{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T16:08:04Z","timestamp":1770480484184,"version":"3.49.0"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2005,10,21]],"date-time":"2005-10-21T00:00:00Z","timestamp":1129852800000},"content-version":"vor","delay-in-days":3977,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[1994,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The increased survival rate of malignant diseases due to more aggressive treatments contributes to the occurrence of drug\u2010induced pulmonary diseases (DIPD). We reviewed, retrospectively over a 10\u2010year period, 15 children (8 girls) who presented a DIPD. Their mean age was 9 years (range, 1 to 17 years), with an underlying malignant disease in 14 (9 leukemias). Three typical patterns have emerged from this analysis: (1) acute hypersensitivity lung disease caused by methotrexate (in 6 patients) or azathioprine (in 1 patient). This acute syndrome consisted of alveolar\u2010interstitial infiltrate with a hypercellularity on bronchoalveolar lavage (BAL) (mean, 714,286 cells\/mL; range, 180,00\u20142,940,000 cells\/ml) and an increase of lymphocyte counts (mean, 39%; range 1144%) with predominantly CD8\u2010suppressor\/cytotoxic lymphocytes. Inhibition of leukocyte migration or leukocyte aggregation in the presence of low drug concentrations was positive in the 5 cases tested. Lung function tests showed a restrictive pattern and the outcome of DIPD was always favorable. (2) Chronic pneumonitis\/fibrosis was seen in 6 patients who received a variable association of cyclophosphamide (3 patients), bleomycin (2 patients), BCNU (2 patients), and melphalan (1 patient). Symptoms of an alveolar\u2010interstitial pneumonitis developed progressively. BAL showed a moderate increase of total cell numbers (mean, 495,000 cells\/mL; range, 150,000\u2014900,000 cells\/mL). Lung function tests showed a restrictive pattern. Despite corticosteroid treatment in 4 children, one died after bleomycin lung injury and 2 had functional lung impairment. (3) Noncardiogenic pulmonary edema occurred in 2 patients with leukemia treated with recombinant interleukin II. BAL showed hypercellularity and outcome was rapidly favorable. This study reports on the occurrence and severity of DIPD in infants and children. DIPD may be underdiagnosed because of inefficiencies in systematic lung evaluation in children treated with cytotoxic drugs.<jats:bold>Pediatr Pulmonol. 1994;18:347\u2013355.<\/jats:bold> \u00a91994 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ppul.1950180602","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T20:06:12Z","timestamp":1173211572000},"page":"347-355","source":"Crossref","is-referenced-by-count":38,"title":["Cytotoxic drug\u2010induced pulmonary disease in infants and children"],"prefix":"10.1002","volume":"18","author":[{"given":"Brigitte","family":"Fauroux","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arlette","family":"Meyer\u2010Milsztain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliane","family":"Boccon\u2010Gibod","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy","family":"Leverger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annick","family":"Cl\u00e9ment","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Biour","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy","family":"Tournier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,10,21]]},"reference":[{"key":"e_1_2_1_2_2","first-page":"321","article-title":"Drug\u2010induced pulmonary disease. Part I: Cytotoxic drugs","volume":"133","author":"Cooper JAD","year":"1986","journal-title":"Am Rev Resp Dis."},{"key":"e_1_2_1_3_2","volume-title":"Treatment\u2010Induced Respiratory Disorders. Drug Induced Disorders","author":"Akoun G","year":"1989"},{"key":"e_1_2_1_4_2","first-page":"345","article-title":"Drug\u2010induced pulmonary reactions in children, a review","volume":"84","author":"Blaiss MS","year":"1990","journal-title":"Southern Med J."},{"key":"e_1_2_1_5_2","first-page":"34","article-title":"The pulmonary toxicity of antineoplastic agents","volume":"9","author":"Ginsberg SJ","year":"1982","journal-title":"Semin Oncol."},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199008093230604"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198007243030403"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1979.03300070019017"},{"key":"e_1_2_1_9_2","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1001\/jama.1979.03300070029018","article-title":"An algorithm for the operational assessment of adverse drug reactions. II. Demonstration of reproductibility and validity","volume":"242","author":"Hutchinson TA","year":"1979","journal-title":"JAMA"},{"key":"e_1_2_1_10_2","first-page":"332","article-title":"Technique et r\u00e9sultats normaux du lavage broncho\u2010alveolaire chez I'enfant sain","volume":"11","author":"Grimfeld A","year":"1983","journal-title":"Rev Fr Mal Resp."