Scientific Letter
Non-IgE-mediated Asthma After Zinc Exposure
Asma inmunológica no mediada por IgE tras exposición ocupacional a cinc
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Letter</span>" "titulo" => "Non-IgE-mediated Asthma After Zinc Exposure" "tieneTextoCompleto" => true "saludo" => "To the Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "346" "paginaFinal" => "347" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Angelica Leal, Irene Caselles, Maria Jesús Rodriguez-Bayarri, Xavier Muñoz" "autores" => array:4 [ 0 => array:3 [ "nombre" => "Angelica" "apellidos" => "Leal" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Irene" "apellidos" => "Caselles" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Maria Jesús" "apellidos" => "Rodriguez-Bayarri" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:4 [ "nombre" => "Xavier" "apellidos" => "Muñoz" "email" => array:1 [ 0 => "xmunoz@vhebron.net" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 3 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Servicio de Neumología, Hospital Vall d’Hebron, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Mutua Asepeyo, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "CIBER de enfermedades respiratorias (CIBERes), Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Departament de Biologia Ce·lular, Fisiologia i d’Immunologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Asma inmunológica no mediada por IgE tras exposición ocupacional a cinc" ] ] "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" => 831 "Ancho" => 1368 "Tamanyo" => 54481 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Result of specific bronchial provocation test with zinc. A late-onset reduction in FEV<span class="elsevierStyleInf">1</span> of 23% from baseline was observed after inhalation of zinc sulfate at a concentration of 0.1<span class="elsevierStyleHsp" style=""></span>mg/ml for 5<span class="elsevierStyleHsp" style=""></span>min, requiring administration of a ß2-agonist (B2).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Various metals have been described as causing occupational asthma (OA), mostly chromium, nickel, and cobalt. The mechanism of action by which these metals can produce OA is generally immunological, either IgE-mediated or not.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">1,2</span></a> To date, only 2 cases of OA caused by zinc have been described, and in both cases, an IgE-dependent mechanism was involved in the pathogenesis of the disorder.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We describe, for the first time, a worker exposed to zinc who developed OA via a non-IgE-mediated immunological mechanism. Our patient was a 30-year-old man, former smoker of 5 pack-years, whose only clinical history consisted of a diagnosis of bronchial asthma in childhood, which had remitted, and for which he had not required treatment for 15 years. He had been working for 4 years as an industrial mechanic, making metal parts, and was in regular contact with copper, cadmium, zinc, and manganese dust. The patient consulted due to a 5-month history of cough, expectoration, wheezing, and dyspnea. Symptoms appeared some time after start of exposure and improved during the weekends and periods of sick leave. He had had to attend the emergency department on 5 occasions since the onset of symptoms. Chest radiograph was normal. Clinical laboratory tests showed a total IgE of 140<span class="elsevierStyleHsp" style=""></span>kU/l. Skin tests for airborne allergens were positive for house dust mites, while contact skin tests for metal, including nickel sulfate, potassium dichromate, cadmium, cobalt chloride, and zinc 2.5%, were negative. Forced spirometry showed FVC 6360<span class="elsevierStyleHsp" style=""></span>ml (112%), FEV<span class="elsevierStyleInf">1</span> 4390<span class="elsevierStyleHsp" style=""></span>ml (98%), and FEV<span class="elsevierStyleInf">1</span>/FVC 69%. A methacholine challenge was positive with a PC<span class="elsevierStyleInf">20</span> of 4<span class="elsevierStyleHsp" style=""></span>mg/ml. A provocation test was performed, according to standard methodology for testing metals,<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">1,5</span></a> for which concentrations of 0.1<span class="elsevierStyleHsp" style=""></span>mg/ml, 1<span class="elsevierStyleHsp" style=""></span>mg/ml, and 10<span class="elsevierStyleHsp" style=""></span>mg/ml of zinc sulfate