Scientific Letter
Response to Omalizumab in a Patient With Chronic Eosinophilic Pneumonia and Poor Response to Corticosteroids
Respuesta a omalizumab en paciente con neumonía eosinófila crónica y mala respuesta al tratamiento con corticoides
Eduardo Laviña-Soriano
, Ana Ampuero-López, José Luis Izquierdo-Alonso
Corresponding author
Servicio de Neumología, Hospital Universitario de Guadalajara, Guadalajara, Spain
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Poor Response to Corticosteroids" "tieneTextoCompleto" => true "saludo" => "To the Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "393" "paginaFinal" => "394" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Eduardo Laviña-Soriano, Ana Ampuero-López, José Luis Izquierdo-Alonso" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Eduardo" "apellidos" => "Laviña-Soriano" "email" => array:1 [ 0 => "jlizquierdo@sescam.org" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Ana" "apellidos" => "Ampuero-López" ] 2 => array:2 [ "nombre" => "José Luis" "apellidos" => "Izquierdo-Alonso" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Neumología, Hospital Universitario de Guadalajara, Guadalajara, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Respuesta a omalizumab en paciente con neumonía eosinófila crónica y mala respuesta al tratamiento con corticoides" ] ] "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" => 443 "Ancho" => 2333 "Tamanyo" => 100195 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Functional progress of our patient. The arrow indicates the time of starting omalizumab.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We report the case of a 55-year-old woman, former smoker since September 2012 (18 pack-years), with a history of allergic rhinoconjunctivitis and bronchial asthma. No infiltrates were observed in a chest X-ray performed in 2012. Skin prick tests showed sensitization to cat dander and grass and olive pollen.</p><p id="par0010" class="elsevierStylePara elsevierViewall">She was admitted in 2014 for an acute episode of dyspnea, breath sounds, and non-productive cough without fever. Chest X-ray revealed an alveolointersticial pattern predominantly in the lung bases. Chest computed tomography showed bilateral patchy ground glass infiltrates. Bronchoscopy was performed with transbronchial biopsy and bronchoalveolar lavage: neutrophils: 11%; eosinophils: 85.9%; lymphocytes: 0.6%. Biopsy showed a histological pattern of pulmonary eosinophilia suggestive of chronic eosinophilic pneumonia (CEP), with a focal pattern typical of organizing pneumonia. Lung function tests highlighted a restrictive pattern with carbon monoxide diffusion changes: FVC 1830 – 59%; FEV<span class="elsevierStyleInf">1</span> 1410 – 54% and FEV<span class="elsevierStyleInf">1</span>/FVC 77%. DLCO 32%; KCO 63%; TLC 61%; and RV 86%. All immunological tests were negative; IgE 493<span class="elsevierStyleHsp" style=""></span>UI/ml. In the 6-min walk test, initial saturation was 97%, distance walked 440<span class="elsevierStyleHsp" style=""></span>m, and final saturation 85%.</p><p id="par0015" class="elsevierStylePara elsevierViewall">CEP was diagnosed, with no known occupational or environmental risks, although a relationship with the administration of anti-inflammatories (celecoxib) could not be ruled out. This drug was discontinued, and treatment began with corticosteroids, resulting in both clinical and radiological worsening.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Given the poor response to treatment with corticosteroids, a surgical biopsy was performed, and the pathology study reported squamous-like interstitial pneumonia with eosinophils, consistent with CEP. The patient was placed on the lung transplantation waiting list. Lung function tests prior to the introduction of omalizumab were: FVC 1430 – 47%; FEV<span class="elsevierStyleInf">1</span> 1120 – 43%; FEV<span class="elsevierStyleInf">1</span>/FVC 78%; DLCO 24%; KCO 55%; TLC 44%; RV 81%.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In a review of the literature, 2 cases<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">1,2</span></a> of CEP with a favorable response to omalizumab were identified, so treatment began with this drug, producing clinical improvement and functional stabilization, so we decided to gradually withdraw the corticosteroids. Twenty-four months after starting omalizumab, the patient has shown a remarkable improvement in her symptoms without corticosteroids, confirming the reversal of her previous functional decline noted from the introduction of this drug (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The patient was taken off the lung transplantation waiting list when the adverse effects of steroid treatment had resolved. When mepolizumab came on the market, this therapeutic option was proposed to the patient, but she refused it in view of her good progress.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">CEP is an idiopathic disease characterized by an abnormal accumulation of eosinophils in the interstitial and alveolar space. Standard treatment is systemic corticosteroids. Response is usually so rapid and favorable, that if no response is observed, alternative diagnoses must be considered.