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Task Force on Chronic Interstitial Lung Disease in Immunocompetent Children

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Task Force on Chronic Interstitial Lung Disease in Immunocompetent Children Copyright #ERS Journals Ltd 2004 Eur Respir J 2004; 24: 686–697 European Respiratory Journal DOI: 10.1183/09031936.04.00089803 ISSN 0903-1936 Printed in UK – all rights reserved ERS TASK FORCE Task force on chronic interstitial lung disease in immunocompetent children A. Clement*, and committee members Committee members: J. Allen, B. Corrin, R. Dinwiddie, H. Ducou le Pointe, E. Eber, G. Laurent, R. Marshall, F. Midulla, A.G. Nicholson, P. Pohunek, F. Ratjen, M. Spiteri, J. de Blic. All members of the Task Force contributed equally to the work. Task force on chronic interstitial lung disease in immunocompetent children. Correspondence: A. Clement, Dept de Pneumo- A. Clement, and committee members. #ERS Journals Ltd 2004. logie Pediatrique - INSERM E213, Hopital ABSTRACT: Chronic interstitial lung diseases in children represent a heterogeneous d9enfants Armand Trousseau, 26 Ave du group of disorders of both known and unknown causes that share common histological Dr Arnold Netter, 75571 Paris cedex 12, France. features. Despite many efforts these diseases continue to present clinical management Fax: 33 144736718 dilemmas, principally because of their rare frequency that limits considerably the E-mail: [email protected] possibilities of collecting enough cases for clinical and research studies. Through a Task Force conducted by the European Respiratory Society, which Keywords: Children, infant, interstitial lung comprised respiratory physicians and basic scientists from across Europe, 185 cases of disease, lung fibrosis interstitial lung diseases in immunocompetent children were collected and reviewed. The present report provides important clinically-relevant information on the current Received: August 5 2003 approach to diagnosis and management of chronic interstitial lung diseases in children. Accepted after revision: June 7 2004 In addition, recommendations for the management of paediatric interstitial lung diseases, as well as new insights into interstitial lung diseases pathophysiology during childhood are discussed. Eur Respir J 2004; 24: 686–697. Chronic interstitial lung diseases (ILD) represent a hetero- various paediatric pulmonary departments in European genous group of disorders of both known and unknown countries, and to collect cases of chronic ILD through a causes that share common histological features. To date, these questionnaire established by the group. This cohort is, thus, disorders have been poorly investigated in children; indeed fairly representative of practice across Europe. Data were most of the strategies used by paediatricians for diagnosis and then pooled and discussed through a series of meetings. treatment are derived from information provided by studies in Chronic ILD in immunocompetent children was defined as adult patients [1, 2]. However, there is increasing evidence the presence of respiratory symptoms and/or diffuse infiltrates that expression and outcome of chronic ILD in children on chest radiographs, abnormal pulmonary function tests differs from adult ILD. The present study was conducted as with evidence of restrictive ventilatory defect and/or impaired part of a European Respiratory Society (ERS) Task Force on gas exchange, and persistence of any of these findings for chronic ILD in immunocompetent children. The objectives of w3 months [1–5]. The medical records of children actively the Task Force were: 1) to provide information on the current managed for chronic ILD in European paediatric centres approach to diagnosis and management of chronic ILD in from 1997–2002 were reviewed. The records of 185 patients children; 2) to provide recommendations to clinicians for the with a diagnosis of chronic ILD were identified based on the diagnosis and management of chronic ILD in children; 3) to criteria defined above, and analysed. The exclusion criteria provide an update on the current understanding of the were lung diseases associated with immunodeficiency and/or pathophysiology of the disease(s) and on ongoing research malignancy. All the information regarding patient back- directions; and 4) to develop clinical and scientific collabora- ground including familial history, patient presentation, tions across the paediatric discipline and also with adult diagnostic evaluation, final diagnosis, treatment and outcome researchers to enable progress in the identification of were recorded through the questionnaire. All the results mechanisms underlying disease initiation and progression in were then collected into a database. In order to provide infants and older children. information on chronic ILD in young children, a subgroup of 58 patients aged v2 yrs was individualised. Results are