Scientific Letter
Cellular Bronchiolitis: A Late-Onset Non-Infectious Pulmonary Complication After Allogenic Bone Marrow Transplantation
Bronquiolitis celular: una complicación pulmonar no infecciosa de inicio tardío tras un trasplante alogénico de médula ósea
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Is it Different?" 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(B) Chest high resolution computed tomography (HRCT) (lung window) showing interlobular septal thickening along with honeycombing in a basilar and sub-pleural distribution suggestive of UIP pattern. 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However, the incidence of late-onset non-infectious pulmonary complications is 10%–26%, and can be fatal due to progressive respiratory failure.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">1</span></a> We describe a case of cellular bronchiolitis diagnosed 27 years after allogenic BMT.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of a 65-year-old woman, non-smoker, who was diagnosed with acute lymphocytic leukemia at the age of 33 years. After preoperative treatment consisting of busulfan and cyclophosphamide, she received an allogenic BMT from a related donor (her brother), followed by complete remission. At the age of 59 years, she was referred to Aizawa Hospital due to cough and hemoptysis. Thin-section computed tomography (CT) revealed dilated, thick-walled bronchi and tree-in-bud appearance (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). The forced volume capacity (FVC) (%predicted) was 65.3%, and the forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s/FVC was 65.9%. Serologic studies for autoimmune disease (rheumatoid factor, anti-nuclear antibody, SS-A/Ro antibody, and SS-B/La antibody) were all negative. A sputum culture detected <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>, but no species of mycobacteria. She was treated with 200<span class="elsevierStyleHsp" style=""></span>mg clarithromycin once daily, 10<span class="elsevierStyleHsp" style=""></span>mg montelukast once daily, and one puff of 50<span class="elsevierStyleHsp" style=""></span>μg salmeterol twice daily. Her symptoms of cough and hemoptysis decreased after 1 month. However, after 8 months, CT images had not improved. To determine the nature of her lung disease, open biopsy of the left segments 8 and 9 using video-associated thoracoscopy was performed.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Pathologic specimens (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C and D) showed thickening of the wall of membranous bronchioles and the formation of lymphoid follicles with germinal centers due to intraepithelial infiltration of lymphocytes without foamy macrophages. In respiratory bronchioles, reduced intraepithelial infiltration of lymphocytes was observed. However, airway epithelial cell layers were maintained. Therefore, the final pathological diagnosis was cellular bronchiolitis. Thereafter, the patient was treated with three puffs of 160<span class="elsevierStyleHsp" style=""></span>μg budesonide/4.5<span class="elsevierStyleHsp" style=""></span>μg formoterol twice daily, 200<span class="elsevierStyleHsp" style=""></span>mg clarithromycin once daily, and 10<span class="elsevierStyleHsp" style=""></span>mg montelukast once daily. When the thin-section CT images were re-examined 4 years later (at the age of 65), slight improvements were seen (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B).</p><p id="par0020" class="elsevierStylePara elsevierViewall">We reported the case of a patient with cellular bronchiolitis, a late-onset non-infectious pulmonary complications diagnosed 27 years after allogenic BMT. In late-onset non-infectious pulmonary complications, bronchiolitis obliterans (BO) occurs in up to 10% of patients undergoing allogenic BMT.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">1</span></a> The clinical features of BO include progressive airflow limitation, and histological findings are epithelial cell necrosis with denudation of mucosa.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">2</span></a> In this case, an obstructive ventilatory defect was detected; however, in pathologic specimens, airway epithelial cell layers were maintained, which is not the typical pathologic findings of BO.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The median development time for late-onset non-infectious pulmonary complications is about 8–12 months after allogenic BMT, although some cases may be diagnosed after 2–3 years.