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Our patient presented a poor response to high-dose corticosteroids, so a surgical biopsy was performed, which confirmed the initial diagnosis. We identified 2 cases of CEP with response to omalizumab in the literature<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">1,2</span></a> involving patients with elevated IgE and poor response to corticosteroids (or a requirement for high doses). In both cases, treatment with omalizumab reversed deterioration, and produced improvements in lung function tests.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Omalizumab is a humanized anti-IgE antibody, usually indicated for the treatment of persistent allergic asthma. Numerous effects that go far beyond IgE immunomodulation have also been described.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">3–11</span></a> Omalizumab reduces basophil Fc epsilon RI alfa receptor expression.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">3–5</span></a> It also induces a decrease in triptase, Th2 cytokines (IL-4 and IL-13), and chemokines (IL-8 and RANTES), irrespective of IgE levels. Similarly, it reduces cytokine expression (IL-5, IL-10, and IL-13) in dendritic cells,<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">6,7</span></a> and interferes with their ability to activate CD4. It also reduces eosinophil numbers<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">8,9</span></a> in both sputum and lung tissue, monocytes,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">9</span></a> fraction of expired nitric oxide (FENO),<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">9,10</span></a> and endothelin-1 concentrations in exhaled breath condensate.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">10</span></a> Moreover, stimulation of IgE increases the deposit of collagen I, III, and IV, and fibronectin by the Erk1/2 MAPK pathway, thereby increasing airway remodeling. By blocking this action, muscle proliferation and the deposit of pro-inflammatory substances can be reduced.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">11</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Our patient's progress not only demonstrates the favorable effect of omalizumab, but also suggests that it is more than just an IgE immunomodulator, and that its effects on eosinophilic inflammation are also important. These findings are supported by the results of basic research, and have been confirmed by reports of favorable responses, such as in our patient, in other conditions such as Churg-Strauss disease or chronic rhinosinusitis, in which eosinophilic inflammation is a key component.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">12</span></a></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Laviña-Soriano E, Ampuero-López A, Izquierdo-Alonso JL. Respuesta a omalizumab en paciente con neumonía eosinófila crónica y mala respuesta al tratamiento con corticoides. Arch Bronconeumol. 2018;54:393–394.</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" => 443 "Ancho" => 2333 "Tamanyo" => 100195 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Functional progress of our patient. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 11 | 5 | 16 |
| 2024 October | 36 | 31 | 67 |
| 2024 September | 41 | 12 | 53 |
| 2024 August | 67 | 37 | 104 |
| 2024 July | 57 | 25 | 82 |
| 2024 June | 62 | 37 | 99 |
| 2024 May | 78 | 29 | 107 |
| 2024 April | 39 | 41 | 80 |
| 2024 March | 44 | 20 | 64 |
| 2024 February | 34 | 20 | 54 |
| 2023 March | 5 | 7 | 12 |
| 2023 February | 41 | 30 | 71 |
| 2023 January | 34 | 38 | 72 |
| 2022 December | 53 | 44 | 97 |
| 2022 November | 54 | 31 | 85 |
| 2022 October | 61 | 54 | 115 |
| 2022 September | 34 | 32 | 66 |
| 2022 August | 39 | 43 | 82 |
| 2022 July | 48 | 43 | 91 |
| 2022 June | 35 | 44 | 79 |
| 2022 May | 53 | 37 | 90 |
| 2022 April | 39 | 32 | 71 |
| 2022 March | 45 | 50 | 95 |
| 2022 February | 52 | 38 | 90 |
| 2022 January | 89 | 53 | 142 |
| 2021 December | 45 | 57 | 102 |
| 2021 November | 79 | 70 | 149 |
| 2021 October | 84 | 62 | 146 |
| 2021 September | 70 | 62 | 132 |
| 2021 August | 54 | 47 | 101 |
| 2021 July | 26 | 31 | 57 |
| 2021 June | 73 | 54 | 127 |
| 2021 May | 82 | 60 | 142 |
| 2021 April | 91 | 138 | 229 |
| 2021 March | 91 | 39 | 130 |
| 2021 February | 52 | 26 | 78 |
| 2021 January | 37 | 25 | 62 |
| 2020 December | 68 | 43 | 111 |
| 2020 November | 53 | 48 | 101 |
| 2020 October | 44 | 42 | 86 |
| 2020 September | 32 | 15 | 47 |
| 2020 August | 46 | 23 | 69 |
| 2020 July | 44 | 30 | 74 |
| 2020 March | 43 | 6 | 49 |
| 2020 February | 87 | 28 | 115 |
| 2020 January | 76 | 20 | 96 |
| 2019 December | 75 | 33 | 108 |
| 2019 November | 57 | 38 | 95 |
| 2019 October | 31 | 12 | 43 |
| 2019 September | 24 | 10 | 34 |
| 2019 August | 28 | 13 | 41 |
| 2019 July | 28 | 32 | 60 |
| 2019 June | 22 | 14 | 36 |
| 2019 May | 28 | 27 | 55 |
| 2019 April | 39 | 25 | 64 |
| 2019 March | 35 | 19 | 54 |
| 2019 February | 30 | 25 | 55 |
| 2019 January | 32 | 25 | 57 |
| 2018 December | 1 | 0 | 1 |
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