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Long-term clinical effects of aspirin-desensitization therapy among patients with poorly controlled asthma and non-steroidal anti-inflammatory drug hypersensitivity: An exploratory study
a Department of Otorhinolaryngology, Campus Virchow, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
b Department of Otorhinolaryngology, Campus Mitte, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 13353 Berlin, Germany
c Department of Allergy and Pulmonology, Johanniterstrasse 1, 14929 Treuenbrietzen, Germany
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Förster-Ruhrmann, S.-M. Zappe, A.J. Szczepek, H. Olze, U. Rabe" "autores" => array:5 [ 0 => array:4 [ "nombre" => "U." "apellidos" => "Förster-Ruhrmann" "email" => array:1 [ 0 => "ulrike.foerster@charite.de" ] "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" => "S.-M." "apellidos" => "Zappe" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "A.J." "apellidos" => "Szczepek" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "H." 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"apellidos" => "Rabe" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Department of Otorhinolaryngology, Campus Virchow, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Otorhinolaryngology, Campus Mitte, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 13353 Berlin, Germany" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Department of Allergy and Pulmonology, Johanniterstrasse 1, 14929 Treuenbrietzen, Germany" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2295 "Ancho" => 3210 "Tamanyo" => 453154 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Asthma medication parameters before and after acetylsalicylic acid (ASA) desensitization therapy ((a) asthma medication of stable asthma patients; (b) asthma medication of instable asthma patients and (c) corticoiddosages of asthma patients).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Asthma is a global respiratory health problem affecting 1-18% of the population in different countries.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> According to the Global Initiative for Asthma (GINA), the levels of asthma symptom control can be divided into controlled, partially controlled and uncontrolled asthma forms.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Intolerance to non-steroidal anti-inflammatory drugs (NSAIDs) can be detected among 13–21% of the asthmatics.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> For the asthmatics with nasal polyps (NP), the incidence of NSAIDs intolerance increases to 30%.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> This association has been termed as “aspirin triad”, “aspirin-exacerbated respiratory disease” (AERD) or “NSAIDs hypersensitivity”.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a> The pathogenesis of the AERD is based on a shift from eicosanoids to leukotrienes.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Depending in its severity, asthma can be treated with beta-2 mimetics, corticosteroids, leukotriene receptor antagonists, theophylline or anti-IgE antibodies.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> A further therapeutic option for asthmatics and NSAIDs hypersensitivity is the aspirin desensitization,<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> where the patient is gradually introduced step by step to aspirin, and a daily maintenance dose is determined. The underlying mechanism of aspirin desensitization has until today not yet been completely clarified. Interestingly, following desensitization, there is an increase in the prostaglandin PGE<span class="elsevierStyleInf">2</span>/leukotriene index in patients’ blood.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> To the best of our knowledge, clinical effects of aspirin desensitization in patients with a poorly controlled asthma and NSAIDs hypersensitivity have not yet been reported. For this reason, the aim of our study was to investigate the outcome of aspirin desensitization in patients with NSAIDs hypersensitivity and a poorly controlled asthma. We performed comparative analyses using the data obtained from the patients with controlled asthma and NSAIDs hypersensitivity who underwent aspirin therapy.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Methods</span><p id="par0010" class="elsevierStylePara elsevierViewall">Patients routinely desensitized against at least 18 months in the Department of Pulmonology (Treuenbrietzen, Germany) or the ORL Department of the Charité University Hospital (Berlin) between 2009 and 2013 were included in this retrospective study. All patients enrolled in the study gave their informed consent. The inclusion criteria were NSAIDs sensitivity, nasal polyps, controlled or poorly controlled asthma.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Twelve patients (mean age 48 y, range from 32 y to 73 y, 4 men, 8 women) with poorly controlled asthma and 20 patients with controlled asthma (mean age 57.75 y, range from 44 y to 67 y, 8 men, 12 women) were included. The “poorly controlled asthma”-group consisted of ten patients with uncontrolled asthma and two patients with partially controlled asthma. Aspirin was recommended to be taken by both groups, in order to improve the nasal and asthma symptoms.</p><p id="par0020" class="elsevierStylePara elsevierViewall">NSAIDs sensitivity was confirmed by oral aspirin provocation test; a positive reaction was a decline of forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s (FEV1)<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>20% of baseline and profound rhinorrhea or nasal blockage.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> The patients were stepwise desensitized to oral aspirin in the hospital with a final daily aspirin maintenance dosage of 500<span class="elsevierStyleHsp" style=""></span>mg. The following desensitization protocol was used: day 1: placebo/placebo/placebo; day 2: 1/2/4/8; day 3: 10/20/40/80; day 4: 100/100/150; day 5: 200/200/500; from day 6: 500<span class="elsevierStyleHsp" style=""></span>mg orally administered aspirin.