Diagnostic Evaluation and Clinical Findings in Children With Persistent Tachypnea of Infancy and Neuroendocrine Cell Hyperplasia of Infancy: A European Multicenter Retrospective Study.

Abstract

Background: Persistent tachypnea of infancy (PTI) or neuroendocrine cell hyperplasia of infancy (NEHI) is a form of childhood interstitial lung disease (chILD) that predominantly affects young children. Although it is one of the most common chILDs, no unified diagnostic approach specific to this condition exists.

Research question: Are the clinical presentation and the diagnostic approach different in patients with PTI or NEHI among the European countries?

Study design and methods: This was a European multicenter, retrospective, observational study. Data on clinical characteristics and diagnostic strategies in patients with PTI or NEHI were analyzed and compared across participating countries.

Results: The study included 378 children with PTI or NEHI from 17 countries (63.5% male, 97.4% White) who received a diagnosis at a median age of 9 months (interquartile range, 6-13 months). The most common baseline symptoms were tachypnea, chest retractions, crackles on auscultation, hypoxemia, and failure to thrive. High-resolution CT (HRCT) imaging was performed in all patients, with most undergoing chest radiography, echocardiography, and immunology tests. Lung biopsy was carried out in 23.5% of patients, with a decreasing trend over time and variation by country; its use was associated with longer diagnostic delay. Histopathologic examination showed a hyperplasia of pulmonary neuroendocrine cells in 52.8% of patients. Genetic testing was rare, and its application varied significantly among countries. Additional investigations that do not have an established role, such as assessment for gastroesophageal reflux disease and OSA, infant pulmonary function tests, and lung ultrasound, were limited to single countries.

Interpretation: Diagnosis of PTI or NEHI relies on clinical symptoms and HRCT imaging results, with lung biopsies less commonly performed. Differences exist among countries regarding the number and type of investigations. A need exists for guidelines that will uniform the diagnostic approach.