NSAIDs)-exacerbated Respiratory Disease Research Articles

Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials

Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) generally have a high symptom burden and poor health-related quality of life, often requiring recurring systemic corticosteroid use and repeated sinus surgery. Dupilumab is a fully human monoclonal antibody that inhibits signalling of interleukin (IL)-4 and IL-13, key drivers of type 2 inflammation, and has been approved for use in atopic dermatitis and asthma. In these two studies, we aimed to assess efficacy and safety of dupilumab in patients with CRSwNP despite previous treatment with systemic corticosteroids, surgery, or both. LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52 were two multinational, multicentre, randomised, double-blind, placebo-controlled, parallel-group studies assessing dupilumab added to standard of care in adults with severe CRSwNP. SINUS-24 was done in 67 centres in 13 countries, and SINUS-52 was done in 117 centres in 14 countries. Eligible patients were 18 years or older with bilateral CRSwNP and symptoms despite intranasal corticosteroid use, receiving systemic corticosteroids in the preceding 2 years, or having had sinonasal surgery. Patients in SINUS-24 were randomly assigned (1:1) to subcutaneous dupilumab 300 mg or placebo every 2 weeks for 24 weeks. Patients in SINUS-52 were randomly assigned (1:1:1) to dupilumab 300 mg every 2 weeks for 52 weeks, dupilumab every 2 weeks for 24 weeks and then every 4 weeks for the remaining 28 weeks, or placebo every 2 weeks for 52 weeks. All patients were randomly assigned centrally with a permuted block randomisation schedule. Randomisation was stratified by asthma or non-steroidal anti-inflammatory drug-exacerbated respiratory disease status at screening, previous surgery at screening, and country. Patients with or without comorbid asthma were included. Coprimary endpoints were changes from baseline to week 24 in nasal polyp score (NPS), nasal congestion or obstruction, and sinus Lund-Mackay CT scores (a coprimary endpoint in Japan), done in an intention-to-treat population. Safety was assessed in a pooled population of both dupilumab groups in SINUS-52 up to week 24 and the dupilumab group in SINUS-24 and the placebo groups in both studies until week 24. The trials are complete and registered at ClinicalTrials.gov, NCT02912468 and NCT02898454. Between Dec 5, 2016, and Aug 3, 2017, 276 patients were enrolled in SINUS-24, with 143 in the dupilumab group and 133 in the placebo group receiving at least one study drug dose. Between Nov 28, 2016, and Aug 28, 2017, 448 patients were enrolled in SINUS-52, with 150 receiving at least one dose of dupilumab every 2 weeks, 145 receiving at least one dose of dupilumab every 2 weeks for 24 weeks and every 4 weeks until week 52, and 153 receiving at least one dose of placebo. Dupilumab significantly improved the coprimary endpoints in both studies. At 24 weeks, least squares mean difference in NPS of dupilumab treatment versus placebo was -2·06 (95% CI -2·43 to -1·69; p<0·0001) in SINUS-24 and -1·80 (-2·10 to -1·51; p<0·0001) in SINUS-52; difference in nasal congestion or obstruction score was -0·89 (-1·07 to -0·71; p<0·0001) in SINUS-24 and -0·87 (-1·03 to -0·71; p<0·0001) in SINUS-52; and difference in Lund-Mackay CT scores was -7·44 (-8·35 to -6·53; p<0·0001) in SINUS-24 and -5·13 (-5·80 to -4·46; p<0·0001) in SINUS-52. The most common adverse events (nasopharyngitis, worsening of nasal polyps and asthma, headache, epistaxis, and injection-site erythema) were more frequent with placebo. In adult patients with severe CRSwNP, dupilumab reduced polyp size, sinus opacification, and severity of symptoms and was well tolerated. These results support the benefits of adding dupilumab to daily standard of care for patients with severe CRSwNP who otherwise have few therapeutic options. Sanofi and Regeneron Pharmaceuticals.