were prepared. The 0.1<span class="elsevierStyleHsp" style=""></span>mg/ml solution was nebulized for a total of 5<span class="elsevierStyleHsp" style=""></span>min, split into periods of 1, 2, and 2<span class="elsevierStyleHsp" style=""></span>min. Four hours after exposure, a 23% reduction in FEV<span class="elsevierStyleInf">1</span> from baseline was observed (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), along with cough, wheezing, and dyspnea. These symptoms abated after administration of a ß2 agonist. Ten hours after exposure, the patient presented the same symptoms, with a 29% reduction in FEV<span class="elsevierStyleInf">1</span>, requiring administration of intravenous corticosteroids in addition to ß2 agonist, and a 12-h stay in the emergency department.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Clinical and lung function data suggested that the patient had zinc-related OA, mediated by a non-IgE-dependent immunological mechanism. This diagnosis was supported by the latency period before the onset of symptoms after initiation of exposure, late onset of symptoms during the working day, the negative specific IgE test and skin tests, and the late reaction after the provocation test. Indeed, 2 recent studies have shown that low molecular weight agents are usually associated with late-onset reactions in which, although the immunological mechanisms are unclear, a non-IgE-dependent immunological mechanism is likely if no early or dual reaction is observed.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">6,7</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Currently, OA is classified as immunological and non-immunological or irritant-induced, the most representative form being reactive airways dysfunction syndrome.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">8</span></a> Immunological OA is further subdivided into IgE-mediated and non-IgE-mediated, depending on its physiopathological origin.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">9</span></a> Although low molecular weight agents can cause immunological OA by both mechanisms, the IgE-mediated mechanism is generally exceptional, while a non-IgE-mediated mechanism is more common; this is the case with isocyanates and persulfates.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">10</span></a> However, the situation appears to differ when OA is caused by exposure to metals, in which some authors report that a non-IgE-mediated mechanism is observed in only 30%–40% of patients.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">1</span></a> In the specific case of zinc, the 2 cases reported to date suggested an IgE-mediated mechanism, as an early response was observed in the specific bronchial provocation test (SBPT), with a reduction in FEV<span class="elsevierStyleInf">1</span> of 23% and 28% 10 and 20<span class="elsevierStyleHsp" style=""></span>min after inhalation, respectively.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">3,4</span></a> In this context, our observation supports the notion that, while there is no evidence of zinc sensitization, it must be considered as a possible causative agent of OA, and this diagnosis must not be ruled out. It is also important to mention that the presence of asthma before the occupational exposure, such as the childhood asthma reported by our patient, does not exclude the OA diagnosis, if the presence of an immunological mechanism (IgE or otherwise) is shown between exposure to the causative agent and the patient's asthma.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">11</span></a> In our case, this mechanism was confirmed by the provocation test.</p><p id="par0025" class="elsevierStylePara elsevierViewall">It is also interesting to note that the patient's asthma presented clinically as severe, reflected by his attending the emergency department on 5 occasions during the 5-month period between the onset of asthma and diagnosis. The severe asthmatic reaction presented by the patient during the provocation test, requiring him to remain in the emergency department for 12<span class="elsevierStyleHsp" style=""></span>h, is also remarkable. Moreover, this reaction occurred after exposure to 0.1<span class="elsevierStyleHsp" style=""></span>mg/ml of zinc sulfate, a concentration not previously associated with severe asthmatic reactions in provocation tests with metals.