Letter to the Editor
Allergic bronchopulmonary aspergillosis treated successfully with omalizumab
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(A, B) Rapidly progressive ulcer with abundant purulent exudate. (C) Application of the system of negative aspiration (NPWT) on the ulcer bed. (D) Result after 7 days using the NPWT system and immunosuppression, where we can observe the disappearance of the exudate and the emergence of granulation tissue. (E) 6 months after onset we can observe that the lesion is fully healed.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J. Soro-García, E.M. García-Fontán, R. Carrasco-Rodríguez, M. Blanco-Ramos, M.A. Cañizares-Carretero" "autores" => array:5 [ 0 => array:2 [ "nombre" => "J." "apellidos" => "Soro-García" ] 1 => array:2 [ "nombre" => "E.M." "apellidos" => "García-Fontán" ] 2 => array:2 [ "nombre" => "R." "apellidos" => "Carrasco-Rodríguez" ] 3 => array:2 [ "nombre" => "M." "apellidos" => "Blanco-Ramos" ] 4 => array:2 [ "nombre" => "M.A." "apellidos" => "Cañizares-Carretero" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173511517300933?idApp=UINPBA00004E" "url" => "/21735115/0000002300000005/v1_201709150948/S2173511517300933/v1_201709150948/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S217351151730074X" "issn" => "21735115" "doi" => "10.1016/j.rppnen.2017.05.002" "estado" => "S300" "fechaPublicacion" => "2017-09-01" "aid" => "1250" "copyright" => "Sociedade Portuguesa de Pneumologia" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Rev Port Pneumol. 2017;23:303-4" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1719 "formatos" => array:3 [ "EPUB" => 174 "HTML" => 980 "PDF" => 565 ] ] "en" => array:9 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Does omalizumab impair glucose homeostasis in a patient with severe persistent asthma and type 2 diabetes mellitus?" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "303" "paginaFinal" => "304" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "S. Hamada, A. Kuroe, M. Tsukino" "autores" => array:3 [ 0 => array:2 [ "nombre" => "S." "apellidos" => "Hamada" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Kuroe" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Tsukino" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S217351151730074X?idApp=UINPBA00004E" "url" => "/21735115/0000002300000005/v1_201709150948/S217351151730074X/v1_201709150948/en/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Allergic bronchopulmonary aspergillosis treated successfully with omalizumab" "tieneTextoCompleto" => true "saludo" => "Dear Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "304" "paginaFinal" => "306" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "R. Aguiar, N.P. Fernandes, A. Lopes, C. Lopes" "autores" => array:4 [ 0 => array:4 [ "nombre" => "R." "apellidos" => "Aguiar" "email" => array:1 [ 0 => "aguiar2016@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "N.P." "apellidos" => "Fernandes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "A." "apellidos" => "Lopes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "C." "apellidos" => "Lopes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Immunoallergology Department, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Pneumology Department, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Allergic bronchopulmonary aspergillosis (ABPA) is caused by a hypersensitivity response of type 2 T helper (Th2) lymphocytes to antigens, mostly <span class="elsevierStyleItalic">Aspergillus fumigatus</span> (<span class="elsevierStyleItalic">A. fumigatus</span>).<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> This abnormal host response to <span class="elsevierStyleItalic">A. fumigatus</span> in a subset of patients with asthma or cystic fibrosis (CF) is likely due to genetic susceptibility that predisposes patients to the risk of developing ABPA. This is characterised by an increased total IgE and <span class="elsevierStyleItalic">Aspergillus</span>-specific IgE, IgG, and IgA in the serum and bronchoalveolar lavage.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> The International Society for Human and Animal Mycology (ISHAM) and the Rosenberg–Patterson criteria are most often used to diagnose ABPA.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Omalizumab</span> is a humanized monoclonal anti-IgE antibody with licensed indication in severe allergic asthma. There are clinical studies that have also shown benefit in the use of <span class="elsevierStyleItalic">omalizumab</span> in ABPA patients without and with cystic fibrosis.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5,6</span></a> However, the safety and efficacy of <span class="elsevierStyleItalic">omalizumab</span> in ABPA needs further evidence.