OBESI’TA ED ASM A - Medici Groane · The leptin/leptin receptor pathway is involved in lung...
Transcript of OBESI’TA ED ASM A - Medici Groane · The leptin/leptin receptor pathway is involved in lung...
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’OBESITA ED ASMA
Dott. Stefano Spagnotto U O Pneumologia GarbagnateU.O.Pneumologia Garbagnate Milanese 20.03.2010
Associazionecas ale ocasuale o causale?
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Over 33 million people a year die from chronic (noncommunicable) diseases, including cardiovascular
disease, cancers, diabetes and chronic respiratory diseases
WHO Surveillance of Risk Factors Report Series (SuRF)p ( )
1. tobacco use
2. excessive alcohol consumption
3. low fruit and vegetable intake
4. obesity
5. raised blood pressure
6. raised cholesterol
7. physical inactivity
8. diabetes.
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BMI = peso KG / (statura m )²
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EPIDEMIOLOGIA SOVRAPPESO EPIDEMIOLOGIA OBESITA’
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Overweight, Obesity, and Incident AsthmaA Meta-analysis of Prospective Epidemiologic StudiesDavid A. Beuther and E. Rand SutherlandAm J Respir Crit Care 2007
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Studi Epidemiologici (>1500)Cross-sectional and case-controlled studies (40 studies)Obesity as BMI: overweight (25 kg/m2– 29.9 kg/m2) and
obese (>30 kg/m2) B th S th l d A J R i C it C M d 2007obese (>30 kg/m2) Beuther,Sutherland: Am J Respir Crit Care Med 2007
La presenza di errori (bias) grossolani come il peso dichiarato i sintomi dichiarati i criteri sul consumo di dichiarato, i sintomi dichiarati, i criteri sul consumo di farmaci,il mancato utilizzo della spirometria o della BHR, la dispnea intesa come asma,hanno fatto BHR, la dispnea intesa come asma,hanno fatto escludere un numero altissimo di studi
Presenza di variabili confondenti : stato Presenza di variabili confondenti : stato socioeconomico, attività fisica, dieta, età, fumo
Correlazione modesta tra obesità e prevalenza Correlazione modesta tra obesità e prevalenza dell’asma negli adulti, con rischio relativo o odds ratios compreso tra 1.0 to 3.0 (> nelle donne) ratios compreso tra 1.0 to 3.0 ( nelle donne) (addirittura qualche dato sulla forma J della distribuzione della prevalenza dell’asma)
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EpidemiologiaEpidemiologiaStudi Prospettici
Meta-analisi di 7 studi epidemiologici tti i i ti d l l i prospettici mirati a sondare la relazione asma-
obesità
Obesità deve precedere l’asma
E d i t b bilità di il End point: probabilità di sviluppare asma dopo un anno di osservazione
Beuther DA, Sutherland ER. Overweight, obesity and incident asthma: a meta-analysis of prospective epidemiologic studies. Am J Respir Crit Care Med 2007;175:661–6.
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id d ll’Incidenza dell’asma aumenta del 50%
li i di id inegli individui obesi/sovrappeso.
Am J Respir Crit Care Med Vol 175. pp 661–666, 2007
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Conclusions: Children with high body weight, either at birth or later in childhood, are at increased risk for future asthma (1.5 infanzia, 1.2 alla nascita)
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OBESITA’ ED ASMAOBESITA ED ASMA
• Motivi “meccanici o geometrici” legati alla
• Motivi “metabolici” legati alla complessa
modificazione dell’apparato
interdipendenza della “malattia obesità” con
respiratorio indotta dall’accumulo adiposo
l’organismo (apparato respiratorio,
addominale e nelle fasce toraciche
cardiovascolare, ecc)
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Principali modificazioni polmonari nell’obeso
A t l i tti ità• Diminuisce CFR, CPT,VREA t R i t
• Aumenta la iper-reattività bronchiale (BHR)
• Diminuisce la plasticità• Aumento Resistenze• Diminusce Forza mm.
