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Pulmonary function in children with homozygous alpha1-protease inhibitor deficiency
W Wiebicke1, B Niggemann, A Fischer
1University Children's Hospital (KAVH), Berlin, Germany.
Insights
Children with alpha1-protease inhibitor (alpha1-PI) deficiency typically show normal lung function. Regular lung function monitoring can identify children who may benefit from alpha1-PI augmentation therapy.
Area of Science:
- Pulmonology
- Genetics
- Pediatrics
Background:
- Alpha1-protease inhibitor (alpha1-PI) deficiency is a known cause of emphysema in adults.
- The natural history and pulmonary implications of alpha1-PI deficiency in children remain largely uncharacterized.
Purpose of the Study:
- To investigate the pulmonary function and clinical status of children with homozygous alpha1-PI deficiency (PiZZ phenotype).
- To compare lung function parameters between PiZZ children and healthy controls.
Main Methods:
- A cohort of 17 homozygous alpha1-PI deficient children (PiZZ) and 17 age-matched healthy schoolchildren underwent pulmonary function testing (spirometry, plethysmography, diffusing capacity).
- Serum alpha1-PI levels, PI phenotype, and liver function tests were assessed.
- Statistical analysis was performed using the Wilcoxon test.
Main Results:
- PiZZ children had significantly lower serum alpha1-PI levels (16% of control values).
- No significant differences in overall pulmonary function parameters were observed between the PiZZ group and controls.
- Mild expiratory obstructive airway disease and hyperinflation were noted in one symptomatic 18-year-old PiZZ female, unresponsive to bronchodilators.
Conclusions:
- The majority of children with homozygous alpha1-PI deficiency exhibit normal lung function.
- Serial lung function measurements are recommended to identify individuals who may require alpha1-PI augmentation therapy.
Unlabelled:
Alpha1-protease inhibitor (alpha1-PI) deficiency is a well-recognized cause of emphysema in adults; however, the natural history of this disorder in children is unclear. Because of the paucity of data in the paediatric age group, we performed whole body plethysmography, spirometry, and diffusing capacity, in a cohort of 17 homozygous (PiZZ phenotype) children (9 females, 8 males; mean age +/- SEM 13.4 +/- 0.9, range 7-18 years) and in 17 normal schoolchildren (13.5 +/- 0.9, 7-18 years), using a matched-pair design. Blood was drawn for determination of serum alpha1-PI levels, PI phenotype, and standard biochemical tests of liver function. Among the PiZZ subjects, 12 were detected during diagnostic workup of prolonged neonatal icterus, and 5 by routine testing in paediatric patients. None had chronic respiratory symptoms except for an 18-year-old PiZZ girl with a history of recent onset of exertional dyspnoea. All were non-smokers. The Wilcoxon test was used for statistical analysis. As expected, serum alpha1-PI levels were lower in the PiZZ group (16% of the control value). A few patients had slight elevations of their liver enzymes. As for the pulmonary function parameters, differences between groups were not significant. Individual data showed no consistent abnormality in lung function except for signs of mild expiratory obstructive airway disease with hyperinflation (elevated TGV/TLC ratio) in the only symptomatic 18-year-old subject (0.63, control subject 0.49). This was unresponsive to bronchodilators. For her, augmentation therapy with intravenous infusion of alpha1-PI may be considered.
Conclusion:
Our study confirms the absence of pulmonary function abnormalities in the vast majority of children with homozygous alpha1-PI deficiency. Serial measurements of lung function may help to distinguish those individuals who require treatment with alpha1-PI from those who do not.