La BPCO:una malattia pediatrica ?

Domenico MinasiUOC Pediatria

ASP di Reggio Calb ria

Global Strategy for Diagnosis, Management and Prevention of COPD

Burden of COPDGlobal Strategy for Diagnosis, Management and Prevention of COPD

Burden of COPD

COPD is a leading cause of morbidity and mortality worldwide.

The burden of COPD is projected to increase in coming decades due to continued exposure to COPD risk factors and the aging of the world’s population.

COPD is associated with significant economic burden.

COPD is a leading cause of morbidity and mortality worldwide.

The burden of COPD is projected to increase in coming decades due to continued exposure to COPD risk factors and the aging of the world’s population.

COPD is associated with significant economic burden.

© 2015 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD

Mechanisms Underlying Airflow Limitation in COPD

Small Airways Disease• Airway inflammation• Airway fibrosis, luminal plugs• Increased airway resistance

Parenchymal Destruction• Loss of alveolar attachments• Decrease of elastic recoil

AIRFLOW LIMITATION© 2015 Global Initiative for Chronic Obstructive Lung Disease

Until recently, cigarette smoking was considered the main causal factor for developing COPD.

However, evidence from population-based studies now suggests that both indoor and outdoor pollutionand gene–environment interactions make a greater contribution to the burden of COPD than previously

Until recently, cigarette smoking was considered the main causal factor for developing COPD.

However, evidence from population-based studies now suggests that both indoor and outdoor pollutionand gene–environment interactions make a greater contribution to the burden of COPD than previously

Gene-environmentinteractions

Indoor pollution

Outdoor pollution

Cigarette smoking

Until recently, cigarette smoking was considered the main causal factor for developing COPD.

However, evidence from population-based studies now suggests that both indoor and outdoor pollutionand gene–environment interactions make a greater contribution to the burden of COPD than previously

Until recently, cigarette smoking was considered the main causal factor for developing COPD.

However, evidence from population-based studies now suggests that both indoor and outdoor pollutionand gene–environment interactions make a greater contribution to the burden of COPD than previously

Gene-environmentinteractions

Indoor pollution

Outdoor pollution

Cigarette smoking

In addition, there has been growing awareness that the origins of many chronic adult lung diseases such as COPD may arise very

early in life, that is, the ‘foetal origins hypothesis’

Until recently, cigarette smoking was considered the main causal factor for developing COPD.

However, evidence from population-based studies now suggests that both indoor and outdoor pollutionand gene–environment interactions make a greater contribution to the burden of COPD than previously

Until recently, cigarette smoking was considered the main causal factor for developing COPD.

However, evidence from population-based studies now suggests that both indoor and outdoor pollutionand gene–environment interactions make a greater contribution to the burden of COPD than previously

Gene-environmentinteractions

Indoor pollution

Outdoor pollution

Cigarette smoking

The concept that chronic respiratory disease in adulthood is not simply due to an accelerated decline in lung function with ageing, but failure to achieve

optimal peak function by early adulthood due to prior adverse exposures, was first proposed several decades ago

Thorax     January 2010 Vol 65  

Journal of Chronic Obstructive Pulmonary Disease,2008 5:53–67

Developmental adaptations in fetal life and infancy due to early life adverse exposures might result in impaired lung growth with smaller airways, decreased lung volume, and subsequently to an increased risk of  BPD , asthma or COPD. 

Reduced diameter of central and small airways might contribute to the development of chronic obstructive lung diseases

Eur J Epidemiol (2014) 29:871–885

Lancet. 2007 September 1; 370(9589): 758–764

Spirometry was performed at ages 11, 16, and 22 years in 123 unselected subjects whose maximal expiratory flows at function residual capacity (VmaxFRC) had been assessed at a mean age of 2 months by use of the chest compression technique

The results showed that infants in the lowest quartile for VmaxFRC had the lowest mean FEV1/FVC ratios at all ages

Diminished airway function present shortly after birth is a risk factor for airflow obstruction in early adult life

Lancet. 2007 September 1; 370(9589): 758–764

Spirometry was performed at ages 11, 16, and 22 years in 123 unselected subjects whose maximal expiratory flows at function residual capacity (VmaxFRC) had been assessed at a mean age of 2 months by use of the chest compression technique

The results showed that infants in the lowest quartile for VmaxFRC had the lowest mean FEV1/FVC ratios at all ages

COPD is defined as an FEV1/FVC ratio of less 70%

thus subjects who start adult life with lower ratios will attain this theresholdearlier during normal lung aging than

those who start at higher levels

Ther Adv Respir Dis (2013) 7(3) 161–173

Normal lungdevelopment

Prenatal Riskfactors to COPD

Maternal smoking during pregnancy

Maternal obesity pre-pregnancy

Low Birth Weight (LBW)Pre-term birth

Postnatal Riskfactors to COPD

BDPincreased infant

weight gain,Postnatal exposure to environmental tobacco

smokeEnvironmental pollutionChildhood respiratory

illnesses

Early life influences that may predispose to COPD

Ther Adv Respir Dis (2013) 7(3) 161–173

Normal lungdevelopment

Prenatal Riskfactors to COPD

Maternal smoking during pregnancy

Maternal obesity pre-pregnancy

Low Birth Weight (LBW)Pre-term birth

Postnatal Riskfactors to COPD

BDPincreased infant

weight gain,Postnatal exposure to environmental tobacco

smokeEnvironmental pollutionChildhood respiratory

illnesses

Early life influences that may predispose to COPD

Maternal smoking during pregnancy

EFFETTI DEL FUMO IN GRAVIDANZARischio aumentato di aborto e mortalità perinataleBasso peso alla nascita

effetto nel 2° e 3° trimestre solo 1/4 smette in gravidanza e di queste 2/3 ricomincia dopo il parto

