Scientific Letter
Successful Long-Term Treatment Combining Omalizumab and Anti-IL-5 Biologics in Allergic Bronchopulmonary Aspergillosis
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array:23 [ "pii" => "S0300289622000011" "issn" => "03002896" "doi" => "10.1016/j.arbres.2021.12.005" "estado" => "S300" "fechaPublicacion" => "2022-08-01" "aid" => "2974" "copyright" => "SEPAR" "copyrightAnyo" => "2022" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Arch Bronconeumol. 2022;58:624-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:17 [ "pii" => "S0300289622000849" "issn" => "03002896" "doi" => "10.1016/j.arbres.2022.01.013" "estado" => "S300" "fechaPublicacion" => "2022-08-01" "aid" => "3015" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Arch Bronconeumol. 2022;58:627-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "An Euler Proportional Venn Diagram of Obstructive Lung Disease" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "627" "paginaFinal" => "628" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1930 "Ancho" => 2917 "Tamanyo" => 274873 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Population proportionality of obstructive lung disease. (a) Nonproportional Venn diagram of COPD showing subsets of patients with chronic bronchitis, emphysema, and asthma. Reprinted with permission from the American Thoracic Society.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> (b) Euclidean Proportional Venn diagram of OLD in the United States (NHANES III surveys from 1988 to 1994) and United Kingdom (GPRD 1998) for all ages. Reprinted with permission from Chest.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> (c) Euler Proportional Venn diagram of OLD for all ages in the United States (NHANES III surveys from 1988 to 1994). (d) Euler Proportional Venn diagram of OLD for all ages in United Kingdom (GPRD 1998). Footnote: In Fig. 1a the subsets comprising COPD are shaded. Subset areas are not proportional to the actual relative subset sizes. Asthma is by definition associated with reversible airflow obstruction, although in variant asthma special maneuvers may be necessary to make the obstruction evident. Patients with asthma whose airflow obstruction is completely reversible (i.e., subset 9) are not considered to have COPD. Because in many cases it is virtually impossible to differentiate patients with asthma whose airflow obstruction does not remit completely from persons with chronic bronchitis and emphysema who have partially reversible airflow obstruction with airway hyperreactivity, patients with unremitting asthma are classified as having COPD (i.e., subsets 6, 7, and 8). Chronic bronchitis and emphysema with airflow obstruction usually occur together (subset 5), and some patients may have asthma associated with these two disorders (i.e., subset 8). Individuals with asthma who have been exposed to chronic irritation, as from cigarette smoke, may develop chronic productive cough, which is a feature of chronic bronchitis (i.e., subset 6). Such patients often are referred to in the United States as having asthmatic bronchitis or the asthmatic form of COPD. Persons with chronic bronchitis and/or emphysema without airflow obstruction (i.e., subsets 1, 2, and 11) are not classified as having COPD. Patients with airway obstruction due to diseases with known etiology or specific pathology, such as cystic fibrosis or obliterative bronchiolitis (subset 10), are not included in this definition.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Joan B. Soriano, Xiaochen Dai, Julio Ancochea" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Joan B." "apellidos" => "Soriano" ] 1 => array:2 [ "nombre" => "Xiaochen" "apellidos" => "Dai" ] 2 => array:2 [ "nombre" => "Julio" "apellidos" => "Ancochea" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289622000849?idApp=UINPBA00003Z" "url" => "/03002896/0000005800000008/v2_202301240755/S0300289622000849/v2_202301240755/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S030028962100380X" "issn" => "03002896" "doi" => "10.1016/j.arbres.2021.11.005" "estado" => "S300" "fechaPublicacion" => "2022-08-01" "aid" => "2944" "copyright" => "SEPAR" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Arch Bronconeumol. 2022;58:621-3" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:9 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "Safety and Feasibility of Transbronchial Cryobiopsy in Mechanically Ventilated Patients" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "621" "paginaFinal" => "623" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Alfons Torrego, Ana M. Muñoz-Fernández, Carmen Mª Lucena, Pedro Castro, Laura López-Vilaró, Joan Ramón Badía, Antoni Betbesé, Josep Ramirez, Felipe Andreo, María-Teresa Fernández-Figueras, Marc Fabra-Radua, Virginia Pajares, Carles Agustí" "autores" => array:13 [ 0 => array:2 [ "nombre" => "Alfons" "apellidos" => "Torrego" ] 1 => array:2 [ "nombre" => "Ana M." "apellidos" => "Muñoz-Fernández" ] 2 => array:2 [ "nombre" => "Carmen Mª" "apellidos" => "Lucena" ] 3 => array:2 [ "nombre" => "Pedro" "apellidos" => "Castro" ] 4 => array:2 [ "nombre" => "Laura" "apellidos" => "López-Vilaró" ] 5 => array:2 [ "nombre" => "Joan Ramón" "apellidos" => "Badía" ] 6 => array:2 [ "nombre" => "Antoni" "apellidos" => "Betbesé" ] 7 => array:2 [ "nombre" => "Josep" "apellidos" => "Ramirez" ] 8 => array:2 [ "nombre" => "Felipe" "apellidos" => "Andreo" ] 9 => array:2 [ "nombre" => "María-Teresa" "apellidos" => "Fernández-Figueras" ] 10 => array:2 [ "nombre" => "Marc" "apellidos" => "Fabra-Radua" ] 11 => array:2 [ "nombre" => "Virginia" "apellidos" => "Pajares" ] 12 => array:2 [ "nombre" => "Carles" "apellidos" => "Agustí" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S030028962100380X?idApp=UINPBA00003Z" "url" => "/03002896/0000005800000008/v2_202301240755/S030028962100380X/v2_202301240755/en/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "Successful Long-Term Treatment Combining Omalizumab and Anti-IL-5 Biologics in Allergic Bronchopulmonary Aspergillosis" "tieneTextoCompleto" => true "saludo" => "To the Director," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "624" "paginaFinal" => "626" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Daniel Laorden, Ester Zamarrón, Javier Domínguez-Ortega, David Romero, Santiago Quirce, Rodolfo Álvarez-Sala" "autores" => array:6 [ 0 => array:4 [ "nombre" => "Daniel" "apellidos" => "Laorden" "email" => array:1 [ 0 => "daniel.laorden@salud.madrid.org" ] "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" => "Ester" "apellidos" => "Zamarrón" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Javier" "apellidos" => "Domínguez-Ortega" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "David" "apellidos" => "Romero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Santiago" "apellidos" => "Quirce" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 5 => array:3 [ "nombre" => "Rodolfo" "apellidos" => "Álvarez-Sala" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Pneumology, Universidad Autónoma, Madrid, La Paz University Hospital, IdiPAZ, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Allergy, La Paz University Hospital, IdiPAZ, and CIBER of Respiratory Diseases, CIBERES, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2250 "Ancho" => 2167 "Tamanyo" => 207349 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">ACT: Asthma Control Test; EOS: eosinophils; FEV1: forced expiratory volume in 1 second; ER: exacerbation rate; IgE: immunoglobulin E (UI/ml)*; IL5: interleukin 5; IL5R: interleukin 5 receptor. FEV1 was calculated in a MasterScreen spirometer (Viasys, Würzburg, Germany) according to ATS/ERS recommendations and GLI reference values for spirometry. * IgE levels measured during treatment with omalizumab concern free and omalizumab-bound IgE.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">16</span></a></p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Allergic bronchopulmonary aspergillosis (ABPA) is considered a T2 inflammatory disease caused by a hypersensitivity reaction to <span class="elsevierStyleItalic">Aspergillus fumigatus</span> (AF) fungal spores. It affects up to 2.5% of patients with persistent asthma and is diagnosed using recommended criteria.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">1</span></a> ABPA pathogenesis is a combination of innate and adaptive allergic immune responses. It is driven by T2 interleukins (ILs), such as IL4 and IL13 cytokines, which activate immunoglobulin<span class="elsevierStyleCrossOut">e</span>-E (IgE)-secreting plasmocytes and promote eosinophilic attraction and IL5 secretion.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Standard treatment includes oral corticosteroids (OCS) and itraconazole.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">1</span></a> Despite this treatment, some patients continue to experience uncontrolled asthma symptoms. The effectiveness of omalizumab and anti-IL5/IL5 receptor (IL5R) in ABPA has been documented in case reports and case series.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">3–10</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">We present for the first time the results of a long-term combination of omalizumab and anti-IL5/IL5R in 3 patients treated for severe asthma and ABPA over 2 years.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Case 1 is a 67-year-old man who was diagnosed with allergic asthma. He was treated with inhaled corticosteroids (ICs) (budesonide 320<span class="elsevierStyleHsp" style=""></span>mcg/12<span class="elsevierStyleHsp" style=""></span>h) and formoterol. His asthma progressively worsened, with 2 exacerbations that required hospitalisation needing prednisone (10<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h) in a maintenance regimen. At that time, a complete study showed a positive skin prick test for AF, and blood tests revealed eosinophilia (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), high total IgE (1457<span class="elsevierStyleHsp" style=""></span>IU/ml) and elevated specific AF-IgE (16.3<span class="elsevierStyleHsp" style=""></span>kU/L). Computed tomography (CT) showed central bronchiectasis with mucoid impactions in both lower lobes. There were no other concomitant allergic diseases. The patient was thus diagnosed with ABPA.