“The womb may be more important than the home”.
D J P Barker; BMJ Volume 301 17 November 1990

Acknowledgment that there are early factors that determine and influence the emergence of diseases late in life has been demonstrated in the relation between weight at birth and cardiovascular disease, which is known as the Barker hypothesis.

Studies undertaken in Norway, Finland, the United Kingdom, and the USA reveal mortality rates by cardiovascular disease that are inversely proportional to the height of populations, and geographic differences in cardiovascular mortality related to former differences in infant mortality rates. Records from the previous century enabled establishing a connection between weight at birth, breastfeeding, and cardiovascular disease. These epidemiological findings point to the influence of adverse conditions in life, such as housing and diet, in the rise of the risk of coronary ischemic disease, and suggest the existence of early programming with late influence in several diseases.

This paradigm change, which goes together with the replacement of infectious diseases by degenerative ones, also extends to chronic obstructive pulmonary disease (COPD), whose origins in early paediatric ages result from knowledge of early pulmonary development, from longitudinal studies of sibilant diseases, and the capacity to carry out respiratory functional studies (RFS) at all paediatric ages, which was not possible earlier.

The evident connection between respiratory diseases at paediatric age and chronic pulmonary disease in adults goes back some time. From surveys carried out with a group of 2.626 adults above the age of 20, in Tucson, Arizona, about thirty years ago, Burrows et al. described the relation between respiratory infections at paediatric age and the prevalence of respiratory symptoms and obstructive pulmonary disease at adult age. In one of their studies, they declared there was a connection between respiratory infections at paediatric age and the accelerated decline of the respiratory function with age and cigarette consumption.

In 1986, Barker et al, in the analysis made of death certificates of a large number of individual in a vast geographical area and in distinct communities in England and Wales, correlated mortality by respiratory infections at paediatric age occurred in 1921-5 with mortality by COPD around fifty years later (1968-78).

Burrows’ studies led, in the 1980s, to the largest prospective longitudinal study starting at birth. Tucson’s results have influenced, in the past decades, diagnosis and therapeutic intervention in sibilant respiratory disease in the first years of life, from discrimination presupposes between sibilance phenotypes, with prognosis implications that are not yet completely established.

The most recent epidemiological studies, started in the 1980s, are not yet sufficiently long to define, in absolute terms, functional respiratory evolution, from the neonatal period to old age and death. However, conclusions, albeit incomplete and deduced from superimposition of results, demonstrate the prolonged influence that early alterations of the respiratory function have throughout life.

Naturally, the development of respiratory function determination equipments and methodologies, adapted to the distinct paediatric ages, has played a preponderant role in these conclusions. The standardization of methodologies and recommendations for their use and interpretation enable to even out the results from these studies and obtain extrapolated conclusions from and for distinct populations. Longitudinal studies of the respiratory function have shown that pulmonary and airways growth follows a pre-established route, which the Anglo-Saxon call tracking, according to which individual respiratory function tends to remain in the same relative position (same curve or canal) throughout life (Figure 1). Whereas airways are fully present at the time of birth, only growing in size as individuals grow, alveoli grow in size and number. After the age of 2, parenchymatous growth is mainly due to alveolar growth. Accordingly, it is possible that from that stage, the airways and alveolar spaces show isotropic growth.

Respiratory function studies in premature babies have shown that independently from having been considered healthy (without respiratory complications or requiring minimum ventilator assistance) or from having been considered to have bronchopulmonary (BPD) dysplasia, they both present alterations of the respiratory function.

With regard to the first group, this is probably due to the interruption of normal growth and of pulmonary alveolarisation. In the case of the latter, and besides these factors, this was due to direct aggression provoked by the ventilation system and oxygen free radicals.

BPD provides an extreme but illustrative example that genetic predisposition, environmental factors, and their respective integration in critical periods in life can decisively influence phenotypic expression in the following decades. Evidence suggests that the same applies to asthma and COPD.

The antenatal factors which are more relevant in determining respiratory function reduction and predisposition for respiratory disease at a paediatric age are cigarette consumption during pregnancy, maternal atopy and factors leading to low-weight birth in terms of gestational age, including mother’s hypertension, some medicines and low weight at birth, whereas, in a monotonous way, the post-natal early adverse triggering factors include passive smoking, respiratory infections, and environmental factors related mostly with the quality of the air inside the homes.

Therefore, effective prevention of COPD in adults cannot be limited to quitting smoking habits at adult age, although the prevention of smoking should not be neglected, as it has a potential trigger effect. Equally important are campaigns aiming to prevent smoking habits during paediatric age and pregnancy, improved obstetric conditions, and particular attention to nutrition. Obesity, which will become the next epidemic, will have clear consequences in determining COPD.

Unquestionably, understanding any chronic obstructive pulmonary disease requires knowledge of antenatal pulmonary growth and development, of endogenous and exogenous risk factors and their interactions in windows of susceptibility. Viral infections, which may have effects and stay latent for many years, which is the case of adenovirus, justify studies that define the eventual interaction with genetic susceptibilities, environment and antenatal pulmonary lesion.

Teresa Bandeira
Paediatric Pneumology Unit and Paediatric Centre for Respiratory Function, Sleep and Ventilation Studies.
Paediatric University Clinic.
Child and Family Department. HSM. CHLN
Graduate Pneumology Hospital Assistant. Guest Assistant at FML.
teresa.bandeira@hsm.min-saude.pt

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