Asthma Is the Dominant Factor for Recurrence in Chronic Rhinosinusitis

Factors associated with recurrence of chronic rhinosinusitis (CRS) are still poorly recognized. To evaluate which risk factors could influence the risk of recurrence among patients undergoing endoscopic sinus surgery in long-term follow-up. Patients with CRS who underwent endoscopic sinus surgery were followed for an average period of 12 years in a nonconcurrent cohort. After surgery, patients were considered to an additional endoscopic sinus surgery if appropriate medical therapy failed during this period. The presence of nasal polyps, asthma, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, smoking habits, peripheral blood eosinophilia, and atopy were assessed. The recurrence-free interval between groups (with or without these risk factors) was analyzed by Kaplan-Meyer curves, and the indication for a revisional surgery was considered to be the unfavorable event. A total of 201 patients were enrolled in this study. Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) were more likely than patients with chronic rhinosinusitis without nasal polyps (CRSsNP) to need revisional surgery (adjusted hazard ratio, 2.02). Asthma was the only factor that was significantly related to recurrence both in patients with CRSsNP (hazard ratio, 5.54) and in patients with CRSwNP (hazard ratio, 3.27). Although eosinophilia itself was not related to a higher chance of recurrence, its presence influenced the outcome of CRSwNP compared with CRSsNP and the impact of asthma among patients with CRSwNP. Prognosis in patients with CRSwNP was inferior to that in patients with CRSsNP. Asthma was the only factor that increased the chance of recurrence in patients with either CRSsNP or CRSwNP.

Hypersensitivity Reaction Due to Oral Methylprednisolone in a Patient with Nonsteroidal Anti-Inflammatory Drug-Exacerbated Respiratory Disease

Hypersensitivity reactions caused by corticosteroids are rarely seen, despite their widespread use. Sensitization with corticosteroids can occur through many routes such as nasal, aerosol, parenteral, oral and topical. Delayed allergic reactions to topically applied glucocorticoids are frequently observed but type 1 (immediate) allergic reactions to systemic glucocorticoids are very rare. When case-based publications were examined, it was noticed that corticosteroid-associated IgE-mediated type 1 hypersensitivity reactions were more common in patients with nonsteroidal antiinflammatory drug-exacerbated respiratory diseases (NERD). We present a 32-year-old patient with nonsteroidal anti-inflammatory drug-exacerbated airway disease and a hypersensitivity reaction due to methylprednisolone.

The Effect of Antileukotrienes on the Results of Postoperative Treatment of Paranasal Sinuses in Patients with Non-Steroidal Anti-Inflammatory Drug-Exacerbated Respiratory Disease

Background: Based on endoscopic examination, chronic rhinosinusitis (CRS) is divided into chronic inflammation with (CRSwNP) or without nasal polyps (CRSsNP). On the basis of the pathomechanism of inflammation, CRS is divided into endotypes. Eosinophilic CRSwNP with coexisting bronchial asthma and hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) is a real therapeutic challenge. Aim: Comparative analysis of the results of treatment of patients with CRSwNP, bronchial asthma, or hypersensitivity to NSAIDs (NSAID-exacerbated respiratory disease, NERD), using antileukotrienes (leukotriene receptor antagonists, LTRAs) or intranasal glucocorticoids or both drugs together after endoscopic sinus surgery (ESS). Material and Methods: 33 patients (11 male, 33%) with NERD divided into three groups treated with LTRAs or intranasal glucocorticoids or both drugs together were assessed in terms of general well-being, state of pathological changes, and olfactory disorders using the following tools: Sino-Nasal Outcome Test, Visual Analogue Scale, Brief Identification Smell Test, and Lund-Kennedy score before and at 12 months after surgery. CT assessments were made prior to surgery using the Lund-MacKay scale. Results: Comparable efficacy of treatment with nasal steroids and antileukotrienes was found after 12 months of observation of patients. Conclusions: The results suggest comparable efficacy of treatment with nasal steroids and antileukotrienes in patients with NERD after ESS. Treatment with montelukast and mometasone has not been shown to be superior to both drugs administered separately.