Respiratori
Diminuisce la plasticità dei muscoli bronchiali
• Mancanza del riflesso Respiratori• Aumenta la rigidità della
gabbia toracica
broncodilatatore indotto dalla inspirazione profondagabbia toracica profonda
• Precoce disaccoppiamento drive pprespiratorio/ventilazione = DISPNEA
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fisiopatologia
I legami actina-mosina tendono ad
iù fi i essere più fissi e meno instabili
Obesity and Asthma, Am J Respir Crit Care Med 2006 ; 174. 112–119,
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Effetto dell’obesità sui volumi polmonariEffetto dell obesità sui volumi polmonari
Sin, D D et al. Thorax 2008;63:1018-1023
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Lavoro respiratorioLavoro respiratorio
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normale
enfisemaenfisema
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normale
Obesita’Obesita
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Effect of lung volume on airway resistanceEffect of lung volume on airway resistancem
eg
Volu
mLu
ng
Airwaycaliber
Raw
caliber
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Effect of lung volume on airway resistanceEffect of lung volume on airway resistancem
eg
Volu
mLu
ng
Airwaycaliber
Raw
caliber
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Airway conductance (Gaw) by increasing BMI
Males n 139 Females n 137Males n=139 Females n=137
King GG et al. - Eur Respir J 2005; 25: 896–901
Airways were narrower than expected on the basis of the reduction in y plung volume, suggesting that there were structural or functional
changes in the airways that were specifically associated with increasing body mass index.body mass index.
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Evidenze che fattori geometrici aumentino la BHR negli ObesiBHR negli Obesi
Airway responsiveness in obese nonasthmatic subjects
r2 = 0.32, p< 0.001
Solid and open pcircles identify men and women, respectively
Torchio R et al. J Appl Physiol 107: 408–416, 2009.
respectively.
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Airway responsiveness in obese Evidenze che fattori geometrici aumentino la
BHR negli Obesinonasthmatic subjects (men)
BHR negli ObesiAirway responsiveness in obese nonasthmatic subjects
r2= 0.56, p< 0.001
Torchio R et al. J Appl Physiol 107: 408–416, 2009.
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Bronchodilation and Bronchoprotection by Deep Inspiration end Their Relationship to Bronchial HyperresposivenessTheir Relationship to Bronchial HyperresposivenessG. Skloot A. Togias Clinical Reviews in Allergy and immunology 2003
Mancanza riflesso broncodilatatore legato all’inspirazione profonda nei saniMancanza riflesso broncodilatatore legato all inspirazione profonda nei sani
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Anche l’attività fisica influenza la reattività bronchiale
in modo proporzionale inverso
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Diminuzione della plasticità muscoli bronchialiObesity and airway function
Obesity leads to decrements in functional residual capacity (FRC) andObesity leads to decrements in functional residual capacity (FRC) and tidal volumes (VT), resulting in dynamic decreases in smooth muscle stretch. The resultant latching of the smooth muscle leads to enhanced airways reactivity and irreversibility of obstruction. These effects may y y y ybe enhanced by breathing around the closing volume, which is characteristic of morbid obesity
Tantisira KG, Weiss S. Thorax 2001
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•Ipoventilazione
•Ostruzione bronchiale•Ostruzione bronchiale
•Instabilità bronchiale
Rid i d ll f li •Riduzione della forza muscoli resp.
Precoce disaccoppiamento D i Drive
respiratorio/ventilazione = DISPNEADISPNEA
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Queste modificazioni interessano inoltre per…..