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The authors described a 45-year-old caucasian man with long standing atopic asthma with frequent exacerbations, and ABPA diagnosed at the age of 42 years. CF was excluded. At the time of ABPA diagnosis, his predicted forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s (FEV1) was 58% and after bronchodilator was 62%. All Rosenberg–Patterson criteria were met, including central bronchiectasis with pulmonary infiltrates in all lobes evidenced in a thoracic CT scan. Peripheral blood eosinophils were 570/mm<span class="elsevierStyleSup">3</span> under systemic steroids, total IgE was 2674<span class="elsevierStyleHsp" style=""></span>IU/mL and AF-specific IgE was 30.50<span class="elsevierStyleHsp" style=""></span>kU/L. No precipitating antibody against AF antigen was found. The patient was treated with prednisolone 40<span class="elsevierStyleHsp" style=""></span>mg/day, inhaled salmeterol/fluticasone propionate combination 50/500<span class="elsevierStyleHsp" style=""></span>mcg twice a day and montelukast 10<span class="elsevierStyleHsp" style=""></span>mg/day. We could not taper the prednisolone dose because of frequent exacerbations.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Oral itraconazole was not administered because the patient was taking atorvastatin (since a previous cerebral stroke), and also because of his history of hepatotoxicity due to azathioprine (which he has been prescribed in the past for his severe dermatitis).</p><p id="par0025" class="elsevierStylePara elsevierViewall">Despite the optimising treatment, frequent exacerbations of his pulmonary disease occurred. So, one year after ABPA diagnosis the patient began treatment with <span class="elsevierStyleItalic">omalizumab</span> 600<span class="elsevierStyleHsp" style=""></span>mg subcutaneously every 2 weeks (the maximum recommended dosage; dose and dose frequency were based on the patient's weight and on pre-treatment serum IgE IU/mL). The authors evaluated the frequency of exacerbations, the Asthma Control Test score (ACT), lung function, peripheral blood eosinophils, total IgE, and blood AF-specific IgE.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Following 6 months of <span class="elsevierStyleItalic">omalizumab</span>, improvements were observed in lung function (FEV1 68%) and the ACT changed from 21 to 25. Peripheral blood eosinophils reduced from 570/mm<span class="elsevierStyleSup">3</span> to 200/mm<span class="elsevierStyleSup">3</span>, total IgE decreased from 2286 to 1683<span class="elsevierStyleHsp" style=""></span>IU/mL. Prednisolone was reduced to 10<span class="elsevierStyleHsp" style=""></span>mg/day.</p><p id="par0035" class="elsevierStylePara elsevierViewall">After 12 months, ACT remained stable, total IgE was 1600<span class="elsevierStyleHsp" style=""></span>IU/mL, peripheral blood eosinophils decreased to 160/mm<span class="elsevierStyleSup">3</span>, AF-specific IgE raised to 60.30<span class="elsevierStyleHsp" style=""></span>kU/L. Prednisolone was stopped. FEV 1 (%) improved to 78, and a negative bronchodilator response maintained.</p><p id="par0040" class="elsevierStylePara elsevierViewall">At 18 months of treatment, total IgE was 1950<span class="elsevierStyleHsp" style=""></span>U/mL, blood eosinophils decreased to 90/mm<span class="elsevierStyleSup">3</span>, AF-specific IgE had not changed and Aspergillus precipitins were not detected. (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">There were no exacerbations or hospitalizations during the whole follow-up period.</p><p id="par0050" class="elsevierStylePara elsevierViewall">There were no adverse events reported during treatment with <span class="elsevierStyleItalic">omalizumab</span>.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The authors present the case of a patient with severe asthma and steroid-dependent ABPA who was successfully weaned from systemic steroid therapy using <span class="elsevierStyleItalic">omalizumab</span>. Corticosteroid-sparing effect of <span class="elsevierStyleItalic">omalizumab</span> is a clinically relevant finding in this case, with a major improvement in asthma symptoms and a reduction in the inflammatory markers: blood eosinophilia and total serum IgE (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). It is not known if the reduction in total serum IgE and eosinophilia is part of the natural course of ABPA or a marker for successful treatment with <span class="elsevierStyleItalic">omalizumab.</span> Lin et al.,<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> also suggest that serum IgE in patients treated with <span class="elsevierStyleItalic">omalizumab</span> is still an important marker of disease activity. Mummadj et al.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> showed that in patients with severe asthma treated with <span class="elsevierStyleItalic">omalizumab</span> serum IgE concentration may have clinically significant variability over time, affecting dosing.</p><p id="par0060" class="elsevierStylePara elsevierViewall">The time that <span class="elsevierStyleItalic">omalizumab</span> treatment has to develop a response suggests that IgE antibodies might have an important role in airflow obstruction in ABPA. The serum free IgE are reduced in a dose-dependent manner within two hours of administration of <span class="elsevierStyleItalic">omalizumab.