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Following parameters were evaluated:</p><p id="par0030" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Levels of asthma symptom control</span>: Assessment of symptom control was done by strictly following the GINA criteria<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> – see <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Following groups of patients were identified:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1.</span><p id="par0035" class="elsevierStylePara elsevierViewall">Controlled or stable asthma group: well controlled asthma;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2.</span><p id="par0040" class="elsevierStylePara elsevierViewall">Poorly controlled or instable asthma group: partially controlled asthma/uncontrolled asthma.</p></li></ul></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Pulmonary function values</span>: The peak expiratory flow (PEF) variability was measured before aspirin desensitization. The forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s (FEV1) and vital capacity (VC) were measured by spirometry before and following aspirin treatment.</p><p id="par0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Use of asthma medication</span>: The daily use and dosages of the asthma medication were documented. The daily dosages of inhaled corticoids (ICS low/medium/high dosage) and the asthma medication scores were obtained in accordance to GINA criteria.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Prednisolone-dependent patients were separated from the dual GINA classification of severity. The medication was not changed 6 months prior to desensitization.</p><p id="par0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Nasal endoscopy</span>: The Davos-staging of nasal polyps (NP) size was performed (0: no NP; 1: NP in middle meatus; 2: NP beyond middle meatus; 3: obstructing NP).<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Sense of smell</span>: The subjective olfactory function was semi-quantitatively documented (0: no sense of smell; 1: mild sense of smell; 2: moderate sense of smell; 3: excellent sense of smell).</p><p id="par0065" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Follow-up</span>: The patients were routinely examined before aspirin therapy, 6, 12 and 18 months (visit 1, 2 and 3) following aspirin therapy. Pulmonary and nasal parameters were documented.</p><p id="par0070" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Adverse events</span>: Adverse events during aspirin induction and maintenance therapy were documented.</p><p id="par0075" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Statistics</span>: A nonparametric test of independent samples (Mann–Whitney <span class="elsevierStyleItalic">U</span> test) was used to test the spirometric parameters FEV-1 and VC, asthma medication and the nasal polyps between patient groups. The levels of asthma control and smell were tested with the chi-squared test (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05).</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Results</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Patients’ characterization prior to aspirin desensitization therapy</span><p id="par0080" class="elsevierStylePara elsevierViewall">The mean FEV1-, VC values were significantly lower and PEF variability values higher in the poorly controlled asthma patients (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01). The nasal polyps size did not differ significantly (0.55/0.95; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.21). The asthma medication score in poorly controlled asthma patients was significantly higher than in the controlled group (4.25/2.20, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01).</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Patients with poorly controlled asthma following aspirin desensitization therapy</span><p id="par0085" class="elsevierStylePara elsevierViewall">In relation to the symptoms of the asthma control levels four patients (33.3%) still had uncontrolled asthma and eight patients controlled asthma after 6 months (67%). After 12 months of aspirin therapy 11 patients had controlled asthma (91.7%) and one patient with uncontrolled asthma, which finally improved to partially controlled asthma after 18 months. The asthma control level of all visits following aspirin therapy improved significantly when compared to the baseline, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01. The mean FEV1 values increased from the initial 67.4% to 82.4% after 12 months (<span class="elsevierStyleItalic">p</span> 0.03). The VC values increased from the initial 83.9% to 87.8% (<span class="elsevierStyleItalic">p</span> 1.00), the size of nasal polyps from initial 0.33 to 0.50 (<span class="elsevierStyleItalic">p</span> 0.56). The sense of smell improved significantly after 18 months from 1.85 to 2.25 (<span class="elsevierStyleItalic">p</span> 0.02) (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>). The asthma medication score declined from 4.2 to 3.9 (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.18).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Patients with controlled asthma following aspirin desensitization therapy</span><p id="par0090" class="elsevierStylePara elsevierViewall">No patient developed uncontrolled asthma during the follow-up examination. The mean FEV values were 92% before and 92.4% following therapy, the VC values 101.6% before and 96.3% following aspirin desensitization (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>0.50). The nasal polyps scores decreased (0.95/0.65; <span class="elsevierStyleItalic">p</span> 1.00). The sense of smell improved from 1.50 to 2.15 (<span class="elsevierStyleItalic">p</span> 0.16), the sense of smell scores improved significantly after 12 months (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.03) (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>). The asthma medication level in this group was constant 2.2 (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.00).