Complementary Participation of Genetics and Epigenetics in Development of NSAID-exacerbated Respiratory Disease

Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) has attracted a great deal of attention because of its association with severe asthma. However, it remains widely underdiagnosed in asthmatics as well as the general population. Upon pharmacological inhibition of cyclooxygenase 1 by NSAIDs, production of anti-inflammatory prostaglandin E2 and lipoxins ceases, while release of proinflammatory cysteinyl leukotrienes increases. To determine the underlying mechanisms, many studies have attempted to elucidate the genetic variants, such as single nucleotide polymorphisms, responsible for alterations of prostaglandins and leukotrienes, but the results of these genetic studies could not explain the whole genetic pathogenesis of NERD. Accordingly, the field of epigenetics has been introduced as an additional contributor to genomic alteration underlying the development of NERD. Recently, changes in CpG methylation, as one of the epigenetic components, have been identified in target tissues of NERD. This review discusses in silico analyses of both genetic and epigenetic components to gain a better understanding of their complementary roles in the development of NERD. Although the molecular mechanisms underlying NERD pathogenesis remain poorly understood, genetic and epigenetic variations play significant roles. Our results enhance the understanding of the genetic and epigenetic mechanisms involved in the development of NERD and suggest new approaches toward better diagnosis and management.

The GALEN rhinosinusitis cohort: chronic rhinosinusitis with nasal polyps affects health-related quality of life.

Chronic rhinosinusitis (CRS) significantly affects health-related quality of life (HRQoL). Few multinational observational studies have evaluated the impact of CRS with nasal polyps (CRSwNP) on patients’ HRQoL. This study aimed to assess HRQoL outcomes (including analyses by disease severity and impact of comorbidities and refractory disease) in CRSwNP patients from a large European database. Data were analysed from the Global Allergy and Asthma European Network (GALEN) Rhinosinusitis Cohort, including sociodemographic data, patient-reported disease severity (visual analogue scale), and scores on the 36-Item ShortForm Health Survey (SF-36) questionnaire. Differences in mean SF-36 scores were evaluated between patients with CRSwNP and population norms and between subgroups of interest (disease severity, comorbidity, and refractory disease, defined by a history of sinonasal surgery). Patients with CRSwNP (N = 445) had significantly lower mean SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores vs population norms, demonstrating that CRSwNP negatively affects HRQoL. The presence of comorbidities affected HRQoL, as shown by significant differences in PCS scores in patients with asthma or non-steroidal antiinflammatory drug-exacerbated respiratory disease, compared with patients without asthma. Patients with moderate-to-severe disease had significantly lower PCS scores than patients with mild disease. Severe disease had a significant impact on MCS score. History of surgery had a clinically meaningful negative effect on HRQoL compared with no history of surgery. CRSwNP patients have significantly lower HRQoL compared with population norms. The impact is greater in patients with greater disease severity, comorbidities, or refractory disease.

Increased expression of L‐plastin in nasal polyp of patients with nonsteroidal anti‐inflammatory drug‐exacerbated respiratory disease

Most patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD) suffer from recurrence of nasal polyps. However, little is known about the specific cellular and molecular mechanisms contributing to the pathogenesis of nasal polyp development in patients with NERD in particular, especially at baseline when cyclooxygenase 1 inhibitors are not present. The objectives of this study were to identify proteins involved in the pathogenesis of nasal polyps in patients with NERD. We collected nasal polyp tissue from patients with NERD and from patients with aspirin-tolerant chronic rhinosinusitis with nasal polyps (CRSwNP). Protein profiles were analyzed by 2-dimensional electrophoresis and identified several proteins, including L-plastin, as highly expressed. We examined L-plastin and tissue factor (TF) expression by immunohistochemical and immunofluorescence analyses. To examine the role of L-plastin in eosinophils, we knocked down L-plastin expression in Eol-1 cells by using siRNA transfection. L-plastin protein levels in nasal polyp tissue were increased in patients with NERD relative to those in patients with aspirin tolerant CRSwNP. Immunofluorescence analysis revealed that L-plastin was dominantly expressed in eosinophils and L-plastin and TF were co-expressed in eosinophils in NERD nasal polyp tissue. Knockdown of L-plastin in Eol-1 cells disrupted the cell surface distribution of TF by stimulation with granulocyte macrophage colony-stimulating factor. Increased expression of L-plastin by eosinophils may contribute to abnormal fibrin deposition through TF translocation to the eosinophil cell surface in NERD nasal polyp tissue, which in turn may contribute to the pathogenesis of NERD.

Prostaglandin E2 decrease in induced sputum of hypersensitive asthmatics during oral challenge with aspirin.

