenile, 2
adults) and 2 completely interrupted ventilation support: a tracheostomized
adolescent girl and an adult female requiring daily mask ventilation.The
other patients reduced median daily ventilation from 14 to 8h atT12(p =
0.0005).These results were maintained throughout the follow-up to T3.
42. Respiratory acute episodes and
mortality
The most frequent cause of mortality
among juvenile or adult patients affected
with the form of Pompe disease is
respiratory failure.
Death may be due to pneumonia and/or
respiratory muscle fatigue and failure.
43. Pneumonia in juvenile and adult
glycogenosis type 2
These are very dangerous episodes during
life history of patients affected by
Pompe’s disease.
Intubation and tracheostomy are common
Life-treathening complications are possible
(sepsis, ARDS, MOFS)
44. Aggressive treatment of acute
respiratory failure
• Noninvasive ventilation
• Early respiratory rehabilitation
• Closure of tracheostomy if possible
• ERT
• Cough assistance
• Chest physical therapy
• Mini-trach
46. Respiratory monitoring and
rehabilitation
• At least every year lung function tests
• Regular PaCO2 assessment
• Sleep study
• Respiratory rehabilitation + ERT + diet
• Regular use of Threshold for diaphragm
and inspiratory muscles training
48. LE GLICOGENOSI di tipo II° o MALATTIA di
POMPE
RIALLENAMENTO DELLA MUSCOLATURA
RESPIRATORIA
OBIETTIVI
• Incremento della funzionalità respiratoria
• Miglioramento dei dati di laboratorio
• Miglioramento della tolleranza allo sforzo
• Riduzione della ventilazione meccanica
49. LE GLICOGENOSI di tipo II° o MALATTIA di
POMPE
Trattamento attuale con Threshold
50.
51. Asthma in Pompe’s disease
• More of 50% of our case series patients
have bronchial asthma (someone allergic
asthma)
• There is a link between prevalence of
asthma and glycogenosis?
• When recognized asthma should be
treated
• Response to antiasmathic therapy is good
and improve respiratory symptoms