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">1</span></a> Treatment was modified to budesonide (1600 mcg per day), formoterol, tiotropium, montelukast, prednisone (1<span class="elsevierStyleHsp" style=""></span>mg/kg/d) and itraconazole (200<span class="elsevierStyleHsp" style=""></span>mg daily). After 2 months of treatment, prednisone could not be reduced below 7.5<span class="elsevierStyleHsp" style=""></span>mg.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">In an attempt to reduce OCS, omalizumab (at recomended doses adjusted to IgE level and weight) was prescribed. Over 5 years, his asthma symptoms and exacerbations were controlled, and OCS could be reduced to 2.5<span class="elsevierStyleHsp" style=""></span>mg daily.</p><p id="par0030" class="elsevierStylePara elsevierViewall">After this period, the patient progressively needed slightly higher doses of OCS to maintain control of daily symptoms, and he experienced 2 exacerbations and elevated blood eosinophils (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), that required increased doses of OCS to 5<span class="elsevierStyleHsp" style=""></span>mg (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). We added benralizumab 30<span class="elsevierStyleHsp" style=""></span>mg/q4w, and q8w after 3 doses. This combined treatment controlled the exacerbations for 1 year and OCS could be supressed, and the total IgE was reduced (610<span class="elsevierStyleHsp" style=""></span>IU/ml). Thus, we decided to reduce the omalizumab doses to 225<span class="elsevierStyleHsp" style=""></span>mg/q2w. One year later, the patient's symptoms remain well controlled without daily OCS and with no exacerbations (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Case 2 is a 74-year-old woman diagnosed with allergic asthma. Initially, her asthma was controlled with ICs (fluticasone propionate 500 mcg) and salmeterol; 5 years later, however, her asthma control worsened, with at least 4 exacerbations.</p><p id="par0040" class="elsevierStylePara elsevierViewall">A skin prick test revealed sensitisation to AF, and a blood test showed eosinophilia (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), high total IgE (2619<span class="elsevierStyleHsp" style=""></span>IU/ml) and elevated specific AF-IgE (96.1<span class="elsevierStyleHsp" style=""></span>kU/L). CT demonstrated central bilateral bronchiectasis with mucoid impactions. She suffered no other allergic comorbidities. Taking all these data into account, the patient was diagnosed with ABPA.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">1</span></a> Treatment was intensified: fluticasone propionate was increased up to 1000<span class="elsevierStyleHsp" style=""></span>mcg/day and tiotropium was added, as well as prednisone (1<span class="elsevierStyleHsp" style=""></span>mg/kg/d) and oral itraconazole (200<span class="elsevierStyleHsp" style=""></span>mg/d).</p><p id="par0045" class="elsevierStylePara elsevierViewall">After 2 months of treatment, even with prednisone 5<span class="elsevierStyleHsp" style=""></span>mg daily to control asthma symptoms, she experienced 2 exacerbations needing OCS. Therefore, omalizumab was started (at recomended doses adjusted to IgE level and weight), which managed to control her asthma and withdrawn OCS for 9 years.</p><p id="par0050" class="elsevierStylePara elsevierViewall">After this period, the patient had 2 exacerbations, worsening of daily symptoms and eosinophilia (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Then, we started her on benralizumab 30<span class="elsevierStyleHsp" style=""></span>mg/q4w, and q8w after 3 doses.</p><p id="par0055" class="elsevierStylePara elsevierViewall">After 1 year of follow-up, she reported an improvement in symptoms and had no exacerbations. Given that total IgE had been reduced to 770<span class="elsevierStyleHsp" style=""></span>IU/ml, we decided to reduce omalizumab to 225<span class="elsevierStyleHsp" style=""></span>mg/q2w. One year later, she remains asymptomatic.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Case 3 is a 51-year-old man diagnosed with allergic asthma. He was receiving treatment with ICs (fluticasone propionate 1000 mcg) and salmeterol.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Five years later, he had 2 severe exacerbations. A skin prick test for AF was positive, and a blood test revealed eosinophilia (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), elevated total IgE (1206<span class="elsevierStyleHsp" style=""></span>IU/ml) and elevated specific AF-IgE (18.1<span class="elsevierStyleHsp" style=""></span>kU/L). CT showed central bronchiectasis and mucoid impaction in the left superior lobe. A diagnosis of ABPA was made.</p><p id="par0070" class="elsevierStylePara elsevierViewall">The patient was given treatment with prednisone (1<span class="elsevierStyleHsp" style=""></span>mg/kg/day), itraconazole (200<span class="elsevierStyleHsp" style=""></span>mg/d) and inhaled tiotropium. Given that there was no clinical improvement (he had 3 exacerbations) and because it was not possible to withdraw OCS, omalizumab at recomended doses adjusted to IgE level and weight was prescribed. One year later, his symptoms had improved<span class="elsevierStyleCrossOut">,</span> and exacerbations stopped; thus, OCS could be reduced to 5<span class="elsevierStyleHsp" style=""></span>mg daily.