A special regulatory role for prostaglandin E2 (PGE2 ) has been postulated in nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD). To investigate the effect of systemic aspirin (acetylsalicylic acid) administration on airway PGE2 biosynthesis in induced sputum supernatant (ISS) among subjects with NERD or aspirin-tolerant asthma with chronic rhinosinusitis with nasal polyposis (ATA-CRSwNP), as well as healthy controls (HC). Induced sputum (IS) was collected from patients with NERD (n=26), ATA-CRSwNP (n=17), and HC (n=21) at baseline and after aspirin challenge. Sputum differential cell count and IS supernatant (ISS) levels of prostanoids, PGE2 , 8-iso-PGE2 , tetranor-PGE-M, 8-iso-PGF2 α, and leukotriene C4 , D4 , and E4 , were determined using mass spectrometry. Urinary excretion of LTE4 was measured by ELISA. NERD subjects had elevated sputum eosinophilic count as compared to ATA-CRSwNP and HC (median NERD 9.1%, ATA-CRSwNP 2.1%, and HC 0.4%; P<0.01). Baseline ISS levels of PGE2 were higher in asthmatics as compared to HC at baseline (NERD vs HC P=0.04, ATA-CRSwNP vs HC P<0.05). Post-challenge ISS levels of PGE2 compared to baseline significantly decreased in NERD and HC (P<0.01 and P=0.01), but not in ATA-CRSwNP. In NERD, a similar decrease in PGE2 as in HC resulted from 2.8 times lower dose of aspirin. Aspirin-precipitated bronchoconstriction is associated with a decrease in airway PGE2 biosynthesis. These results support the mechanism of PGE2 biosynthesis inhibition as a trigger for bronchoconstriction in NERD.

Chronic Rhinosinusitis-Could Phenotyping or Endotyping Aid Therapy?

We reviewed the phenotyping and endotyping of chronic rhinosinusitis (CRS) and treatment options. We searched PubMed, Google, Google Scholar, and the Proquest Central Database of the Kırıkkale University Library. Phenotypes are observable properties of an organism produced by the environment acting upon the genotype, that is, patients with a particular disorder are subgrouped according to common characteristics. Currently, CRS is usually phenotyped as being with (CRSwNP) or without (CRSsNP) nasal polyps. However, this is not immutable as some individuals progress from nonpolyp to polypoid CRS over time. Phenotypes of CRS are also based on inflammatory patterns, generally CRSwNP is eosinophilic, CRSsNP neutrophilic; but there is a spectrum, rather than a clear-cut division into 2 types. An endotype is a subtype of a condition defined by a distinct functional or pathobiological mechanism. Endotypes of CRS can be (1) nontype Th2, (2) moderate type Th2, and (3) severe type Th2 immune reactions, based on cytokines and mediators such as IL4, 5, 13. CRS endotyping can also include a (1) type 2 cytokine-based approach, (2) eosinophil-mediated approach, (3) immunoglobulin E-based approach, and (4) cysteinyl leukotriene-based approach. Subdivisions of CRSwNP can be made into nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, allergic fungal sinusitis, and eosinophil pauci-granulomatous arteritis by testing. General treatment for all CRS is nasal douching. The place of surgery needs careful reconsideration. Endotype-directed therapies include glucocorticosteroids, antibiotics, aspirin, antifungals, anticytokines, and immunoglobulin replacement. The recognition of united airways and the co-occurrence of CRSwNPs and severe asthma should lead to common endotyping of both upper and lower airways in order to better direct therapy. Endotyping can allow for the identification of groups of patients with CRS with a high likelihood of successful treatment, such as patients with a moderate type 2 immune reaction or those with acquired immune deficiency.

Nonsteroidal anti-inflammatory drug hypersensitivity in the Asia-Pacific.

Nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity reactions (HSRs) are often nonimmunologically mediated reactions which present with immediate HSR type manifestations. These are mediated by cyclooxygenase inhibition resulting in shunting towards the excessive production of leukotrienes. Important disease associations include asthma, nasal polyposis, and chronic spontaneous urticaria, especially among adults. The European Network on Drug Allergy/Global Allergy and Asthma European Network 2013 classification of NSAID HSR comprises nonselective HSR i.e., NSAID exacerbated respiratory disease (NERD), NSAIDs exacerbated cutaneous disease (NECD), NSAIDs induced urticarial-angioedema (NIUA); and selective (allergic) HSR i.e., single NSAID induced urticaria/angioedema or anaphylaxis, NSAIDs-induced delayed HSR. Much of the literature on genetic associations with NSAID HSR originate from Korea and Japan; where genetic polymorphisms have been described in genes involved in arachidonic acid metabolism, basophil/mast cell/eosinophil activation, various inflammatory mediators/cytokines, and different HLA genotypes. The Asian phenotype for NSAID HSR appears to be predominantly NIUA with overlapping features in some adults and children. NECD also appears to be more common than NERD, although both are not common in the Asian paediatric population. Between adults and children, children seem to be more atopic, although over time when these children grow up, it is likely that the prevalence of atopic adults with NSAID HSR will increase. Low-dose aspirin desensitization has been shown to be effective in the treatment of coronary artery disease, especially following percutaneous coronary intervention.

Management of Respiratory Symptoms Induced by Non-Steroidal Anti-Inflammatory Drugs

Non-steroidal anti-inflammatory drugs (NSAIDs)-exacerbated respiratory disease (NERD) is defined by the combination of chronic rhinosinusitis, nasal polyps, bronchial asthma, and hypersensitivity reactions involving upper and/or lower airways after the exposure to acetylsalicylic acid (ASA) and other NSAIDs. However, airway inflammation occurs even in the absence of exposure to these drugs, leading to disease progression with aggressive polyp formation and non-optimal controlled asthma and rhinosinusitis. In this review, we discuss current and potential management strategies of NERD. This management should be multidisciplinary and comprise medical and surgical treatment of the underlying diseases. In order to prevent reactions due to NSAIDs, avoidance of COX-1 inhibitors with provision of safe therapeutic alternatives should be indicated. However, avoidance of NSAIDs does not ensure disappearance of the airway inflammation and this progresses and persists for life. ASA desensitization followed by daily ASA therapy remains the gold standard of NERD treatment. It is indicated in patients with uncontrolled bronchial and nasal symptoms as well as in patients who require NSAID treatment for specific diseases, such as rheumatic or cardiovascular conditions. ASA desensitization improves upper and lower respiratory symptoms, reduces the need for new nasal surgeries and increases quality of life. Different ASA desensitization protocols have been reported, although the addition of intranasal ketorolac and lysine aspirin prior to an oral ASA schedule has made ASA desensitization safer and more efficient. New therapeutic strategies are being investigated and may provide an alternative treatment for those patients in which ASA desensitization are contraindicated or continuous ASA therapy is discontinued because of adverse effects. Among them, biologic agents are an important treatment option, useful for controlling symptoms of the upper and lower airways. More investigation studies into the mechanisms involved in NERD are needed in order to identify additional therapeutic targets.

Identification of phenotypic clusters of nonsteroidal anti-inflammatory drugs exacerbated respiratory disease.

Clinical presentation of nonsteroidal anti-inflammatory drugs exacerbated respiratory disease (NERD) is found to be heterogeneous. This study classified phenotypic clusters to determine NERD subtypes. We performed two-step cluster analysis using urticaria, chronic rhinosinusitis (CRS), and atopy, in a NERD cohort comprising 302 patients. Asthma exacerbation was defined as receiving at least one burst of intravenous steroid treatment and/or at least two bursts of oral steroid use (≥ 45 mg/3 days) per year. The possession rate of anti-asthmatic medications was estimated during the follow-up period. There were four subtypes: subtype 1 (NERD with CRS/atopy and no urticaria), subtype 2 (NERD with CRS and no urticaria/atopy), subtype 3 (NERD without CRS/urticaria), and subtype 4 (NERD with urticaria). Significant differences were found between the four subtypes in the female proportion, baseline FEV1%, serum total IgE level, and sputum/peripheral eosinophil count. A higher frequency of asthma exacerbations was noted in subtype 1 compared to subtype 3. The possession rates of medium- to high-dose inhaled corticosteroids/long-acting beta2 -agonists showed significant differences among the four subtypes. Metabolomic analysis showed that the four subtypes of NERD had a higher serum leukotriene E4 (LTE4) level than those with aspirin-tolerant asthma. The patients with subtypes 1 and 3 had a higher urine LTE4 level than those with subtype 2. We found four distinct subtypes with different clinical/biochemical findings and asthma exacerbations in a NERD cohort. These findings suggest that stratified strategies by applying subtype classification may help achieve better outcomes in the management of NERD.

