Direct and indirect effects of Growth Hormone Deficiency (GHD) on lung function in children: A mediation analysis

Carla Giordano, Nicola Scichilone, Giuliana Ferrante, Salvatore Fasola, Giovanna Cilluffo, Giancarlo Tancredi, Stefania La Grutta, Giancarlo Tancredi, Giovanni Viegi

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1 Citation (Scopus)


Background: Studies on pulmonary function tests (PFTs) in Growth Hormone Deficiency (GHD) children are lacking. The aims of this study were: (i) to investigate PFTs in GHD pre-pubertal children with respect to Controls, before starting Growth Hormone Therapy (GHT) (T0); (ii) to evaluate changes of PFTs in GHD vs Controls, after 1-year GHT (T1). Forboth aims the mediation analysis (MA) was applied to evaluate the extent to which the relationship between GHD and PFTs could be ascribed to a height-mediated (indirect) or a GH direct effect. Methods: 47 pre-pubertal GHD children (aged 5–14 years) underwent PFTs at T0 and T1. At T0, 47 healthy children matched for age and sex were enrolled as Controls. A MA was performed to assess the relationship between GHD and PFTs and height. Statistical analyses were performed using the statistical software R (https:// A p-value<0.05 was considered significant. Measurements and main results: At T0, PFTs indices were significantly lower in GHD than in Controls. From T0 to T1 a significant improvement was found in PFTs. The percentages of the mediated effect on FVC, FEV1, FEF25–75% and TLC were<50% at T0, suggesting that the direct effect was prevalent. At T1, the percentages of the mediated effect for spirometry indices were ≥50%, indicating that the indirect (height-mediated) effect was the most relevant. Conclusions: The study shows that pre-pubertal children with GHD have an impairment of lung function not exclusively attributable to the indirect (height-mediated) effect, but also to the direct GH action which is mitigated after 1-year of GHT.
Original languageEnglish
Pages (from-to)61-69
Number of pages9
JournalRespiratory Medicine
Publication statusPublished - 2018

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine


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