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Although birth represents a radical environmental change for the lung, alterations induced by the birth process tend to be more functional than structural in nature, such that lung development transits smoothly from the prenatal to postnatal period.

At birth, although already functional, the lung is structurally still in an immature condition. Alveoli in newborns are fewer in number and less complex in anatomic detail than in adults. This dissimilarity has led some morphologists to call them ‘saccules’ rather than alveoli (Dunnill, 1962). It has been estimated that there are about 150 million alveoli present at birth compared with approximately 300 million in adults (Hislop et al. 1986).

Following delivery at term, the airspaces present are smooth-walled transitory ducts and saccules with primitive type septa that are thick and contain a double capillary network (Burri, 1984). Between the sixth and eighth postnatal week true alveoli develop rapidly (Boyden, 1967). The respiratory bronchioli elongate and alveoli bulge from the areas o f flattened epithelium. Saccules and transitional ducts are converted into alveolar ducts by their lengthening and by deepening o f the primitive alveoli in their walls (Hislop and Reid, 1974). In the human lung, rapid alvéolisation occurs during the last few weeks o f the prenatal period and the first 5 to 6 months of postnatal life. However, a slower phase must be assumed to last up to the age o f 2 years or even older (Thurlbeck, 1982). Morphometric studies reveal that the human lung volume increases about 23 fold between birth and adulthood. During the same period, the alveolar and capillary surface areas expand about 12 fold and the capillary volume 35 fold (Burri, 1999). During the first few years o f life, there is dysanaptic growth as airways and lung parenchyma develop disproportionately in size. This is because the conducting airways are complete in number at birth and

increase only in size, whereas alveoli increase both in size and in number (Mead, 1980a; Sherrill et al. 1989; Sherrill et al. 1990).

During the first 18 months o f life, as new alveoli form and enlarge, the majority o f the new blood vessels develop at the periphery o f the lung. The small pulmonary arteries reach adult wall thickness within the first few days of life while the larger vessels take up to three months. Beyond this period there is an increase in airway lumen diameter, wall thickness and smooth muscle cell diameter as arteries increase in size as lung volume increases (Hislop, 1995).

Although both collagen and elastin are important in airway development and branching, the interstitium o f the lung contains little collagen and elastin during late gestation and at birth. This may contribute to the ease with which pneumothoraces develop in premature lungs.

Elastin is the primary elastic vertebrate protein responsible for passive recoil as the lungs undergo repeated cycles o f expansion and contraction. Together with collagen fibres, it provides a primary force for expiration (Mariani and Pierce, 1999). Elastin, which appears to be closely related to the development o f alveoli and lung collagen, increases during early postnatal life (Wohl, 1998). The pre- and post-natal development of saccules/alveoli by septation is closely related to the elastic tissue network in the lung parenchyma. Each new septum begins as a crest that is demarcated by an elastic fibre (Hislop and Reid, 1974). Hence a lack o f elastin may result in decreased alveolarisation.

2.8.1 Postnatal airway growth and function

At birth, the basic formation o f cartilaginous airways is complete and additional division does not occur. Growth o f each segment o f the conducting airways appears to occur in a symmetric fashion, both in length and in diameter, until growth o f the thorax ceases (Hislop and Reid, 1974). During the first year o f life there is rapid increase in bronchial smooth muscle especially in the bronchioli. It has been suggested that this rapid increase is related to the change to air breathing and that wall structures o f the healthy lung increase with age in proportion to airway

diameter. However, infants bom prematurely or those requiring artificial ventilation following delivery have increased muscle in peripheral airways (Hislop and Haworth, 1989). Recent findings by Elliot and colleagues have also shown that, among infants who succumbed to SIDS, the inner airway wall thickness was greater in the larger airways o f those whose mothers smoked > 20 cigarettes per day when compared to those infants not exposed to maternal smoking (Elliot et al. 1998). The authors suggest that the increased airway wall thickness may contribute to exaggerated airway narrowing which may explain the diminished airway function observed in infants o f smoking mothers. In asthmatics, airway walls are generally thicker than normal due to the increased amounts o f connective tissue and muscle, hence influencing airway calibre (James et al. 1989), which could have a similar effect.

Conducting airways perform many functions in addition to gas conduction e.g. warming, humidification and cleansing o f inhaled air o f potentially harmful dust particles and micro-organisms. In addition, they have secretory functions. They dilate and contract passively in response to influences such as lung inflation and actively in response to a variety o f humoral and chemical stimuli mediated by the epithelium, smooth muscles, glands, nerves and cells (Jeffery, 1995). In humans, four cell types comprise the surface epithelium o f the conducting airways, namely ciliated, goblet, indeterminate and basal cells. In the terminal bronchioles, Clara cells are also found (Jeffery and Hislop, 1995).

Ciliated cells, the dominant cells of the epithelial layer, are present throughout all conducting airways. The co-ordinated, sweeping motion o f the cilia provides the force that impels the superficial layer o f secretions along its journey from peripheral airways into the pharynx and is an important natural defence mechanism for removing inhaled particles deposited within the lung (Murray, 1986b). In disease there may be widespread loss o f cilia, particularly at sites o f airway branching where air-borne pollutants often impact (Jeffery, 1995).

The main function o f the goblet cell is the secretion o f the correct amount o f mucus with the optimal viscoelastic profile, which is important for the maintenance o f mucociliary clearance (Jeffery, 1995). The number o f goblet cells increases with

diseases such as chronic bronchitis or following inhalation o f tobacco smoke. The basal cell is considered to be the major stem cell from which the more superficial mucus-secreting or goblet cells and ciliated cells derive. The function o f the Clara cell is as yet undetermined. However it acts as the principal stem cell o f small airways where basal and mucous cells are normally sparse and both ciliated and mucous cells may develop from the Clara cell subsequent to its division and differentiation (Jeffrey, 1998).