Asthma and Rhinitis Induced by Selective Immediate Reactions to Paracetamol and Non-steroidal Anti-inflammatory Drugs in Aspirin Tolerant Subjects.

In subjects with non-steroidal anti-inflammatory drugs (NSAIDs)- exacerbated respiratory disease (NERD) symptoms are triggered by acetyl salicylic acid (ASA) and other strong COX-1 inhibitors, and in some cases by weak COX-1 or by selective COX-2 inhibitors. The mechanism involved is related to prostaglandin pathway inhibition and leukotriene release. Subjects who react to a single NSAID and tolerate others are considered selective responders, and often present urticaria and/or angioedema and anaphylaxis (SNIUAA). An immunological mechanism is implicated in these reactions. However, anecdotal evidence suggests that selective responders who present respiratory airway symptoms may also exist. Our objective was to determine if subjects might develop selective responses to NSAIDs/paracetamol that manifest as upper/lower airways respiratory symptoms. For this purpose, we studied patients reporting asthma and/or rhinitis induced by paracetamol or a single NSAID that tolerated ASA. An allergological evaluation plus controlled challenge with ASA was carried out. If ASA tolerance was found, we proceeded with an oral challenge with the culprit drug. The appearance of symptoms was monitored by a clinical questionnaire and by measuring FEV1 and/or nasal airways volume changes pre and post challenge. From a total of 21 initial cases, we confirmed the appearance of nasal and/or bronchial manifestations in ten, characterized by a significant decrease in FEV1% and/or a decrease in nasal volume cavity after drug administration. All cases tolerated ASA. This shows that ASA tolerant subjects with asthma and/or rhinitis induced by paracetamol or a single NSAID without skin/systemic manifestations exist. Whether these patients represent a new clinical phenotype to be included within the current classification of hypersensitivity reactions to NSAIDs requires further investigation.

Nonsteroidal anti-inflammatory drug (NSAID) exacerbated respiratory disease phenotype: Topical NSAID and asthma control – A possible oversight link

BackgroundPatients with aspirin-exacerbated respiratory disease (AERD) also recently known as nonsteroidal anti-inflammatory drug (NSAID) exacerbated respiratory disease (NERD) must avoid aspirin and all other oral NSAIDs. The effect of topical NSAID (tNSAID), especially salicylates which are commonly present in topical medicated preparations, on asthma control of this phenotype is studied. MethodsThe study inclusion criteria were adults with: 1) NSAID hypersensitivity; 2) nasal polyposis/chronic rhinosinusitis; 3) not well-/poorly controlled asthma and 4) exposure to tNSAID. Patients were given verbal and written instructions to cease tNSAIDs exposure and asthma control was evaluated during the 6 months prior and after intervention. ResultsThere were eleven patients (ten females) with a mean age of 56.5 (range 37–71) years. Prior known oral NSAIDs hypersensitivity included aspirin (5), mefenamic acid (2), diclofenac (2), Synflex (2) and ibuprofen (1). All, except 2, had arthropathies or spinal disorders and were using tNSAID for a mean of 4.2 years. One, four and six patients were using over-the-counter medicated oil containing salicylates, NSAID gel/plasters and both respectively. All patients had cutaneous, with 4 having concomitant inhalational exposure to these tNSAIDs. The mean duration of asthma diagnosis and uncontrolled asthma were 25.2 and 4.5 years respectively. Except for 2 patients, there was no change in asthma maintenance medications pre and post-intervention. Asthma control significantly (p < 0.05) improved based on pre and post-intervention ACT score, number of exacerbations, FEV1 were 14.9 and 22.1, 1.9 and 0.43, 1.28L and 1.67L respectively. ConclusionsIt is paramount to eliminate not only oral but topical NSAID exposure in NERD phenotype asthmatic patients. When a long-standing asthma progressed to uncontrolled, a meticulous evaluation of tNSAIDs exposure is warranted especially if the patient has developed chronic pain.

Clinical benefits of aspirin desensitization in patients with nonsteroidal anti-inflammatory drug exacerbated respiratory disease are not related to urinary eicosanoid release and are accompanied with decreased urine creatinine.

