Diagnosis and management of NSAID‐Exacerbated Respiratory Disease (N‐ERD)—a EAACI position paper

Abstract

NSAID-exacerbated respiratory disease (N-ERD) is a chronic eosinophilic, inflammatory disorder of the respiratory tract occurring in patients with asthma and/or chronic rhinosinusitis with nasal polyps (CRSwNP), symptoms of which are exacerbated by NSAIDs, including aspirin. Despite some progress in understanding of the pathophysiology of the syndrome, which affects 1/10 of patients with asthma and rhinosinusitis, it remains a diagnostic and therapeutic challenge. In order to provide evidence-based recommendations for the diagnosis and management of N-ERD, a panel of international experts was called by the EAACI Asthma Section. The document summarizes current knowledge on the pathophysiology and clinical presentation of N-ERD pointing at significant heterogeneity of this syndrome. Critically evaluating the usefulness of diagnostic tools available, the paper offers practical algorithm for the diagnosis of N-ERD. Recommendations for the most effective management of a patient with N-ERD stressing the potential high morbidity and severity of the underlying asthma and rhinosinusitis are discussed and proposed. Newly described sub-phenotypes and emerging sub-endotypes of N-ERD are potentially relevant for new and more specific (eg, biological) treatment modalities. Finally, the document defines major gaps in our knowledge on N-ERD and unmet needs, which should be addressed in the future.

Benefits and harms of aspirin desensitization for aspirin‐exacerbated respiratory disease: a systematic review and meta‐analysis

“…Practice guidelines increasingly recommend aspirin desensitization due to conclusion of clear benefit over harm . Single‐arm observational studies report adverse effects severe enough to cause aspirin discontinuation in 8% to 23%, but without a comparator group, information about safety is limited .…”

“…Aspirin desensitization is increasingly recommended and used to treat upper airway disease activity in AERD . Although the exact mechanism of aspirin desensitization in AERD remains unknown, it is thought to downregulate inflammatory leukotriene E 4 receptors and prostaglandin D 2 production .…”

“…This therapy initially involves administering increasing doses of oral aspirin over hours to days to a target dose of 325 to 650 mg. This is followed by lifelong daily aspirin treatment to maintain desensitization, typically 650 to 1300 mg per day, because desensitization is lost in as little as 48 hours off therapy . Recent guidelines and systematic review to date are mostly informed by observational studies concluding that aspirin desensitization's benefits strongly outweigh its harms.…”

EUFOREA consensus on biologics for CRSwNP with or without asthma

“…Using patient questionnaires to measure the prevalence of CRSwNP yielded estimates of 2.1% (France) to 4.3% (Finland) in Europe and 1.1% in China . CRSwNP comprises a heterogeneous group of patients who differ with respect to coexisting asthma, allergy, NSAID‐exacerbated respiratory disease (N‐ERD), smoking, age of onset, and disease severity . Asthma affects 30%‐70% of the CRSwNP patients .…”

Medical algorithms: Management of chronic rhinosinusitis

“…Surgery has also been shown to reduce blood eosinophils in patients with CRSwNP. And finally, in patients with NSAID‐exacerbated respiratory disease desensitization is an option …”