</span></p><p id="par0065" class="elsevierStylePara elsevierViewall">In our patient a significant FEV1 improvement was achieved, with only a mild bronchial obstruction remaining. Initial studies with <span class="elsevierStyleItalic">omalizumab</span> showed that, although in patients with asthma the exacerbation rate declines during treatment, the effects on lung function remain relatively small.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> More recently, some studies have shown that anti-IgE treatment may prevent or reverse, directly and/or indirectly, airway remodelling changes.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> The effects of <span class="elsevierStyleItalic">omalizumab</span> on preventing the initiation and further propagation of the allergic inflammation cascade may explain why in our patient the improvement in the FEV1 exists, despite the relative stability after 6 months of the total IgE.</p><p id="par0070" class="elsevierStylePara elsevierViewall">In conclusion, <span class="elsevierStyleItalic">omalizumab</span> was effective in reducing exacerbations and the need for systemic corticosteroids as well as in improving asthma symptoms, in a patient with asthma and ABPA who had previously shown an unsatisfactory response to corticosteroids.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Treatment with <span class="elsevierStyleItalic">omalizumab</span> should be considered in asthmatic patients with ABPA who require prolonged use of oral steroids or have frequent relapses of the disease.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Further double-blind, randomised, placebo-controlled studies are necessary to clarify the role of anti-IgE treatment in ABPA.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">ACT<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>Asthma Control Test; AF<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Aspergillus fumigatus</span>; FEV1.0<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>forced expiratory volume in 1 second; Ig<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>immunoglobulin.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="middle" scope="col" style="border-bottom: 2px solid black">Before omalizumab \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="middle" scope="col" style="border-bottom: 2px solid black">After 6 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="middle" scope="col" style="border-bottom: 2px solid black">After 12 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="middle" scope="col" style="border-bottom: 2px solid black">After 18 months \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="middle">Eosinophils (/mm<span class="elsevierStyleSup">3</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="middle">570 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="middle">200 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="middle">160 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="middle">90 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="middle">Total IgE (IU/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="middle">2674 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="middle">1683 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="middle">1600 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="middle">1950 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="middle">AF-specific IgE (kU/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="middle">30.50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="middle">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="middle">60.30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="middle">60.30 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="middle">%FEV1.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="middle">58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="middle">68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="middle">78 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="middle">ACT score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="middle">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="middle">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="middle">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1514496.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Changes in laboratory and clinical findings after <span class="elsevierStyleItalic">omalizumab</span> treatment.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Omalizumab, an anti-immunoglobulin E antibody: state of the art" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "C. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 9 | 8 | 17 |
| 2024 October | 36 | 28 | 64 |
| 2024 September | 54 | 20 | 74 |
| 2024 August | 87 | 36 | 123 |
| 2024 July | 58 | 32 | 90 |
| 2024 June | 53 | 23 | 76 |
| 2024 May | 52 | 38 | 90 |
| 2024 April | 48 | 35 | 83 |
| 2024 March | 40 | 22 | 62 |
| 2024 February | 43 | 23 | 66 |
| 2024 January | 48 | 34 | 82 |
| 2023 December | 40 | 51 | 91 |
| 2023 November | 54 | 34 | 88 |
| 2023 October | 40 | 55 | 95 |
| 2023 September | 42 | 30 | 72 |
| 2023 August | 44 | 13 | 57 |
| 2023 July | 42 | 31 | 73 |
| 2023 June | 37 | 15 | 52 |
| 2023 May | 49 | 31 | 80 |
| 2023 April | 20 | 13 | 33 |
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