ReviewEarly onset children’s interstitial lung diseases: Discrete entities or manifestations of pulmonary dysmaturity?
Section snippets
NEHI: Dysmaturation of the foetal airways?
NEHI is a term which was coined to describe otherwise well infants with any or all of chronic tachypnoea, retractions, crackles and hypoxaemia; in lung biopsies haematoxylin and eosin (H&E) staining was essentially normal, but there was increased staining for the neuropeptide bombesin in the most distal airway cells [16], [17], [18]. If performed, infant pulmonary function tests show evidence of air trapping [18], [19], and airflow obstruction persists into childhood [20]. High resolution CT
Dysmaturation of the foetal mesenchyme (PIG)
PIG was first described [14] in seven infants who presented with tachypnoea, respiratory distress and non-specific pulmonary infiltrates in the first month of life. Light and electron microscopy confirmed the presence of glycogen granules within spindle shaped cells which expanded the interstitium. These cells were vimentin positive but negative for macrophage markers. There was no pathological extrapulmonary glycogen deposition. Six infants survived; the seventh died of the complications of
Dysmaturation of the foetal pulmonary vasculature
The foetal pulmonary vascular resistance (PVR) is high, leading to physiological right to left shunting because the foetal lung has no gas-exchange function. Reflecting this, there is substantially more muscularisation of the distal pulmonary arteries and arterioles than in childhood. Furthermore, the greatly reduced numbers of alveoli in the foetal lung compared to the mature lung contributes to the elevated PVR. At birth, as the lung expands with the first breaths, PVR normally falls and
Conclusions
Just as elsewhere it has been argued that deconstructing the airway is a good way to approach treatment [83], here we advance the hypothesis that growth and maturational disorders should be deconstructed into dysregulated development of alveoli, airway, mesenchyme and pulmonary circulation. This is a controversial hypothesis which requires testing. Perhaps these should be called ‘lung dysmaturation syndromes’ if lung tissue is available, specifying which compartment(s) are affected. As with
Educational aims
The reader will come to:
- 1.
Appreciate the spectrum of interstitial lung diseases presenting early in life related to abnormalities of lung development (NEHI, PIG, alveolar-capillary dysplasia spectrum).
- 2.
Realise that these may not be specific entities, but there are overlap syndromes and associations with extrapulmonary abnormalities.
- 3.
Understand that these histological patterns are the beginning not the end of the diagnostic journey, and should trigger a search for underlying in particular genetic
Directions for future research
- 1.
Determine the spectrum of genes important in antenatal lung development, in which mutations may present as interstitial lung disease.
- 2.
By moving from identification of histological patterns to underlying gene mutations, to move from non-specific or no therapies to specific, targeted molecular treatments for these conditions.
Acknowledgements
AB is an NIHR Senior Investigator. Supported by chILD-EU (FP7, No, 305653) and the European Cooperation in Science and Technology COST A16125.
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