</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Comparison of the poorly controlled and the controlled asthma patients following 18 months of aspirin therapy</span><p id="par0095" class="elsevierStylePara elsevierViewall">After 18 months, the FEV1 values and the size of nasal polyps did not differ significantly between the patient groups, the VC values from the poorly controlled asthma group were significantly lower (84.4%/93.5%; <span class="elsevierStyleItalic">p</span> 0.03). In addition, the medication score was still significantly elevated in the poorly controlled asthma group (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01).</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Examination of corticosteroid-dependent patients</span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Patient group with controlled asthma and oral prednisolone</span><p id="par0105" class="elsevierStylePara elsevierViewall">One patient was on permanent oral 10<span class="elsevierStyleHsp" style=""></span>mg prednisolone. The mean FEV1 value decreased from initial 72% to 69%, the nasal polyp size increased from 0 to 2 after 18 months aspirin therapy.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Patient group with uncontrolled asthma and oral prednisolone</span><p id="par0120" class="elsevierStylePara elsevierViewall">Prior to desensitization, four patients were on permanent oral prednisolone (mean dosage 13.3<span class="elsevierStyleHsp" style=""></span>mg). After 18 months therapy one patient had partial controlled asthma and the other patients had controlled asthma. The mean prednisolone dosage was reduced to 6.5<span class="elsevierStyleHsp" style=""></span>mg (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). The mean FEV1 value increased from 60% to 97% and the nasal polyp size from 0 to 0.67.</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Patient group with uncontrolled asthma and intravenous prednisolone</span><p id="par0130" class="elsevierStylePara elsevierViewall">One patient had an asthma exacerbation before aspirin therapy and was treated with an intravenous prednisolone pulse therapy (initial dosage 250<span class="elsevierStyleHsp" style=""></span>mg). The FEV1 was 46% and the nasal polyp size 0. After 18 months of aspirin desensitization, the asthma was controlled, FEV1 was 89% and the nasal polyp size 0. Parenteral prednisolone therapies were not repeated.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Adverse events</span><p id="par0135" class="elsevierStylePara elsevierViewall">In three patients with poorly controlled asthma, administration of aspirin induced recurrent asthma attacks. These patients were initially administered 150<span class="elsevierStyleHsp" style=""></span>mg or 300<span class="elsevierStyleHsp" style=""></span>mg aspirin. During the second desensitization appointment, the dosage of aspirin has been increased to 500<span class="elsevierStyleHsp" style=""></span>mg, which induced no complications. During the maintenance therapy, no adverse events were observed.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0140" class="elsevierStylePara elsevierViewall">This retrospective study demonstrates for the first time that the patients with a NSAIDs-hypersensitivity and poorly controlled asthma can benefit from aspirin desensitization. Following 6 months desensitization, the asthma control levels significant improved. In epidemiological studies, the asthma severity in NDAIDs hypersensitive patients was higher and FEV1 values lower, as compared to NSAIDs tolerant asthma patients.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,13</span></a> In both studies, aspirin therapy was not performed. The pathomechanism of the NSAIDs hypersensitivity is based on an altered cyclooxygenase metabolism.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> The effect of aspirin desensitization is not yet really clear. Under the daily aspirin administration, a significant increase of the prostaglandin E<span class="elsevierStyleInf">2</span>/leukotriene index<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> appears to take place.</p><p id="par0145" class="elsevierStylePara elsevierViewall">According to GINA criteria, the main goal of asthma management is to gain optimal asthma control.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Depending on the severity of the disease, a multimodal therapy involving beta-2-mimetics, corticosteroids, leukotriene receptor antagonists, and theophylline or anti-IgE antibodies is necessary. Dahlén et al. examined the effects of leukotriene receptor antagonist montelukast in NSAIDs-hypersensitive patients and found significantly improved FEV1 values.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Some patients in our study were treated with montelukast (see <a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). Since no changes in medication were made, our results appear to be aspirin-dependent.</p><p id="par0150" class="elsevierStylePara elsevierViewall">Berges Gimeno examined 126 patients (daily 1300<span class="elsevierStyleHsp" style=""></span>mg aspirin) and registered over one year a significant reduction of nasal symptoms and a significant reduction in the number of short-term prednisolone treatments due to asthma.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> In our study the oral prednisolone dosage was reduced from the original mean 13.3<span class="elsevierStyleHsp" style=""></span>mg to mean 6.5<span class="elsevierStyleHsp" style=""></span>mg in instable asthma patients. One instable asthma patient who received intravenous prednisolone during asthma exacerbation prior to aspirin desensitization, no longer needed corticosteroids after desensitization. In the work of Stevenson, inclusion criteria for the aspirin desensitization required a FEV1 variability of <10% and FEV1 values of >60%.