Treatment with acetylsalicylic acid (ASA) after desensitization may be a therapeutic option in patients with nonsteroidal anti-inflammatory drug exacerbated respiratory disease (NERD). The mechanisms that lead to improvement in rhinosinusitis and asthma symptoms remain unknown. To attribute the documented clinical effects of ASA treatment of chronic rhinosinusitis and/or asthma to the release of eicosanoid metabolites in urine. Fourteen patients with NERD were successfully desensitized, and, eventually, eight patients were treated with 650 mg of ASA daily for 3 months. In addition to clinical assessments, nuclear magnetic resonance imaging and smell test were performed before and after treatment with ASA. Venous blood and urine were collected before desensitization and after 1 and 3 months of treatment. The levels of urinary leukotrienes (LT) (cysteinyl LT and LTE4) and tetranor PGDM (metabolite of prostaglandin D2) were measured by enzyme-linked immunosorbent assay. Treatment with ASA after desensitization alleviated symptoms of rhinosinusitis, improved nasal patency (mean, 50% decrease in peak nasal inspiratory flow) and sense of smell (fourfold increase in smell test score) in as early as 4 weeks. Clinical improvements were not accompanied by any change in sinonasal mucosa thickness as assessed with nuclear magnetic resonance. Urinary cysteinyl LTs, LTE4, and prostaglandin D2 metabolite remained relatively stable during ASA treatment and did not correlate with clinical improvements. Desensitization was associated with a progressive decrease of urinary creatinine. Clinical improvement in rhinosinusitis and/or asthma after ASA desensitization was not related to concentrations of urinary eicosanoid metabolites. A decrease of urinary creatinine requires further study to determine the renal safety of long-term treatment with ASA after desensitization.

Hypersensitivity to Aspirin and other NSAIDs: Diagnostic Approach in Patients with Chronic Rhinosinusitis.

Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) associated with chronic rhinosinusitis (CRS) and/or asthma comprises a distinct clinical syndrome referred to as NSAIDs exacerbated respiratory disease (NERD). Patients with NERD tend to have more severe course of both upper (CRS and nasal polyps) and lower airway (asthma) diseases and are usually recalcitrant to conventional treatment modalities. Diagnosing and phenotyping of patients with NERD are critical for prevention of drug-induced adverse reactions and open novel options for management of underlying chronic airway inflammatory diseases. Diagnosis of NERD is based on detailed clinical history confirmed by challenge with aspirin, but new diagnostic approaches are currently being developed. This review article focuses on the diagnostic approach to a patient with CRS and hypersensitivity to NSAIDs, emphasizing the importance of diagnosis for proper patient’s management.

Nonsteroidal anti-inflammatory drugs-exacerbated respiratory disease in adolescents.

There has been no study investigating nonsteroidal anti-inflammatory drugs (NSAIDs)-exacerbated respiratory disease (NERD) exclusively in childhood. Therefore, in the current study, the authors aimed to evaluate the diagnostic features, clinical characteristics, and follow-up of adolescents diagnosed with NERD. The patients who were consecutively diagnosed with NERD between January 2011, and November 2013, included in the study. Oral provocation test (OPT) with at least 2 different NSAIDs was used to confirm NSAID hypersensitivity in patients with underlying asthma/chronic rhinosinusitis/nasal polyps. All patients were followed regularly in 3-month intervals by the Pediatric Allergy and Otorhinolaryngology Department for asthma, allergic rhinitis, or chronic rhinosinusitis with or without nasal polyps. A total of 10 adolescents with NERD were included in the study. The mean age of the patients at the time of diagnosis was 14.9 ± 1.5 years. Hives or angioedema accompanied respiratory complaints induced by NSAIDs. The mean duration of follow-up was 28.9 ± 12.4 months. All patients had asthma except 1 with asymptomatic bronchial hyperreactivity. Asthma of patients was well-controlled with moderate dose of inhaled corticosteroids. Chronic rhinosinusitis with or without nasal polyps developed in 2 patients. Aspirin desensitization was required in these 2 patients with recurrent nasal polyps. NERD in childhood has much more favorable clinical characteristics and course than in adulthood. Few adolescents with NERD refer with typical chronic upper respiratory tract complaints. The asthma component seems to be mild and is well controlled in the short-term follow-up.