Pulmonary Involvement in Obesity

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ภาคว ชากมารเวชศาสตร� คณะแพทยศาสตร�ศ ร ราชพยาบาล

Definition of ObesityDefinition of Obesity(body mass index)(body mass index)

BMI = weight (kg)/ height(m)BMI = weight (kg)/ height(m)22

WHO classification of adult categories of BMIWHO classification of adult categories of BMI

ClassificationClassification BMI (kg/mBMI (kg/m22))

UnderweightUnderweight <18.5<18.5

Normal rangeNormal range 18.5-24.918.5-24.9

OverweightOverweight

(pre-obese)(pre-obese)25-29.925-29.9

ObeseObese 3030

BMI (kg/mBMI (kg/m22))

<18.5<18.5

18.5-22.918.5-22.9

23-24.923-24.9

2525

CaucasianCaucasian AsiaAsia

Criteria and classification of obesity in Japan and Asia-OceaniaAsia Pacific J Clin Nutr (2002) 11(Suppl): S732–S737

Definition of ObesityDefinition of Obesity

ChildrenChildren

BMI percentileBMI percentile

> 5th and < 85th = normal weight for > 5th and < 85th = normal weight for heightheight

≥ ≥ 85th and < 95th = at risk for overweight85th and < 95th = at risk for overweight

≥ ≥ 95th = obese95th = obese

Weight for heightWeight for height

≥≥ 120th percentile = obesity120th percentile = obesity

≥ ≥ 110th percentile < 120 110th percentile < 120 = overweight = overweight

Children’s ages (in years) Australia:2–18, Brazil: 6–18, Canada: 7–13,China: 6–18, Spain: 6–14, UK: 7–11, USA: 6–18.

The International Association for the Study of Obesity. obesity reviews 5 (Suppl. 1), 4–85

Trends in the prevalence of overweight

0

2

4

6

8

10

เด็�กปฐมวัย เด็�กวัยเรี�ยน

พ.ศ. 2539-2540 พ.ศ. 2544%

36%

15.5%

5.8 7.9 6.75.8

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Prevalence of obesity in Thai Prevalence of obesity in Thai childrenchildren

การส ารวจโรงเร(ยน การส ารวจโรงเร(ยน 342 342 โรงขอุงเคร)อุข*ายว จ!ยสขภาพ โรงขอุงเคร)อุข*ายว จ!ยสขภาพ ม+ลน ธิ สาธิารณสขแห*งชาต พ ม+ลน ธิ สาธิารณสขแห*งชาต พ..ศศ. 2548 . 2548 พบว*าพบว*า

อุ,วน ร,อุยละ อุ,วน ร,อุยละ 12 12 ท,วม ร,อุยละ ท,วม ร,อุยละ 55 กทมกทม. . อุ,วน ร,อุยละ อุ,วน ร,อุยละ 15.5 15.5 ท,วม ร,อุยละ ท,วม ร,อุยละ 77

รศรศ..พญพญ.. ล!ดดา เหมาะ ล!ดดา เหมาะสวรรณสวรรณ

Childhood obesity: public-health crisis, common sense cureLancet 2002, 360: 473–82

Complications of childhood obesity

Pulmonary involvement in Pulmonary involvement in obesity: overviewobesity: overview

Lung function in obesityLung function in obesity

Asthma and obesityAsthma and obesity

Obstructive sleep apnea and obesityObstructive sleep apnea and obesity

Obesity hypoventilation syndromeObesity hypoventilation syndrome

Postoperative pulmonary Postoperative pulmonary

complications in obese patientscomplications in obese patients

Lung function in obesityLung function in obesity Lung volumeLung volume

FRC, ERV, TLC, VC, TVFRC, ERV, TLC, VC, TV RVRV

Lung mechanics respiratory system compliance work of breathing (WOB)

Flow limitationFlow limitation FEV1FEV1

Others: diffusion capacity (DLco) ventilation-perfusion mismatch O2 consumption and CO2 production

Obesity and asthmaObesity and asthma

Consistent association between obesity and asthma

Temporal association

- Obesity precedes the development of asthma

Dose-response association

- the greater the obesity, the greater the effect on asthma

Obesity and asthma; AJRCC 2006: 174,112-9Obesity and asthma: cause for concern; Curr Opin Pharm 2006,6: 230-6Obesity and asthma, what are the link?; Curr Opin Allergy Clin Immunol 2005,5:185-93