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> In our study, we included patients with PEF variability greater than 10% (instable asthma 45%; stable asthma 14%). The mean FEV1 values in our sample were better than Stevensons’ inclusion criteria (instable asthma 67%; stable asthma 92%). We demonstrated that the FEV1 values significantly improved in the poorly controlled asthma patients following 12 months of aspirin therapy (<span class="elsevierStyleItalic">p</span> 0.03). Also, the FEV1 values of corticosteroid-dependent patients increased following aspirin therapy in our study (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><p id="par0155" class="elsevierStylePara elsevierViewall">Havel et al. found that 56 patients with NSAIDs hypersensitivity receiving aspirin for more than 18 months (daily 500<span class="elsevierStyleHsp" style=""></span>mg aspirin) following nasal sinus surgery have improved in relation to asthma and nasal complaints.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> The spirometric examinations were not done in follow-up. A significantly lower nasal polyp size in patients receiving aspirin was observed, as compared to the patients not receiving aspirin. In our study, the difference in nasal polyp size before and after aspirin therapy was not significant, which may depend on our inclusion criteria, where we did not compare nasal polyp groups with and without aspirin desensitization therapy and our patients were not all included immediately after surgery.</p><p id="par0160" class="elsevierStylePara elsevierViewall">Therapy of patients with therapy-resistant asthma and NSAIDs hypersensitivity requires a multimodal therapeutic concept according to pulmonary guidelines. To the best of our knowledge, the present study is the first retrospective examination of patients with NSAIDs hypersensitivity and poorly controlled asthma receiving aspirin therapy. Concerning the asthma symptom control levels, a significant improvement was observed (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01). Although the patients certainly profit from the asthma medication administered according to GINA guidelines, they can also profit from an add-on aspirin therapy. Further studies with larger samples are necessary to further validate this therapy. This exploratory retrospective analysis will be continued in order to compare NSAIDs sensitive asthmatic patients subjected to NSAIDs desensitization with the patients receiving standard therapy.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Ethical disclosures</span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Protection of human and animal subjects</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Confidentiality of data</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data.</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Right to privacy and informed consent</span><p id="par0205" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article.</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Author contribution</span><p id="par0175" class="elsevierStylePara elsevierViewall">UFR: conceived the study, performed patients examinations, collected and interpreted the data and wrote the manuscript.</p><p id="par0180" class="elsevierStylePara elsevierViewall">SM.Z: performed patients examinations and collected the data.</p><p id="par0185" class="elsevierStylePara elsevierViewall">AJ.S: interpreted the data and wrote the manuscript.</p><p id="par0190" class="elsevierStylePara elsevierViewall">HO: supervised the project, interpreted the data and wrote the manuscript.</p><p id="par0195" class="elsevierStylePara elsevierViewall">UR: conceived the study, performed patients examinations, supervised the project and wrote the manuscript.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflict of interest</span><p id="par0200" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres634656" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec647184" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xpalclavsec647185" "titulo" => "Abbreviations" ] 3 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 4 => array:2 [ "identificador" => "sec0010" "titulo" => "Methods" ] 5 => array:3 [ "identificador" => "sec0015" "titulo" => "Results" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Patients’ characterization prior to aspirin desensitization therapy" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Patients with poorly controlled asthma following aspirin desensitization therapy" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Patients with controlled asthma following aspirin desensitization therapy" ] 3 => array:2 [ "identificador" => "sec0035" "titulo" => "Comparison of the poorly controlled and the controlled asthma patients following 18 months of aspirin therapy" ] 4 => array:3 [ "identificador" => "sec0070" "titulo" => "Examination of corticosteroid-dependent patients" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0075" "titulo" => "Patient group with controlled asthma and oral prednisolone" ] 1 => array:2 [ "identificador" => "sec0080" "titulo" => "Patient group with uncontrolled asthma and oral prednisolone" ] 2 => array:2 [ "identificador" => "sec0085" "titulo" => "Patient group with uncontrolled asthma and intravenous prednisolone" ] ] ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Adverse events" ] ] ] 6 => array:2 [ "identificador" => "sec0045" "titulo" => "Discussion" ] 7 => array:3 [ "identificador" => "sec0050" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0090" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0095" "titulo" => "Right to privacy and informed consent" ] ] ] 8 => array:2 [ "identificador" => "sec0060" "titulo" => "Author contribution" ] 9 => array:2 [ "identificador" => "sec0065" "titulo" => "Conflict of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-09-24" "fechaAceptado" => "2015-06-05" "PalabrasClave" => array:1 [ "en" => array:2 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec647184" "palabras" => array:8 [ 0 => "Asthma" 1 => "Levels of asthma symptom control" 2 => "GINA" 3 => "Uncontrolled asthma" 4 => "Aspirin-exacerbated respiratory disease (AERD)" 5 => "NSAIDs hypersensitivity" 6 => "NSAIDs sensitive asthma" 7 => "Nasal polyps" ] ] 1 => array:4 [ "clase" => "abr" "titulo" => "Abbreviations" "identificador" => "xpalclavsec647185" "palabras" => array:15 [ 0 => "AERD" 1 => "ASA" 2 => "FEV1" 3 => "GINA" 4 => "ICS" 5 => "LABA" 6 => "Mo" 7 => "NP" 8 => "NSAIDs" 9 => "PEF" 10 => "SABA" 11 => "VC" 12 => "V1" 13 => "V2" 14 => "V3" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">According to the Global Initiative for Asthma (GINA), the levels of asthma symptom control can be divided into controlled, partially controlled and uncontrolled asthma. Optional therapy for non-steroidal anti-inflammatory drugs (NSAIDs)-hypersensitive asthmatics uses aspirin desensitization, but until now, this therapy is not established in difficult to treat cases. The aim of this study was to evaluate the efficacy of aspirin desensitization in patients with poorly controlled asthma.