Rapid and sustained effect of dupilumab on clinical and mechanistic outcomes in aspirin-exacerbated respiratory disease.

BACKGROUND: Dupilumab, a mAb targeting IL-4Rα, improves upper and lower airway symptoms in patients with aspirin-exacerbated respiratory disease (AERD), but the mechanisms leading to clinical improvement are not fully elucidated. OBJECTIVE: Our aim was to identify the mechanistic basis of clinical improvement in patients with AERD treated with dupilumab. METHODS: A total of 22 patients with AERD were treated with dupilumab for 3 months for severe asthma and/or chronic rhinosinusitis with nasal polyps. Clinical outcomes were assessed at baseline and at 1 and 3 months after initiation of dupilumab. Nasal fluid, urine, blood, and inferior turbinate scrapings were collected at the 3 time points for determination of mediator levels, cellular assays, and RNA sequencing. RESULTS: Participants had rapid improvement in clinical measures, including sense of smell, sinonasal symptoms, and lung function after 1 month of treatment with dupilumab; the improvements were sustained after 3 months of dupilumab. Baseline severity of smell loss was correlated with lower nasal prostaglandin E2 levels. Dupilumab increased nasal prostaglandin E2 level and decreased levels of nasal albumin, nasal and urinary leukotriene E4, and serum and nasal IgE. Transcripts related to epithelial dysfunction and leukocyte activation and migration were downregulated in inferior turbinate tissue after treatment with dupilumab. There were no dupilumab-induced changes in nasal eosinophilia. CONCLUSION: Inhibition of IL-4Rα in AERD led to rapid improvement in respiratory symptoms and smell, with a concomitant improvement in epithelial barrier function, a decrease in inflammatory eicosanoid levels, and an increase in the anti-inflammatory eicosanoid prostaglandin E2 level. The therapeutic effects of dupilumab are likely due to decreased IL-4Rα signaling on respiratory tissue granulocytes, epithelial cells, and B cells.

Efficacy and safety of benralizumab in chronic rhinosinusitis with nasal polyps: A randomized, placebo-controlled trial.

BACKGROUND: Eosinophilic inflammation has been implicated in the pathogenesis, severity, and treatment responsiveness of chronic rhinosinusitis with nasal polyps (CRSwNP). OBJECTIVE: We sought to assess the efficacy and safety of benralizumab-mediated eosinophil depletion for treating CRSwNP. METHODS: The phase 3 OSTRO study enrolled patients with severe CRSwNP who were symptomatic despite treatment with intranasal corticosteroids and who had a history of systemic corticosteroid (SCS) use and/or surgery for nasal polyps (NP). Patients were randomized 1:1 to treatment with benralizumab 30 mg or placebo every 4 weeks for the first 3 doses and every 8 weeks thereafter. Coprimary end points were change from baseline to week 40 in NP score (NPS) and patient-reported mean nasal blockage score reported once every 2 weeks. RESULTS: The study population comprised 413 randomized patients (207 in the benralizumab group and 206 in the placebo group). Benralizumab significantly improved NPS and nasal blockage score compared to placebo at week 40 (P ≤ .005). Improvements in Sinonasal Outcome Test 22 score at week 40, time to first NP surgery and/or SCS use for NP, and time to first NP surgery were not statistically significant between treatment groups. Nominal significance was obtained for improvement in difficulty in sense of smell score at week 40 (P = .003). Subgroup analyses suggested influences of comorbid asthma, number of NP surgeries, sex, body mass index, and baseline blood eosinophil count on treatment effects. Benralizumab was safe and well tolerated. CONCLUSION: Benralizumab, when added to standard-of-care therapy, reduced NPS, decreased nasal blockage, and reduced difficulty with sense of smell compared to placebo in patients with CRSwNP. TRIAL REGISTRATION: ClinicalTrials.gov NCT03401229.

Inflammatory macrophage memory in nonsteroidal anti-inflammatory drug-exacerbated respiratory disease.