Obesity and Asthma, Am J Respir Crit Care Med 2006 ; 174. 112–119,

ObesityObesity andand asthma :pathophysiologyasthma :pathophysiology

Obesity and Asthma,Am J Respir Crit Care Med2006; 174. 112–119

Obesity and asthma: Obesity and asthma: pathophysiologypathophysiology

Inflammatory factorsInflammatory factors

Obesity and asthma: pathophysiology

Mechanicalfactor

Systemicinflammation

Shared genetic factor

Gender

GERD

Obesity

Prospective studies of obesity and asthma among paediatric patients

ReferenceReference Follow-Follow-upup

(years)(years)

AgeAge

(Year)(Year)SampleSample

sizesizeNo. withNo. with

asthmaasthmaAdjust Adjust forfor

Physical Physical activityactivity

Is increased BMI Is increased BMI associated with associated with asthmaasthma

Chinn & RonaChinn & Rona

G and et al.G and et al.

God et al.God et al.

Castro-Castro-RodriguezRodriguez

et al.et al.

Camago et al.Camago et al.

1212

44

55

44

--

5-65-6

7-187-18

6-146-14

6-116-11

9-149-14

6744 MF6744 MF

3792 MF3792 MF

9828 MF9828 MF

1288 MF1288 MF

16862 16862 MFMF

Approx Approx 285285

288288

805805

--

22122212

NoNo

NoNo

NoNo

NoNo

NoNo

NoNo

Yes (M only)Yes (M only)

Yes (F only)Yes (F only)

Yes (11 years/F Yes (11 years/F only)only)

yesyes

Paediatric asthma and obesity, Paed Resp Rev 2006; 7, 233-8Obesity and asthma; AJRCC 2006: 174,112-9

Studies in children or adolescents•Inconsistent results in the asthma-obesity relation •No convincing evidence for a gender difference

Obesity and asthmaObesity and asthma

Obstructive Sleep Apnea Obstructive Sleep Apnea (OSA) (OSA)and Obesityand Obesity

OSAOSA : : Disorder of breathing during sleep

characterized by prolonged partial upper air

way obstruction / intermittent complete obstr

uction that disrupts normal ventilation durin

g sleep and normal sleep pattern . (ATS. AJRCC.1996

; 153: 866-878)

Prevalence of OSA in obesity 37%- 46%Prevalence of OSA in obesity 37%- 46%

Correlation between degree of obesity and Correlation between degree of obesity and apnea index apnea index

Mallory GB. et al. J Pediatr. 1989:115(6):892-7Mallory GB. et al. J Pediatr. 1989:115(6):892-7Silvestri JM. et al. Ped Pulm. 1993;16(2):124-9Silvestri JM. et al. Ped Pulm. 1993;16(2):124-9Marcus CL. et al. Ped Pul. 1996;21(3):176-83Marcus CL. et al. Ped Pul. 1996;21(3):176-83

OSA:OSA: History * Physical History * Physicalexaminationexamination

Nighttime Nighttime snoring, labored breathing, snoring, labored breathing, paradoxical breathing, paradoxical breathing, restless sleep, apnea restless sleep, apnea, , cyanosiscyanosis, enuresis, enuresis

DaytimeDaytime adenotonsillar hypertrophy, adenotonsillar hypertrophy, mouth breathing mouth breathing nasal obstruction nasal obstruction adenoid facies adenoid facies systemic hypertention systemic hypertention prominent 2nd heart sound prominent 2nd heart sound

Polysomnography(PSG)

OSA and obesity :pathophysiologyOSA and obesity :pathophysiology

OBESITY

UA caliber ↓

UA compliance ↑

UA collapsibility ↑ OSAS

Pharyngeal fat ↑

Abdominal andchest wall fat ↑

Lung volumes ↓

Obesity and weight loss in obstructive sleep apnea: a critical review.Sleep 1996;19:104-115

OSA and OSA and obesity :pathophysiologyobesity :pathophysiology

Increased pharyngeal fatIncreased pharyngeal fat

Increased chest wall and abdominal Increased chest wall and abdominal

fatfat

Tonsil or adenoid enlargementTonsil or adenoid enlargement

Shared genetic factors between OSA Shared genetic factors between OSA

and obesityand obesity• Respiratory complications of obesity. Int J Clin Pract 2004;58:573-80.• Obesity and obstructive sleep apnea in children. Paediatr Respir Rev 2006;7:247-59.• Obstructive sleep apnea, morbid obesity, and adenotonsillar surgery: a review of the literature. Int J Pediatr Otorhinolaryngol 2005;69:1475-82.

