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

ABSTRACT: 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.

SUBMITTER: Makowska J

PROVIDER: S-EPMC4493793 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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

Makowska Joanna J Lewandowska-Polak Anna A Kowalski Marek L ML

Current allergy and asthma reports 20150801 8

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 ...[more]

PMID: 26149590

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Project description:RationaleThe mechanisms that underlie the pathogenesis of chronic rhinosinusitis without nasal polyps (CRSsNP), chronic rhinosinusitis with nasal polyps (CRSwNP), and aspirin-exacerbated respiratory disease (AERD) are not clear.ObjectivesTo first evaluate the inflammatory profiles of CRSsNP and CRSwNP tissues and then to investigate whether clinical differences observed between CRSwNP and AERD are in part secondary to differences in inflammatory mediator expression within nasal polyp (NP) tissues.MethodsExpression levels of numerous inflammatory mediators were determined by quantitative real-time polymerase chain reaction, ELISA, and multiplex immunoassay.Measurements and main resultsCRSwNP NP had increased levels of type 2 mediators, including IL-5 (P < 0.001), IL-13 (P < 0.001), eotaxin-2 (P < 0.001), and monocyte chemoattractant protein (MCP)-4 (P < 0.01), compared with sinonasal tissue from subjects with CRSsNP and control subjects. Expression of IFN-? messenger RNA or protein was low and not different among the chronic rhinosinusitis subtypes examined. Compared with CRSwNP, AERD NP had elevated protein levels of eosinophil cationic protein (ECP) (P < 0.001), granulocyte-macrophage colony-stimulating factor (GM-CSF) (P < 0.01), and MCP-1 (P = 0.01), as well as decreased gene expression of tissue plasminogen activator (tPA) (P = 0.02). Despite the higher eosinophilia in AERD, there was no associated increase in type 2 mediator protein levels observed.ConclusionsCRSwNP was characterized by a predominant type 2 inflammatory environment, whereas CRSsNP did not reflect a classic type 1 milieu, as has been suggested previously. AERD can be distinguished from CRSwNP by elevated ECP levels, but this enhanced eosinophilia is not associated with elevations in traditional type 2 inflammatory mediators associated with eosinophil proliferation and recruitment. However, other factors, including GM-CSF, MCP-1, and tPA, may be important contributors to AERD pathogenesis.

Project description:Non-steroidal anti-inflammatory drugs (NSAIDs)-induced hypersensitivity reactions are classified by the European Network on Drug Allergy (ENDA) as either cross-reactive or selective. The former is the most frequent type and includes patients with exclusively respiratory symptoms (NSAIDs-exacerbated respiratory disease, NERD) or exclusively cutaneous symptoms: NSAIDs-induced urticaria/angioedema (NIUA); and NSAIDs-exacerbated cutaneous disease (NECD). However, although not reflected in the current classification scheme (ENDA), in clinical practice a combination of both skin and respiratory symptoms or even other organs such as gastrointestinal tract symptoms (mixed or blended reactions) is frequently observed. This entity has not been sufficiently characterised. Our aim was to clinically characterize blended reactions to NSAIDs, comparing their clinical features with NERD and NIUA. We evaluated patients with symptoms suggestive of hypersensitivity to NSAIDs who attended the Allergy Unit of the Regional University Hospital of Malaga (Malaga, Spain) between 2008 and 2015. We included 880 patients confirmed as cross-reactive based on clinical history, positive nasal provocation test with lysine acetylsalicylate (NPT-LASA), and/or positive drug provocation test (DPT) with acetylsalicylic acid (ASA), who were classified as blended (261; 29.6%), NERD (108; 12.3%) or NIUA (511; 58.1%). We compared symptoms, drugs, underlying diseases and diagnostic methods within and between groups. Among blended patients the most common sub-group comprised those developing urticaria/angioedema plus rhinitis/asthma (n?=?138), who had a higher percentage of underlying rhinitis (p?<?0.0001) and asthma (p?<?0.0001) than NIUA patients, showing similarities to NERD. These differences were not found in the sub-group of blended patients who developed such respiratory symptoms as glottis oedema; these were more similar to NIUA. The percentage of positive NPT-LASA was similar for blended (77%) and NERD groups (78.7%). We conclude that blended reactions are hypersensitivity reactions to NSAIDs affecting at least two organs. In addition to classical skin and respiratory involvement, in our population a number of patients also develop gastrointestinal symptoms. Given the high rate of positive responses to NPT-LASA in NERD as well as blended reactions, we suggest that all patients reporting respiratory symptoms, regardless of whether they have other associated symptoms, should be initially evaluated using NPT-LASA, which poses less risk than DPT.

Project description:BackgroundMicroparticles (MPs) are submicron-sized shed membrane vesicles released from activated or injured cells and are detectable by flow cytometry. MP levels have been used as biomarkers to evaluate cell injury or activation in patients with pathological conditions.ObjectiveWe sought to compare MP types and levels in nasal lavage fluids (NLFs) from controls and patients with chronic rhinosinusitis without nasal polyps (CRSsNP), chronic rhinosinusitis with nasal polyps (CRSwNP), and aspirin-exacerbated respiratory disease (AERD).MethodsWe collected NLFs from patients with CRSsNP (n = 33), CRSwNP (n = 45), and AERD (n = 31) and control (n = 24) subjects. Standardized flow cytometry methods were used to characterize the following MP types: endothelial MPs, epithelial MPs (epithelial cell adhesion molecule [EpCAM](+)MPs, E-cadherin(+)MPs), platelet MPs (CD31(+)CD41(+)MPs), eosinophil MPs (EGF-like module-containing mucin-like hormone receptor-like 1[EMR1](+)MPs), mast cell MPs (high-affinity IgE receptor [FcεRI](+)c-kit(+)MPs), and basophil MPs (CD203c(+)c-kit(-)MPs). Basophil activation was evaluated by the mean fluorescence intensity of CD203c on basophil MPs.ResultsActivated mast cell MPs (CD137(+) FcεRI(+)c-kit(+)MPs) were significantly increased in NLFs of controls compared with NLFs of patients with CRSsNP (2.3-fold; P < .02), CRSwNP (2.3-fold; P < .03), and AERD (7.4-fold; P < .0001). Platelet MPs (3.5-fold; P < .01) and basophil MPs (2.5-fold; P < .05) were increased only in patients with AERD. Mean fluorescence intensity of CD203c on MPs was increased in patients with CRSwNP (P < .002) and AERD (P < .0001), but not in patients with CRSsNP. EpCAM(+)MPs in patients with CRSwNP were no different from control (P = .91) and lower than those in patients with CRSsNP (P < .02) and AERD (P < .002).ConclusionsBased on released MPs, mast cells, platelets, and basophils were more highly activated in patients with AERD than in patients with CRS. Epithelial injury was lower in patients with CRSwNP than in patients with CRSsNP and AERD. MP analysis may help identify phenotypes of CRS, and in distinguishing AERD from CRSwNP.

Dataset Information

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

Publications

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

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