BACKGROUND: Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is a chronic inflammatory condition, which is driven by an aberrant arachidonic acid metabolism. Macrophages are major producers of arachidonic acid metabolites and subject to metabolic reprogramming, but they have been neglected in N-ERD. OBJECTIVE: This study sought to elucidate a potential metabolic and epigenetic macrophage reprogramming in N-ERD. METHODS: Transcriptional, metabolic, and lipid mediator profiles in macrophages from patients with N-ERD and healthy controls were assessed by RNA sequencing, Seahorse assays, and LC-MS/MS. Metabolites in nasal lining fluid, sputum, and plasma from patients with N-ERD (n = 15) and healthy individuals (n = 10) were quantified by targeted metabolomics analyses. Genome-wide methylomics were deployed to define epigenetic mechanisms of macrophage reprogramming in N-ERD. RESULTS: This study shows that N-ERD monocytes/macrophages exhibit an overall reduction in DNA methylation, aberrant metabolic profiles, and an increased expression of chemokines, indicative of a persistent proinflammatory activation. Differentially methylated regions in N-ERD macrophages included genes involved in chemokine signaling and acylcarnitine metabolism. Acylcarnitines were increased in macrophages, sputum, nasal lining fluid, and plasma of patients with N-ERD. On inflammatory challenge, N-ERD macrophages produced increased levels of acylcarnitines, proinflammatory arachidonic acid metabolites, cytokines, and chemokines as compared to healthy macrophages. CONCLUSIONS: Together, these findings decipher a proinflammatory metabolic and epigenetic reprogramming of macrophages in N-ERD.

Studies of the role of basophils in aspirin-exacerbated respiratory disease pathogenesis.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by the triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and intolerance to cyclooxygenase-1 enzyme inhibitors. The underlying mechanisms contributing to AERD pathogenesis are not fully understood, but AERD is characterized by an enhanced type 2 inflammatory phenotype. Basophils are potent type 2 effector cells, but their involvement in AERD pathophysiology remains unclear. OBJECTIVE: We sought to characterize the systemic and local basophil responses in patients with AERD compared with patients with CRSwNP. METHODS: Sinonasal tissues including inferior turbinate and/or nasal polyps (NPs) and peripheral blood were collected from controls, patients with AERD, and patients with CRSwNP. Expression of cell surface (CD45, FcεRI, CD203c), activation (CD63), and intracellular (2D7) markers associated with basophils was characterized using flow cytometry. Clinical data including Lund-Mackay scores and pulmonary function were obtained. RESULTS: The mean number of basophils (CD45+CD203c+FcεRI+CD117-) detected in AERD NPs (147 ± 28 cells/mg tissue) was significantly elevated compared with that detected in CRSwNP NPs (69 ± 20 cells/mg tissue; P = .01). The number of circulating basophils was significantly elevated in patients with AERD (P = .04). Basophils in NPs had significantly higher CD203c and CD63 mean fluorescence intensity compared with blood in both conditions (P < .01). Basophils from AERD NPs had lower expression of the granule content marker 2D7 compared with those from matched blood (P < .01) or NPs of patients with CRSwNP (P = .06), suggesting ongoing degranulation. Basophil 2D7 mean fluorescence intensity significantly correlated with pulmonary function (r = 0.62; P = .02) and inversely correlated with sinonasal inflammation (r = -0.56; P = .004). CONCLUSIONS: Increased basophil numbers and extent of ongoing degranulation in NPs of patients with AERD compared with patients with CRSwNP may contribute to the exaggerated disease pathogenesis and severity unique to AERD.

Clinical evaluation and diagnosis of aspirin-exacerbated respiratory disease.

Aspirin-exacerbated respiratory disease (AERD) is a condition composed of chronic rhinosinusitis with nasal polyposis and asthma that is defined by respiratory hypersensitivity reactions to the cyclooxygenase 1-inhibitory effects of nonsteroidal anti-inflammatory drugs. It is diagnosed in 5% to 15% of patients with asthma and is even more common in those with comorbid nasal polyposis. Diagnosis is confirmed after an aspirin challenge procedure, yet many patients present with all components and can reliably be diagnosed by history. Patients with AERD commonly experience severe uncontrolled nasal polyposis and require multispecialty evaluation to properly stage and treat this condition. The presence of nasal polyposis plays a large component in the diminished quality of life in patients with AERD. In the last decade, multiple new therapeutic areas have been approved for type 2 airway diseases, offering patients with AERD many more options for control. This makes an early and accurate diagnosis of AERD important in the care of the larger population of type 2 airway diseases.

IL-5Rα marks nasal polyp IgG4- and IgE-expressing cells in aspirin-exacerbated respiratory disease.