OSA and obesityOSA and obesity : : TreatmentTreatment Weight reductionWeight reduction

CPAP or BIPAP CPAP or BIPAP

Adenoidectomy and/or tonsillectomyAdenoidectomy and/or tonsillectomy

Postoperative care in ICUPostoperative care in ICU

RDI ≥ 40

RDI < 40 accompanied by desaturation nadir

< 80%

Presence of cardiac sequelae from OSAObstructive sleep apnea, morbid obesity, and adenotonsillar surgery. Int J Pediatr Otorhinolaryngol. 2005 Nov;69(11):1475-82

Obesity Hypoventilation Obesity Hypoventilation SyndromeSyndrome

DefinitionDefinition: Obesity and awake : Obesity and awake

arterial hypercapnia (PaCOarterial hypercapnia (PaCO2 2 >45 >45

mmHg) in the absence of other mmHg) in the absence of other

known causes of hypoventilationknown causes of hypoventilation

PrevalencePrevalence: 1-3% of obese children: 1-3% of obese children

Risk factorRisk factor: morbid obesity: morbid obesity

Obesity Hypoventilation Obesity Hypoventilation SyndromeSyndrome

Sleep-related Sleep-related breathing disorderbreathing disorder

Hypersomnolence, Hypersomnolence, fatiguefatigue

Morning headacheMorning headache Hypoventilation:Hypoventilation:

PaCO2>45 mmHgPaCO2>45 mmHg PolycythemiaPolycythemia Cor pulmonale Cor pulmonale

ObesityObesity

IncreasedWork of BreathingIncreased

Ventilatory Drive

Leptin Insensitivity ?

Normal Ventilation,Eucapnia

Normal or DiminishedVentilatory Drive

Hypoventilation,Hypercapnia

Obstructive Sleep Apnea Severe SteepHypoxemia

Severe SteepFragmentationMaintain

Normal VentilationHypoventilation

Hypercapnia

ImpairedRespiratory SystemMechanics

Eucapnia

The obesity hypoventilation syndrome. Am J Med 2005;118: 948

Obesity Hypoventilation Obesity Hypoventilation Syndrome:Syndrome:treatmenttreatment

Weight reductionWeight reduction

CPAP or BIPAP CPAP or BIPAP

Adenoidectomy and/or tonsillectomyAdenoidectomy and/or tonsillectomy

Reversibility of hypercapnia to Reversibility of hypercapnia to

normalnormal

Obesity and obstructive sleep apnea in children. Paed resp rev. 2006; 7: 247

Postoperative pulmonary Postoperative pulmonary complications in obese patientscomplications in obese patients Atelectasis: Atelectasis: obesity, anesthesiaobesity, anesthesia Pulmonary embolismPulmonary embolism

: severe obesity, OHS, decreased mobility: severe obesity, OHS, decreased mobility Respiratory failureRespiratory failure

Postoperative carePostoperative care Closed monitoringClosed monitoring Early mobilizationEarly mobilization Chest physiotherapyChest physiotherapy Semiupright positionSemiupright position

Pulmonary complications of obesity. Am J Med sci 2001;321: 249

Pulmonary involvement in obesityPulmonary involvement in obesity

PFT

Asthma

OSA

OHS

PAEDIATRIC RESPIRATORY REVIEWSPAEDIATRIC RESPIRATORY REVIEWS (2006) 7, 233-238(2006) 7, 233-238Paediatric asthma and obesityPaediatric asthma and obesity

ReferenceReference Subjects Subjects (n) (n)

Controls Controls (n)(n)

Fitness measurement and Fitness measurement and trendtrend

Time Time (weeks)(weeks)

Fitch et al.Fitch et al.7070

Orenstein et al.Orenstein et al.7171

Sevonius et al.Sevonius et al.7272

Graff- Lonevig et Graff- Lonevig et al.al.7373

Chai et alChai et al . . 7474

Vamay et alVamay et al..7575

4646

2323

2525

1111

8080

77

10 H 10 H

1313

2525

99

1010

77

PWAPWA

VO2 & PWCVO2 & PWC

PWAPWA

VO2VO2

FitnessFitness

VO2 and VthVO2 and Vth

2020

1616

12-1612-16

8080

4040

1212

Review of controlled trials on the benefits of exercise conditioning in paediatric in patients with asthma

increased decreased ; unchanged; PWC peak word capacity at a heart rate of 170 beatsiminc,VO2, maximum oxygen consumption Vth, ventilatory threshold; H, healthy.