• OSAS Sindrome Apnee Notturne (macroglossia, ( g ,retrognazia, ipertrofia delle pareti ipofaringe e laringe)pareti ipofaringe e laringe)
• OHS Sindrome obesità ( 30ipoventilazione (BMI>30,
paCO2>45,assenza di paltre malattie respiratorie)
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OBESITA’ ED ASMAOBESITA ED ASMA
• Motivi “meccanici o geometrici” legati alla
• Motivi “metabolici” legati alla complessa
modificazione dell’apparato
interdipendenza della “malattia obesità” con
respiratorio l’organismo (apparato respiratorio, cardiovascolare, ecc)
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Effetto Effetto proinfiammatorio
Aritmie
SCC
Ernia iatale GER SCCGER
Effetto I i ♀♂ Effetto protrombotico
TVP TEP
Iperestrogenismo ♀♂
Iperandrogenismo ♀
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Mancuso P - JAP 2009
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Sazietà (Oressine) diminuisce lipogenesi, aumenta lipolisi e spesa energetica
ti l
e spesa energetica
alta
stimolanoInfezioni
TNF, interleukina
LEPTINA(adipociti)
1
( p )
bassaInibiscono:Adrenalina
T3, GH
Sistema immunitario
DigiunoBassi livelli
insulina ipotalamo-ipofisi-gonadiinsulina
fame
ipotalamo ipofisi gonadiipotalamo-ipofisi-surreneipotalamo-ipofisi-tiroide
fame
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Relationship between serum Relationship between serum adipokines and asthma
Lugogo NL et al. – JAP 2009
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Leptin and leptin receptor are expressed b b hi l ith li l ll (16HBE)by bronchial epithelial cells (16HBE)
Leptin receptorLeptin Leptin receptorLeptin
The leptin/leptin receptor pathway is involved in lung epithelial homeostasis in asthma. Its expression decreases in subjects with uncontrolled and severe asthma and is in ersel correlated ith air a remodeling
A Bruno et al 2009
inversely correlated with airway remodeling.
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Obesity is a state of
chronic low grade systemic inflammationinflammation.
The current paradigmis that inflammation
Leptin, IL-6TNF-alfa, TGF-beta
Eotaxin, CRPspills over into the blood, leading to
inflammatory activationat sites distant to the
adipose tissue.
( Beuther et al. Am J Resp Crit Care Med 2006; 174:112 ; with modifications)
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Obesità ed effetti sistemici mediati da ormoni e citokine
Physical Inactivity and Obesity N.H.T.ten Hacken 2009
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Candidate genes of potential relevance to both obesity and asthma
Beuther DA et al. - Am J Respir Crit Care Med Vol 174:112–119; 2006
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Gene (Human Genome
Position Variant associated with
Variant associated withOrganization name) associated with
asthma-related phenotypes
associated with obesity-related
h tphenotypesTNF-α, TNF 6p21.3 308-G/A 308-G/A
Eur Respir J,May 2009
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Cluster Analysis and Clinical Asthma Phenotypes AJRCCM 2008
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Obesity-Asthma Phenotypey ypSintomi persistenti
Tempi di ricovero più lunghi anche in UTI Tempi di ricovero più lunghi anche in UTI
Riduzione della qualità di vita
Mi t ll d ll’Minor controllo dell’asma
Aumento delle ospedalizzazioni per asma
Alterata risposta alle terapie
Prevalenza femminile, scarsa atopia
Asma più severa oppure asma più difficile per la prevalenza maggiore di altre comorbidità fisiche e prevalenza maggiore di altre comorbidità fisiche e
psicologiche?
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La prova del 9La prova del 9
Se a forza di correre…..
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• Weight reduction significantly improved g y pFEV1, FVC, and health status in obese people
ith thwith asthma.• The number of asthma
exacerbations andexacerbations and courses of oral steroids could also be reducedcould also be reduced
BMJ 2000.
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Surgically induced weight lloss
1. Murr et al., 1995;1. Murr et al., 1995;
2. Dixon et al., 1999;
3. Dhabuwala et al., 2000 ;
4. Dixon and O’Brien, 2002; These studies report
significant 5. O’Brien et al., 2002;
6 H d St bb 2004
gimprovements in all asthma outcomes,
6. He and Stubbs, 2004;
7. Simard et al., 2004;
,including prevalence,
severity , use of asthma 8. Ahroni et al., 2005;
9 Spivak et al 2005
y ,medications, and hospitalizations9. Spivak et al., 2005. p
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Grazie per l’attenzione.