},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.1950050102"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.42.10.759"},{"key":"e_1_2_1_13_2","first-page":"104","article-title":"Resistance pulmonaire totale, compliance pulmonaire dynamique (chez I'enfant de 3 \u00e1 5 ans). Principe, discussion des valeurs normales, int\u00e9\u011bt de la mesure","volume":"50","author":"Gauthier C","year":"1974","journal-title":"Sem Hop Pans"},{"key":"e_1_2_1_14_2","first-page":"411","article-title":"Lung transfer factor for CO at rest in normal children by a steady\u2010state method","volume":"18","author":"Chaussain M","year":"1982","journal-title":"Bull Eur Physiopathol Respir."},{"key":"e_1_2_1_15_2","first-page":"289","article-title":"Determination of capillary oxygen tension in infants and children. Assessment of methodology and normal values during growth","volume":"14","author":"Gaultier C","year":"1978","journal-title":"Bull Eur Physiopathol Respir."},{"key":"e_1_2_1_16_2","first-page":"431","article-title":"Exploration fonctionnelle respiratoire de I'enfant","volume":"3","author":"Gaultier C","year":"1986","journal-title":"Rev Mal Resp."},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1136\/adc.65.5.548"},{"key":"e_1_2_1_18_2","first-page":"57","article-title":"Lung function in interstitial diseases in children","volume":"16","author":"Gaultier C","year":"1980","journal-title":"Bull Eur Physio pathol Respir."},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(82)90242-3"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.91.1.96"},{"key":"e_1_2_1_21_2","first-page":"843","article-title":"Le test d'aggregation leucocytaire dans l'\u00e9valuation de I'immunit\u00e9 B m\u00e9diation cellulaire. Adaptation B l'allergie m\u00e9dicamenteuse","volume":"11","author":"Rouveix B","year":"1982","journal-title":"Nouv Presse Med."},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.1983.tb02562.x"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197605)37:5<2414::AID-CNCR2820370533>3.0.CO;2-J"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.128.1.15"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19800115)45:2<236::AID-CNCR2820450207>3.0.CO;2-0"},{"key":"e_1_2_1_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19910815)68:4<699::AID-CNCR2820680406>3.0.CO;2-5"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.85.4.514"},{"key":"e_1_2_1_28_2","first-page":"232","article-title":"Comparative study of T\u2010cell subsets in BAL fluid in patients with hypersensitivity pneumonitis and sarcoidosis","volume":"82","author":"Hirata T","year":"1982","journal-title":"Chest"},{"key":"e_1_2_1_29_2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.42.9.652"},{"key":"e_1_2_1_30_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-197609000-00002"},{"key":"e_1_2_1_31_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.6109.330"},{"key":"e_1_2_1_32_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.91.1.96"},{"key":"e_1_2_1_33_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.94.5.1050"},{"key":"e_1_2_1_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)93367-I"},{"key":"e_1_2_1_35_2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.38.12.951"},{"key":"e_1_2_1_36_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.83.4.696"},{"key":"e_1_2_1_37_2","first-page":"73","article-title":"La pneumopathie d'hypersensibilit\u00e9 \u00e0 I'azathioprine. Donn\u00e9es en faveur d'un m\u00e9canisme immunologique","volume":"41","author":"Akoun G","year":"1986","journal-title":"Th\u00e9rapie"},{"key":"e_1_2_1_38_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.77.6.805"},{"key":"e_1_2_1_39_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.235.12.1253"},{"key":"e_1_2_1_40_2","first-page":"1267","article-title":"Ultrastructural study of pulmonary bleomycin toxicity","volume":"35","author":"Daskal Y","year":"1976","journal-title":"Cancer Res."},{"key":"e_1_2_1_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-5231(21)00668-7"},{"key":"e_1_2_1_42_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.6128.1664"},{"key":"e_1_2_1_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(83)91009-4"},{"key":"e_1_2_1_44_2","first-page":"592","article-title":"Enhanced bleomycin toxicity during acute renal failure","volume":"66","author":"Perry DJ","year":"1982","journal-title":"Cancer Treat Rep."},{"key":"e_1_2_1_45_2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.48.1.92"},{"key":"e_1_2_1_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/0090-8258(89)90629-X"},{"key":"e_1_2_1_47_2","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.152.4.749"},{"key":"e_1_2_1_48_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.176.1.2353090"},{"key":"e_1_2_1_49_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.94.4.750"}],"container-title":["Pediatric Pulmonology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fppul.1950180602","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ppul.1950180602","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T09:13:27Z","timestamp":1698225207000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ppul.1950180602"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,12]]},"references-count":48,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1994,12]]}},"alternative-id":["10.1002\/ppul.1950180602"],"URL":"https:\/\/doi.org\/10.1002\/ppul.1950180602","archive":["Portico"],"relation":{},"ISSN":["8755-6863","1099-0496"],"issn-type":[{"value":"8755-6863","type":"print"},{"value":"1099-0496","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,12]]}}}