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">1</span></a> This case was diagnosed 27 years after allogenic BMT. This long interval from allogenic BMT raises the possibility that this is a case of an independent disease and not late-onset non-infectious pulmonary complications of BMT. Radiological findings resembled diffuse panbronchiolitis and follicular bronchiolitis. Diffuse panbronchiolitis is characterized histologically by the presence of mononuclear cells and foamy macrophages in the respiratory bronchioles,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">3</span></a> which did not match the histologic findings in our patient. Follicular bronchiolitis is characterized histologically by the presence of hyperplastic lymphoid follicles with reactive germinal centers distributed along the bronchioles,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">3</span></a> which closely resembled this case. Follicular bronchiolitis is usually associated with collagen vascular diseases, particularly rheumatoid arthritis and Sjogren's syndrome.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">3</span></a> Although this patient did not have clinical or serological features of collagen vascular diseases, the appearance of other symptoms should be investigated.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Recently, the efficacy of azithromycin, leukotriene receptor antagonists, inhaled corticosteroids, and bronchodilators on BO has been investigated.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">4</span></a> Our patient was treated with clarithromycin, montelukast, and budesonide/formoterol without systemic corticosteroids because she refused oral corticosteroids; her condition did not vary. In the future, careful attention should be paid to the patient's disease profiles, because the efficacy of clarithromycin, montelukast, and budesonide/formoterol in cellular bronchiolitis as a late-onset non-infectious pulmonary complication has yet to be fully determined.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Advances in BMT technology have led to improvements in long-term survival after transplantation and diminished the risk of developing late complications, as occurred in our patient. Therefore, long-term survivors of BMT should be carefully followed up.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0040" class="elsevierStylePara elsevierViewall">All authors have no disclosure and financial support regarding this paper.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of Interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors state that they have no conflict of interests.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "xpalclavsec822029" "titulo" => "Abbreviations" ] 1 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 2 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflicts of Interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "abr" "titulo" => "Abbreviations" "identificador" => "xpalclavsec822029" "palabras" => array:4 [ 0 => "BMT" 1 => "BO" 2 => "CT" 3 => "FVC" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Hamada S, Yoshioka T, Higuchi K. Bronquiolitis celular: una complicación pulmonar no infecciosa de inicio tardío tras un trasplante alogénico de médula ósea. Arch Bronconeumol. 2017;53:220–221.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1105 "Ancho" => 1500 "Tamanyo" => 624224 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Thin-section computed tomography image at the age of 59 (A) and 65 (B) and hematoxylin-eosin-stained microscopic image (40×) (C) and (100×) (D).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:4 [ 0 => array:3 [ "identificador" => "bib0025" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incidence, outcome, and risk factors of late-onset noninfectious pulmonary complications after unrelated donor stem cell transplantation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Patriarca" 1 => "C. Skert" 2 => "A. Sperotto" 3 => "D. Damiani" 4 => "M. Cerno" 5 => "A. Geromin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/sj.bmt.1704426" "Revista" => array:6 [ "tituloSerie" => "Bone Marrow Transplant" "fecha" => "2004" "volumen" => "33" "paginaInicial" => "751" "paginaFinal" => "758" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14755316" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0030" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Estenne" 1 => "J.R. Maurer" 2 => "A. Boehler" 3 => "J.J. Egan" 4 => "A. Frost" 5 => "M. Hertz" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J. Heart Lung