BACKGROUND: The cause of severe nasal polyposis in aspirin-exacerbated respiratory disease (AERD) is unknown. Elevated antibody levels have been associated with disease severity in nasal polyps, but upstream drivers of local antibody production in nasal polyps are undetermined. OBJECTIVE: We sought to identify upstream drivers and phenotypic properties of local antibody-expressing cells in nasal polyps from subjects with AERD. METHODS: Sinus tissue was obtained from subjects with AERD, chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), CRS without nasal polyps, and controls without CRS. Tissue antibody levels were quantified via ELISA and immunohistochemistry and were correlated with disease severity. Antibody-expressing cells were profiled with single-cell RNA sequencing, flow cytometry, and immunofluorescence, with IL-5Rα function determined through IL-5 stimulation and subsequent RNA sequencing and quantitative PCR. RESULTS: Tissue IgE and IgG4 levels were elevated in AERD compared with in controls (P < .01 for IgE and P < .001 for IgG4 vs CRSwNP). Subjects with AERD whose nasal polyps recurred rapidly had higher IgE levels than did subjects with AERD, with slower regrowth (P = .005). Single-cell RNA sequencing revealed increased IL5RA, IGHG4, and IGHE in antibody-expressing cells from patients with AERD compared with antibody-expressing cells from patients with CRSwNP. There were more IL-5Rα+ plasma cells in the polyp tissue from those with AERD than in polyp tissue from those with CRSwNP (P = .026). IL-5 stimulation of plasma cells in vitro induced changes in a distinct set of transcripts. CONCLUSIONS: Our study identifies an increase in antibody-expressing cells in AERD defined by transcript enrichment of IL5RA and IGHG4 or IGHE, with confirmed surface expression of IL-5Rα and functional IL-5 signaling. Tissue IgE and IgG4 levels are elevated in AERD, and higher IgE levels are associated with faster nasal polyp regrowth. Our findings suggest a role for IL-5Rα+ antibody-expressing cells in facilitating local antibody production and severe nasal polyps in AERD.

Nasal polyp epithelial atypia and exposure to nickel and copper.

BACKGROUND: Possible factors for cell atypia in nasal mucosa include noxious chemicals: ammonia, formaldehyde and heavy metals. AIMS: Case presentation of a nasal polyp with epithelial dysplasia in a worker exposed to nickel and copper salt dust. CASE REPORT: A 27-year-old man complained of impaired nasal breathing and mild right-sided epistaxis. He was exposed to copper and nickel salt dust for 6 years. Clinical examination showed a polypoid lesion arising from the right middle turbinate. Histopathological examination of the excised lesion showed high-grade epithelial dysplasia. Duration of exposure and concentration of heavy metals in serum suggest the biological plausibility of exposure to these factors and development of epithelial dysplasia in the nasal mucosa. CONCLUSIONS: Epithelial dysplasia may occasionally be noted in inflammatory nasal polyps, especially in workers exposed to heavy metals.

[Widal's triad : clinical manifestations, pathophysiology and therapeutic advances]. / Syndrome de Widal : manifestations cliniques, physiopathologie et avancées thérapeutiques.

NSAID-Exacerbated respiratory disease (also known as Samter's or Widal's triad, aspirin-exacerbated respiratory disease) is characte- rized by asthma, nasal polyposis and hypersensitivity to NSAIDs. The pathogenesis of this chronic inflammation arises from an imbalance in arachidonic acid metabolism, leading to an increase in pro- inflammatory cysteinyl-leukotrienes. The treatment is based on drug management of asthma and polyps and, in advanced situations, surgical management of polyposis. Monoclonal antibodies have shown promising results in the further medical treatment of this entity.

Le syndrome de Widal (SW) (également connu sous le nom de triade de Samter, maladie respiratoire exacerbée par l'Aspirine) est une entité clinique caractérisée par la triade comprenant un asthme, une polypose nasale et une intolérance aux AINS. La physiopathologie de cette maladie, bien qu'incomplètement élucidée, est caractérisée par un déséquilibre dans le métabolisme de l'acide arachidonique (AA) en faveur de la voie des cystéinyl- leucotriènes (cysLT). Son traitement repose sur une prise en charge médicamenteuse agressive de l'asthme et des polypes et, dans des situations avancées, la prise en charge chirurgicale de la polypose. L'avènement des traitements par anticorps monoclo- naux a montré des résultats encourageants pour les alternatives thérapeutiques futures.

Aspirin-exacerbated respiratory disease and current treatment modalities.