Comorbidities Related to Overweight Comorbidities Related to Overweight in Youthin Youth

MetabolicMetabolicType 2 DMType 2 DM

Metabolic syndromeMetabolic syndrome

OrthopedicOrthopedicSlipped capital femoral epiphysisSlipped capital femoral epiphysis

Blount’s diseaseBlount’s disease

CardiovascularCardiovascularDyslipidemiaDyslipidemia

HypertensionHypertension

Left ventricular hypertrophyLeft ventricular hypertrophy

AtherosclerosisAtherosclerosis

PsychologicalPsychologicalDepressionDepressionPoor quality of lifePoor quality of life

NeurologicalNeurologicalPseudotumor cerebriPseudotumor cerebri

HepaticHepaticNonalcoholic fatty liver diseaseNonalcoholic fatty liver diseaseNonalcoholic steatohepatitisNonalcoholic steatohepatitis

PulmonaryPulmonaryObstructive sleep apneaObstructive sleep apneaAsthmaAsthmaCentral hypoventilation syndromeCentral hypoventilation syndrome

RenalRenalProteinuriaProteinuria

AA Tidal breathingTidal breathing

Large cyclic strains on ASMLarge cyclic strains on ASM

ASM cells compliantASM cells compliant

ObesityObesityBB FRCFRC

PeribronchiPeribronchial pressureal pressure

Tidal Tidal BreathingBreathing

Small cyclic strains on ASMSmall cyclic strains on ASM

ASM cells stiff

ASM cells long, airway caliber ASM cells long, airway caliber largelarge

ASM cells short, airway caliber narrowing

asthma

OSAOSA The increased prevalence and severity of childhood obesity has The increased prevalence and severity of childhood obesity has

translated into increases in the prevalence of obesity-associated translated into increases in the prevalence of obesity-associated

morbidities. morbidities.

Among the multiple morbidities associated with obesity, OSA Among the multiple morbidities associated with obesity, OSA

andand

OHS should be considered and evaluated.OHS should be considered and evaluated.

The classic presentation of children with OSAS as underweight The classic presentation of children with OSAS as underweight

children with adenotonsillar hypertrophy is now being children with adenotonsillar hypertrophy is now being

substantially replaced by patients being overweight.substantially replaced by patients being overweight.

Obese children are at increased risk for developing sleep-Obese children are at increased risk for developing sleep-

disordered breathing and the severity of OSAS is at least disordered breathing and the severity of OSAS is at least

partially explained by the degree of obesity.partially explained by the degree of obesity.

Obstructive sleep apnea may represent an important contributor Obstructive sleep apnea may represent an important contributor

to the association between obesity and metabolic and to the association between obesity and metabolic and

cardiovascular morbidities, by amplification of inflammatory cardiovascular morbidities, by amplification of inflammatory

cascades.cascades.

Obstructive sleep apnea and Obstructive sleep apnea and obesity:obesity:

pathophysiologypathophysiology

Increased pharyngeal fatIncreased pharyngeal fat

Increased chest wall and abdominal fatIncreased chest wall and abdominal fat

Tonsil or adenoid enlargementTonsil or adenoid enlargement

Leptin resistanceLeptin resistance

Shared genetic factors between OSA Shared genetic factors between OSA

and obesityand obesity• Respiratory complications of obesity. Int J Clin Pract 2004;58:573-80.• Obesity and obstructive sleep apnea in children. Paediatr Respir Rev 2006;7:247-59.• Obstructive sleep apnea, morbid obesity, and adenotonsillar surgery: a review of the literature. Int J Pediatr Otorhinolaryngol 2005;69:1475-82.

Obesity Hypoventilation Obesity Hypoventilation SyndromeSyndrome

Obesity

> Leptin-resistance

Leptin

Leptin-resistance

Apneas (intermitentHypoxemia)

Increases inVisceral fat

OSApredisposition

HypercapniaLeptin

Figure 1. In obesity, visceral adiposity is correlatedwith circulating levels of proinflammatory cytokines,and adipose tissue propagates inflammation both locallyand systemically, in part through recruitmentof macrophages via chemokines such as monocytechemoattractant protein-1 (MCP-1) and in part viaelaboration of cytokines and chemokines such as (butnot limited to) leptin, interleukin 6 (IL-6), tumor necrosisfactor (TNF-), transforming growth factor1 (TGF-1), and eotaxin. Although the precise relationshipbetween obesity and asthma remains to bedetermined, modifications of atopy, lung development,Th1–Th2 balance, immune responsiveness, andairway smooth muscle have been hypothesized to bemechanisms by which obesity might increase asthmarisk or modify asthma phenotype. CRP C-reactiveprotein.

Obesity and Asthma, David A. Beuther, Scott T. Weiss, and E. Rand Sutherland

Am J Respir Crit Care Med Vol 174. pp 112–119, 2006

Inflammatory factors