presented as descriptive data and as mean¡SD. Review of the current approach to diagnosis and management of chronic ILD in children Patient presentation and diagnostic evaluation Study population Paediatric ILD occurred more frequently in the younger The Task Force included clinical respiratory physicians patients (fig. 1). A summary of the patients is listed in table 1. involved in paediatric and adult ILD, as well as basic The prevalence for development of chronic ILD was higher in scientists with expertise in cellular and molecular biology, young males than in young females. This is in agreement with and in genetics. Each member was assigned to contact the other reports [2, 6]. Medical record review of the family members indicated that nearly 10% of case siblings were For editorial comments see page 521. affected by similar diseases. CHRONIC INTERSTITIAL LUNG DISEASE IN CHILDREN 687 25 Table 2. – Diagnostic evaluation of the patients with interstitial lung disease 20 All patients Patients aged v2 yrs Patients n 185 58 15 Chest imaging Infiltrates 128 36 Ground glass pattern 34 11 Cases n 10 Honeycomb pattern 4 1 Pulmonary function tests Sa,O2 122 5 Sa,O2 v95% 73 36 Pa,O2 112 Hypoxaemia 67 26 0 Lung volume 108 <0.5>0.51 2 3 4 5 6 7 8 9 1011121314151617 Restriction 78 ND Age yrs Dco 75 Reduction 43 ND Fig. 1. – Age distribution (in yrs) of the patients with interstitial lung BAL diseases included in the European Respiratory Society Task Force study. Cell population data 98 98 Macrophage % 53.8¡20.9 65.2¡17.1 Lymphocyte % 32.2¡22.6 13.8¡11.6 Table 1. – Clinical presentation of the patients with interstitial Neutrophil % 11.3¡16.5 19.8¡20.5 lung disease Eosinophil % 1.2¡1.6 1.3¡1.6 ¡ All patients Patients aged v2 yrs Data are presented as n or mean SD. Sa,O2: arterial oxygen saturation; Pa,O2: arterial oxygen tension; Dco: diffusion capacity for carbon n% n % monoxide; BAL: Bronchoalveolar lavage; ND: not determined. Patients n 185 58 and neutrophilia; however, in the younger aged children BAL Sex male/female 108/77 58/42 35/23 60/40 cell populations were predominantly neutrophils. Ethnic origin The main laboratory tests performed were microbiology Caucasian 162 87.6 52 89.7 tests, with data available in 111 cases. Positive results were Black 18 9.7 4 6.9 found in 10 samples, with the detection of adenovirus (one Other 5 2.7 2 3.4 case), Epstein Barr virus (EBV; four cases), Influenza virus Parental consanguinity 13 7 5 9 (one case), parvovirus (one case), cytomegalovirus (two cases) Affected siblings 18 10 8 7 and Mycoplasma pneumoniae (one case). The other laboratory Symptoms tests were performed according to the patient history and Cough 145 78 42 73 clinical presentation. Search for circulating auto-antibodies Tachypnoea/dyspnoea 140 76 49 84 was done in 99 samples with positive results in 12 cases. Failure to thrive 68 37 36 62 Elevated levels of angiotensin converting enzyme (ACE) were Fever 37 20 17 29 performed in 10 cases, and screening tests for hypersensitivity Physical findings pneumonitis were considered positive for 20 children. Cyanosis 51 28 31 54 Lung biopsy data were available in 107 cases. Analysis of Clubbing 24 13 5 9 Crackles 81 44 33 57 the diagnostic procedures performed indicated that open lung biopsies were predominantly performed (62%), followed by transbronchial biopsies (26%), video assisted thoracoscopy The majority of patients had symptoms for v1 yr at the biopsies (VATB) (7%), and transthoracic percutaneous time of initial evaluation. The mean duration of symptoms biopsies (5%). before diagnosis was 6.6¡0.5 months. Most children pre- sented with cough and tachypnoea (table 1). Failure to thrive was documented in almost two thirds of the patients Diagnosis diagnosed before aged 2 yrs. Chest radiographs were performed in all patients, but high- A diagnosis was made in 177 of 185 patients, and in 56 of resolution computed tomography (HRCT) scanning data 58 cases in the subgroup of children aged v2 yrs. The list is were available in only 131 of 185 cases (and in 37 of 58 given in table 3, including the number of lung biopsies patients aged v2 yrs). Abnormalities at the time of initial performed. Some can be considered as specific diagnoses, in evaluation were predominantly interstitial infiltrates (table 2). accordance with the standard classification of chronic ILD Analysis of the pulmonary function data showed large [6, 7]. They include pulmonary haemosiderosis, pulmonary variations in the methods used by the various paediatric alveolar proteinosis, hypersensitivity pneumonitis, Langerhans centres. The results summary of gas exchange analysis, lung cell histiocytosis, sarcoidosis, pulmonary lymphangioleiomyo- volumes, and diffusion capacity for carbon monoxide (Dco) matosis, lymphocyte infiltrative disorders, and auto-immune tests that could be included in the present review are related
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