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">5,12–14</span></a> In the 2 cases of OA caused by zinc reported to date, the reaction occurred when doses of 1 and 10<span class="elsevierStyleHsp" style=""></span>mg/ml, respectively were used, and no severe reactions were observed.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">3,4</span></a> This observation is in line with the evidence of Meca et al.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">7</span></a> who suggested that when low molecular weight agents act by non-IgE-mediated mechanisms, the asthma can be more severe.</p><p id="par0030" class="elsevierStylePara elsevierViewall">In conclusion, this case shows that zinc can cause OA by a non-IgE-mediated mechanism, and that this diagnosis must not be excluded when specific IgE and contact skin tests are negative. We also stress the possibility that asthma caused by this agent can be particularly severe, and recommend caution when performing the SBPT.</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: Leal A, Caselles I, Rodriguez-Bayarri MJ, Muñoz X. Asma inmunológica no mediada por IgE tras exposición ocupacional a cinc. Arch Bronconeumol. 2017;53:346–347.</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" => 831 "Ancho" => 1368 "Tamanyo" => 54481 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Result of specific bronchial provocation test with zinc. A late-onset reduction in FEV<span class="elsevierStyleInf">1</span> of 23% from baseline was observed after inhalation of zinc sulfate at a concentration of 0.1<span class="elsevierStyleHsp" style=""></span>mg/ml for 5<span class="elsevierStyleHsp" style=""></span>min, requiring administration of a ß2-agonist (B2).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:14 [ 0 => array:3 [ "identificador" => "bib0075" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "[in Spanish]" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Occupational asthma caused by chromium and nickel" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M.J. Cruz" 1 => "R. Costa" 2 => "E. Marquilles" 3 => "F. Morell" 4 => "X. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 2 | 7 |
| 2024 October | 42 | 24 | 66 |
| 2024 September | 44 | 15 | 59 |
| 2024 August | 61 | 49 | 110 |
| 2024 July | 52 | 16 | 68 |
| 2024 June | 69 | 30 | 99 |
| 2024 May | 75 | 27 | 102 |
| 2024 April | 55 | 35 | 90 |
| 2024 March | 47 | 13 | 60 |
| 2024 February | 32 | 26 | 58 |
| 2023 March | 2 | 2 | 4 |
| 2023 February | 46 | 16 | 62 |
| 2023 January | 27 | 33 | 60 |
| 2022 December | 58 | 43 | 101 |
| 2022 November | 41 | 26 | 67 |
| 2022 October | 42 | 39 | 81 |
| 2022 September | 38 | 29 | 67 |
| 2022 August | 30 | 57 | 87 |
| 2022 July | 29 | 36 | 65 |
| 2022 June | 33 | 33 | 66 |
| 2022 May | 33 | 31 | 64 |
| 2022 April | 27 | 23 | 50 |
| 2022 March | 35 | 33 | 68 |
| 2022 February | 38 | 26 | 64 |
| 2022 January | 44 | 38 | 82 |
| 2021 December | 34 | 41 | 75 |
| 2021 November | 49 | 45 | 94 |
| 2021 October | 61 | 42 | 103 |
| 2021 September | 37 | 44 | 81 |
| 2021 August | 32 | 51 | 83 |
| 2021 July | 40 | 41 | 81 |
| 2021 June | 106 | 33 | 139 |
| 2021 May | 47 | 43 | 90 |
| 2021 April | 103 | 86 | 189 |
| 2021 March | 41 | 23 | 64 |
| 2021 February | 25 | 23 | 48 |
| 2021 January | 29 | 18 | 47 |
| 2020 December | 27 | 16 | 43 |
| 2020 November | 23 | 15 | 38 |
| 2020 October | 47 | 17 | 64 |
| 2020 September | 67 | 15 | 82 |
| 2020 August | 27 | 12 | 39 |
| 2020 July | 22 | 27 | 49 |
| 2020 June | 29 | 11 | 40 |
| 2020 May | 17 | 8 | 25 |
| 2020 April | 23 | 13 | 36 |
| 2020 March | 29 | 11 | 40 |
| 2020 February | 33 | 15 | 48 |
| 2020 January | 31 | 13 | 44 |
| 2019 December | 22 | 25 | 47 |
| 2019 November | 33 | 17 | 50 |
| 2019 October | 18 | 6 | 24 |
| 2019 September | 27 | 12 | 39 |
| 2019 August | 33 | 15 | 48 |
| 2019 July | 27 | 16 | 43 |
| 2019 June | 18 | 9 | 27 |
| 2019 May | 37 | 21 | 58 |
| 2019 April | 21 | 19 | 40 |
| 2019 March | 42 | 26 | 68 |
| 2019 February | 24 | 20 | 44 |
| 2019 January | 19 | 6 | 25 |
| 2018 December | 16 | 15 | 31 |
| 2018 November | 43 | 16 | 59 |
| 2018 October | 62 | 18 | 80 |
| 2018 September | 14 | 8 | 22 |
| 2018 May | 16 | 1 | 17 |
| 2018 April | 14 | 4 | 18 |
| 2018 March | 15 | 4 | 19 |
| 2018 February | 19 | 5 | 24 |
| 2018 January | 26 | 11 | 37 |
| 2017 December | 30 | 12 | 42 |
| 2017 November | 22 | 7 | 29 |
| 2017 October | 18 | 9 | 27 |
| 2017 September | 29 | 13 | 42 |
| 2017 June | 1 | 2 | 3 |
| 2017 April | 0 | 1 | 1 |
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