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Three years later, he had 3 exacerbations, and eosinophils increased (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Mepolizumab 100<span class="elsevierStyleHsp" style=""></span>mg/q4w was initiated. It led to control of the exacerbations, and OCS was tapered 1 year later. Total IgE was reduced to 682<span class="elsevierStyleHsp" style=""></span>IU/ml. At this time, we reduced the omalizumab dose to 150<span class="elsevierStyleHsp" style=""></span>mg/q2w; 1 year later, symptoms remain controlled.</p><p id="par0080" class="elsevierStylePara elsevierViewall">This group of patients with severe asthma and ABPA improved after being treated with maximum doses of omalizumab. A few years later, however, they experienced unexpected clinical deterioration. Suspecting the involvement of an eosinophil-driven inflammatory pathway, we added anti-IL5/IL5R therapy.</p><p id="par0085" class="elsevierStylePara elsevierViewall">We added anti-IL5/IL5R therapy to omalizumab and maintain the latter because it was initially effective in controlling symptoms (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), preventing exacerbations and tapering OCS (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>) for several years. Combining omalizumab and anti-IL5/IL5R allowed us to control symptoms (Asthma Control Test, ACT: 20–24), reduce exacerbations to zero, improve pulmonary function (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) and taper OCS (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). This improvement in ABPA control allowed us to step down progressively the dose of omalizumab, therefore reducing costs. This process is still going on, and may allow us to reduce it even more in the future, to the minimun effective dose.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Treating both allergic and eosinophilic pathways could be an effective and safe way to control refractory ABPA and spare OCS. Although the effectiveness of combining omalizumab and anti-IL5/IL5R in ABPA has been documented in case reports,<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">11,12</span></a> given that we do not know whether the same effect would be observed if omalizumab had been switched entirely for anti-IL5/IL5R, further mechanistic studies are needed.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Regarding safety, it is relevant that these patients did not present any adverse events during treatment, including bacterial or parasitic infections. There is no evidence in the literature of any adverse events from combining omalizumab with anti-IL5/R.<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">11–15</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">In conclusion, our results suggest that adding an IL-5/IL5R biologic on top of omalizumab offers the opportunity to control symptoms in patients with severe asthma and ABPA with a partial response to omalizumab.</p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Ethics</span><p id="par0105" class="elsevierStylePara elsevierViewall">The research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. Information revealing the patient's identity has been avoided. All patients have been identified by numbers or aliases and not by their real names.</p><p id="par0110" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Study approval statement</span>: Ethics approval was not required because it was a retrospective and observational study. We did not change our daily clinical practice.</p><p id="par0115" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Consent to publish statement</span>: The study participants have given their written informed consent to publish their case (including publication of images).</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Funding</span><p id="par0120" class="elsevierStylePara elsevierViewall">No funding has been received for this study.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Conflicts of interest</span><p id="par0125" class="elsevierStylePara elsevierViewall">None.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Ethics" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "Funding" ] 2 => array:2 [ "identificador" => "sec0020" "titulo" => "Conflicts of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2250 "Ancho" => 2167 "Tamanyo" => 207349 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">ACT: Asthma Control Test; EOS: eosinophils; FEV1: forced expiratory volume in 1 second; ER: exacerbation rate; IgE: immunoglobulin E (UI/ml)*; IL5: interleukin 5; IL5R: interleukin 5 receptor. FEV1 was calculated in a MasterScreen spirometer (Viasys, Würzburg, Germany) according to ATS/ERS recommendations and GLI reference values for spirometry. * IgE levels measured during treatment with omalizumab concern free and omalizumab-bound IgE.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">16</span></a></p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1408 "Ancho" => 2501 "Tamanyo" => 162662 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Timeline of prednisone use (mg/day) during treatment of 3 cases. 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| Year/Month | Html | Total | |
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