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Patients with poorly controlled asthma, NDAIDs hypersensitivity and aspirin desensitization were included in the retrospective study. The data were compared to those obtained from patients with controlled asthma and aspirin therapy. Lung function, levels of asthma symptom control, asthma medication, the size of nasal polyps (NP) and smell function were evaluated over 18 months.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Thirty-two patients were included in the study (uncontrolled/partially controlled asthma <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>12; controlled asthma <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>20). After 18 months of follow-up, the patients with poorly controlled asthma had significantly increased forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s (FEV1) values, as compared to the baseline (66–82%; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.02), the levels of asthma control improved significantly (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01). The asthma medication was reduced. In the group of controlled asthma the FEV1 values did not increase significantly (91.9–92.4%; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.05) and the asthma medication was constant. In relation to nasal parameters the sense of smell improved significantly in both groups, NP-scores did not differ significantly.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Patients with a poorly controlled asthma and NSAIDs hypersensitivity profit from an add-on aspirin therapy.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2366 "Ancho" => 2649 "Tamanyo" => 369611 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Pulmonary function values before and after acetylsalicylic acid (ASA) desensitization therapy ((a) Vital capacity (VC) values; (b) forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s (FEV1) values; (c) asthma control levels (1: uncontrolled; 2: partial controlled; 3: controlled) and (d) FEV1 values of prednisolone dependent patients).</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1148 "Ancho" => 2441 "Tamanyo" => 138190 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Nasal parameters before and after acetylsalicylic acid (ASA) desensitization therapy ((a) Nasal polyps and (b) smell ability).</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2295 "Ancho" => 3210 "Tamanyo" => 453154 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Asthma medication parameters before and after acetylsalicylic acid (ASA) desensitization therapy ((a) asthma medication of stable asthma patients; (b) asthma medication of instable asthma patients and (c) corticoiddosages of asthma patients).</p>" ] ] 3 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "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 " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Asthma symptom control</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Levels of asthma symptom control</th></tr><tr title="table-row"><th class="td" title="table-head " colspan="3" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">In the past 4 weeks, has the patient had</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Well controlled \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Partially controlled \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Uncontrolled \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="top">Day time asthma<br>Symptoms more than twice/week \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes□ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No□ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="4" align="left" valign="top">None of these</td><td class="td" title="table-entry " rowspan="4" align="left" valign="top">1–2 of these</td><td class="td" title="table-entry " rowspan="4" align="left" valign="top">3–4 of these</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Any night waking due to asthma? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes□ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No□ \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="top">Reliever needed for symptoms more than twice/week \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes□ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No□ \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="top">Any activity limitation due to asthma? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes□ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No□ \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1041286.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">GINA assessment of asthma symptom control.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:17 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Global Initiative for Asthma (GINA)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Global Strategy for Asthma Management and Prevention" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "2014" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The frequency of hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) in the population of adult asthmatics in Poland based on an epidemiological questionnaire" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "L. 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| Year/Month | Html | Total | |
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| 2024 November | 8 | 10 | 18 |
| 2024 October | 25 | 29 | 54 |
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