Aumentato rischio di SIDS Cancro in età pediatrica ??Peso e altezza minori a 5 e 7 anni di vitaCirconferenza cranica inferiore

Aumentata incidenza malattie respiratorie (indipendente dal fumo passivo post-natale)

Quando una donna fuma, la quantità di ossigeno che raggiunge il cervello del bambino è diminuita di 1 / 3 

Il fumo produce uno stress ossidativo che causa estese lesioni del DNA che possono interferire con il legame della DNA‐metiltransferasi al DNA con il risultato di una ipometilazione 

l’esposizione al fumo durante la vita intrauterina produce importanti e duraturi effetti sulla metilazione del DNA e influisce sull’espressione genica e quindi sui fenotipi di malattia durante il corso della vita.

“…  gli effetti polmonari dell'esposizione alla nicotina durante la gravidanza non sono limitati solo alla prole della gravidanza esposta, ma vengono anche trasmessi ad una successiva generazione attraverso alterazioni epigenetiche della linea germinale “. 

BMC Medicine 2012,10:129

Methods: A pooled analysis was performed based on individual participant data from eight European birth cohorts.

Cohort-specific effects of maternal smoking during pregnancy, but not during the first year, on wheeze and asthma at 4 to 6 years of age were estimated

Am J Respir Crit Care Med   2012

Hannah Burke,  Jo Leonardi

RESULTS:. Exposure to pre‐ or postnatal passive smoke exposure was associated with a 30% to 70% increased risk of incident wheezing and a 21% to 85% increase in incident asthma Exposure to passive smoking increases the incidence of wheeze and asthma in children and young people by at least 20%. 

PEDIATRICS Volume 129, Number 4, April 2012

Eur J Epidemiol (2014) 29:871–885

Eur J Epidemiol (2014) 29:871–885

embryonic and may be the preconception period might be vulnerable periods for adaptations of the lungs and immune system and subsequently development of chronic obstructive lung disease in later life.

Ther Adv Respir Dis (2013) 7(3) 161–173

Normal lungdevelopment

Prenatal Riskfactors to COPD

Maternal smoking during pregnancy

Maternal obesity pre-pregnancy

Low Birth Weight (LBW)Pre-term birth

Postnatal Riskfactors to COPD

BDPincreased infant

weight gain,Postnatal exposure to environmental tobacco

smokeEnvironmental pollutionChildhood respiratory

illnesses

Early life influences that may predispose to COPD

Maternal obesitypre-pregnancy

Erick Forno, MD Omar M. Young, MD, PEDIATRICS Volume 134, Number 2, August 2014  

J Allergy Clin Immunol 2013;131:1033‐40.Maternal obesity during pregnancy was associated with increased risk of asthma and wheezing in offspring but not  with AE and hay fever, suggesting that pathways may be non allergic. 

MOP and high GWG are associated with an elevated risk of childhood asthma; this finding may be particularly significant for mothers without asthma history

Elisabeth T.M. Leermakers Agnes M.M. Sonnenschein‐van der Voort Eur Respir J 2013; 42: 1234–1243

Mothers with pre‐pregnancy obesity and a history of asthma or atopy, and mothers with higher gestational weight gain showed  higher risks of wheezing in their offspring. 

Ther Adv Respir Dis (2013) 7(3) 161–173

Normal lungdevelopment

Prenatal Riskfactors to COPD

Maternal smoking during pregnancy

Maternal obesity pre-pregnancy

Low Birth Weight (LBW)Pre-term birth

Postnatal Riskfactors to COPD

BDPincreased infant

weight gain,Postnatal exposure to environmental tobacco

smokeEnvironmental pollutionChildhood respiratory

illnesses

Early life influences that may predispose to COPD

Low Birth Weight(LBW)

Pre-term birth

MethodsBirth weight of all live twins (8280 pairs) born in Denmark between 1994 and 2000 was linked to information on asthma obtained from parent-completed questionnaires at age 3e9 years.Results Subjects with a history of asthma at age 3e9 years weighed on average 122 g (95% CI 85 to 160) less at birth than subjects who had not developed asthma, p<0.001. There was a linear increase in asthma risk with decreasing birth weight, OR (per 100 g) 1.04 (95% CI 1.03 to 1.05), p<0.001

Thorax 2010;65:146e149

Birth characteristicLow birth weigth

Conclusions Low birth weight is a risk factor for asthma independently of gestational age, sex, birth length and Apgar score, but this may be due, in part, to residual non-genetic confounding factors. This finding lends support to the “fetal origins hypothesis” suggesting undisclosed prenatal determinants for the risk of asthma (and chronic adult lung diseases) .

Thorax 2010;65:146e149

Birth characteristicLow birth weigth

PLOS Medicine January 2014 | Volume 11  

30  studies involving 1,543,639 children 

Preterm birth was associated with an increased risk of wheezing disorders

The risk was particularly high among children born very preterm (32 wkgestation)

Conclusions: There is compelling evidence that preterm birth—particularly very preterm birth—increases the risk of asthma (and chronic adult lung diseases)

Birth characteristcsPre‐term birth

Conclusions: There is compelling evidence that preterm birth—particularly very 

preterm birth—increases the risk of asthma (and chronic adult lung 

diseases)