Diagnostic workup of childhood interstitial lung disease

Abstract

Childhood interstitial lung diseases (chILDs) are rare and heterogeneous diseases with significant morbidity and mortality. An accurate and quick aetiological diagnosis may contribute to better management and personalised treatment. On behalf of the European Respiratory Society Clinical Research Collaboration for chILD (ERS CRC chILD-EU), this review summarises the roles of the general paediatrician, paediatric pulmonologists and expert centres in the complex diagnostic workup. Each patient's aetiological chILD diagnosis must be reached without prolonged delays in a stepwise approach from medical history, signs, symptoms, clinical tests and imaging, to advanced genetic analysis and specialised procedures including bronchoalveolar lavage and biopsy, if necessary. Finally, as medical progress is fast, the need to revisit a diagnosis of "undefined chILD" is stressed.

FIGURE 1

Investigations in childhood interstitial lung disease (chILD) diagnostic workup. a) The investigations are performed one after the other to reach a chILD aetiology. The first step is usually done by the general paediatrician (framed in red), and includes family history, clinical evaluation, chest radiography and routine laboratory tests. b) Age at onset is crucial information that helps to consider some aetiologies more than others. c) Bronchoalveolar lavage (BAL) eliminates infectious causes of ILD and provides clues to the most likely diagnoses. d) When thoracic computed tomography (CT) scan, specific blood tests, BAL and genetic analyses could not assess a diagnosis, lung biopsy is the last step of the diagnostic process, allowing to assess the most likely diagnoses in most cases. NEHI: neuroendocrine cell hyperplasia of infancy; PAP: pulmonary alveolar proteinosis; HSP: hypersensitivity pneumonitis; DAH: diffuse alveolar haemorrhage; PAS: Periodic acid–Schiff; AEC2: type 2 alveolar epithelial cells; LIP: lymphoid interstitial pneumonia; NSIP: non-specific interstitial pneumonia; OB: obliterans bronchiolitis.

FIGURE 2

Stepwise approach to childhood interstitial lung disease (chILD) diagnosis. Workup step 1 represents the general paediatrician's role in chILD diagnostic workup. If the chILD suspicion is confirmed, the patient is referred to paediatric pulmonologists in expert centres for workup step 2: chILD confirmation and aetiological assessment. After specific investigations, usually including molecular analyses and/or lung biopsy, a chILD aetiology can be assessed in most cases. Other patients meet the definition of “undefined chILD”. HRCT: high-resolution computed tomography; BAL: bronchoalveolar lavage; PTI: persistent tachypnoea of infancy; DAH: diffuse alveolar haemorrhage; NEHI: neuroendocrine cell hyperplasia of infancy.