Transplant" "fecha" => "2002" "volumen" => "21" "paginaInicial" => "297" "paginaFinal" => "310" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11897517" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0035" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Radiologic and pathologic features of bronchiolitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S.J. Pipavath" 1 => "D.A. Lynch" 2 => "C. Cool" 3 => "K.K. Brown" 4 => "J.D. Newell" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Am J Roentgenol" "fecha" => "2005" "volumen" => "185" "paginaInicial" => "354" "paginaFinal" => "363" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0040" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fluticasone, azithromycin, and montelukast treatment for new-onset bronchiolitis obliterans syndrome after hematopoietic cell transplantation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.M. Williams" 1 => "G.S. Cheng" 2 => "I. Pusic" 3 => "M. Jagasia" 4 => "L. Burns" 5 => "V.T. Ho" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bbmt.2015.10.009" "Revista" => array:6 [ "tituloSerie" => "Biol Blood Marrow Transplant" "fecha" => "2016" "volumen" => "22" "paginaInicial" => "710" "paginaFinal" => "716" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26475726" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:3 [ "titulo" => "Acknowledgements" "texto" => "<p id="par0050" class="elsevierStylePara elsevierViewall">We thank Dr. Masanori Kitaichi for his comments regarding histopathologic findings. We also thank Dr. Kenji Misawa and Dr. Osamu Mishima for performing open biopsy using video-associated thoracoscopy.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/15792129/0000005300000004/v1_201704070039/S1579212916301860/v1_201704070039/en/main.assets" "Apartado" => array:4 [ "identificador" => "49861" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Scientific letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15792129/0000005300000004/v1_201704070039/S1579212916301860/v1_201704070039/en/main.pdf?idApp=UINPBA00003Z&text.app=https://archbronconeumol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212916301860?idApp=UINPBA00003Z" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 3 | 11 |
| 2024 October | 85 | 30 | 115 |
| 2024 September | 86 | 24 | 110 |
| 2024 August | 119 | 45 | 164 |
| 2024 July | 92 | 22 | 114 |
| 2024 June | 76 | 28 | 104 |
| 2024 May | 74 | 29 | 103 |
| 2024 April | 58 | 37 | 95 |
| 2024 March | 72 | 24 | 96 |
| 2024 February | 42 | 34 | 76 |
| 2023 March | 17 | 3 | 20 |
| 2023 February | 83 | 19 | 102 |
| 2023 January | 65 | 35 | 100 |
| 2022 December | 97 | 28 | 125 |
| 2022 November | 79 | 26 | 105 |
| 2022 October | 98 | 40 | 138 |
| 2022 September | 113 | 33 | 146 |
| 2022 August | 68 | 45 | 113 |
| 2022 July | 85 | 50 | 135 |
| 2022 June | 103 | 36 | 139 |
| 2022 May | 99 | 42 | 141 |
| 2022 April | 85 | 34 | 119 |
| 2022 March | 97 | 32 | 129 |
| 2022 February | 94 | 36 | 130 |
| 2022 January | 84 | 58 | 142 |
| 2021 December | 79 | 46 | 125 |
| 2021 November | 45 | 45 | 90 |
| 2021 October | 46 | 47 | 93 |
| 2021 September | 40 | 48 | 88 |
| 2021 August | 75 | 47 | 122 |
| 2021 July | 58 | 23 | 81 |
| 2021 June | 87 | 37 | 124 |
| 2021 May | 78 | 39 | 117 |
| 2021 April | 169 | 114 | 283 |
| 2021 March | 107 | 30 | 137 |
| 2021 February | 64 | 17 | 81 |
| 2021 January | 40 | 13 | 53 |
| 2020 December | 58 | 20 | 78 |
| 2020 November | 29 | 22 | 51 |
| 2020 October | 46 | 15 | 61 |
| 2020 September | 46 | 11 | 57 |
| 2020 August | 57 | 22 | 79 |
| 2020 July | 42 | 22 | 64 |
| 2020 June | 39 | 16 | 55 |
| 2020 May | 48 | 13 | 61 |
| 2020 April | 35 | 26 | 61 |
| 2020 March | 29 | 14 | 43 |
| 2020 February | 47 | 19 | 66 |
| 2020 January | 39 | 19 | 58 |
| 2019 December | 47 | 12 | 59 |
| 2019 November | 43 | 25 | 68 |
| 2019 October | 15 | 8 | 23 |
| 2019 September | 31 | 14 | 45 |
| 2019 August | 47 | 23 | 70 |
| 2019 July | 30 | 17 | 47 |
| 2019 June | 22 | 15 | 37 |
| 2019 May | 43 | 11 | 54 |
| 2019 April | 26 | 28 | 54 |
| 2019 March | 42 | 22 | 64 |
| 2019 February | 38 | 20 | 58 |
| 2019 January | 39 | 24 | 63 |
| 2018 December | 37 | 17 | 54 |
| 2018 November | 47 | 22 | 69 |
| 2018 October | 63 | 18 | 81 |
| 2018 September | 29 | 13 | 42 |
| 2018 May | 19 | 1 | 20 |
| 2018 April | 34 | 10 | 44 |
| 2018 March | 30 | 9 | 39 |
| 2018 February | 67 | 12 | 79 |
| 2018 January | 101 | 6 | 107 |
| 2017 December | 103 | 8 | 111 |
| 2017 November | 33 | 7 | 40 |
| 2017 October | 32 | 14 | 46 |
| 2017 September | 30 | 14 | 44 |
| 2017 August | 19 | 22 | 41 |
| 2017 July | 24 | 11 | 35 |
| 2017 April | 1 | 0 | 1 |
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