Aspirin-exacerbated respiratory disease (AERD) refers to the combination of asthma, chronic rhinosinusitis with nasal polyposis, and acute upper and lower respiratory tract reactions to the ingestion of aspirin (acetylsalicylic acid, ASA) and other cyclooxygenase-1 inhibiting non-steroidal anti-inflammatory drugs. AERD affects 0.3-0.9 % of the general population. AERD generally occurs due to abnormalities in mediators and expression of arachidonic acid biosynthesis. Local IgE responses to staphylococcal enterotoxins may also be responsible for eosinophilic activation in the nasal polyp tissues of AERD patients. Clinical features of AERD include the onset of nasal congestion with anosmia, progressing to chronic pansinusitis and nasal polyps that regrow rapidly after surgery. Aspirin desensitization, Leukotriene-modifying agents, biologic agents, management of asthma, chronic rhinosinusitis, and nasal polyposis are recommended as treatment modalities. Immunotherapy is prescribed only to those AERD patients who experience clear seasonal or perennial allergy symptoms in addition to the symptoms attributable to chronic nasal polyposis. There are also investigational and dietary therapies. In this review, the important aspects of AERD will be presented, along with a literature survey.

Olfaction and sinonasal symptoms in patients with CRSwNP and AERD and without AERD: a cross-sectional and longitudinal study.

Oral aspirin challenge (OAC) reveals aspirin-exacerbated respiratory disease (AERD) in approximately 50% of unselected patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). Smell loss is one factor that predicts the outcome of OAC. The present study aims to unveil differences in olfactory function between patients with CRSwNP with and without AERD by means of a validated reliable test for odor threshold, discrimination and identification. Additionally, Beck Depression Inventory (BDI) and Sinonasal Outcome Test 22 (SNOT 22) were applied. 31 patients were tested before and 7 months after OAC and aspirin desensitization in case of diagnosed AERD. AERD was diagnosed in 16 and excluded in 15 patients. Patients with AERD demonstrated significantly more olfactory loss, but no difference in BDI or SNOT 22 at baseline. Olfaction of the groups equalized at follow-up. Sinonasal complaints decreased significantly in patients with AERD, but not in the group without AERD. Olfactory loss is a valuable marker for AERD, but due to the variance of olfactory test results prediction of AERD by exclusively any of the applied olfactory tests appears unreliable.

[Hypersensitivity to acetylsalicylic acid]. / Nadwrazliwosc na kwas acetylosalicylowy.

Hypersensitivity to acetylsalicylic acid (ASA) is characterized by the co-occurrence of symptoms so-called aspirin triad, which include bronchial asthma, chronic rhinitis and sinusitis and the nasal mucosa polyps. The disease affects about 1% of the general population and in patients with bronchial asthma incidence may be as high as 10%. Hypersensitivity to aspirin is a difficult diagnostic problem, so the increased knowledge on this subject is a very important for the physicians of many specialties.

Cysteinyl leukotriene overproduction in aspirin-exacerbated respiratory disease is driven by platelet-adherent leukocytes.

Cysteinyl leukotriene (cysLT) overproduction is a hallmark of aspirin-exacerbated respiratory disease (AERD), but its mechanism is poorly understood. Because adherent platelets can convert the leukocyte-derived precursor leukotriene (LT)A(4) to LTC(4), the parent cysLT, through the terminal enzyme LTC(4) synthase, we investigated the contribution of platelet-dependent transcellular cysLT production in AERD. Nasal polyps from subjects with AERD contained many extravascular platelets that colocalized with leukocytes, and the percentages of circulating neutrophils, eosinophils, and monocytes with adherent platelets were markedly higher in the blood of subjects with AERD than in aspirin-tolerant controls. Platelet-adherent subsets of leukocytes had higher expression of several adhesion markers than did platelet nonadherent subsets. Adherent platelets contributed more than half of the total LTC(4) synthase activity of peripheral blood granulocytes, and they accounted for the higher level of LTC(4) generation by activated granulocytes from subjects with AERD compared with aspirin-tolerant controls. Urinary LTE(4) levels, a measure of systemic cysLT production, correlated strongly with percentages of circulating platelet-adherent granulocytes. Because platelet adherence to leukocytes allows for both firm adhesion to endothelial cells and augmented transcellular conversion of leukotrienes, a disturbance in platelet-leukocyte interactions may be partly responsible for the respiratory tissue inflammation and the overproduction of cysLTs that characterize AERD.

Efficacy of EDS-FLU for Chronic Rhinosinusitis: Two Randomized Controlled Trials (ReOpen1 and ReOpen2).

BACKGROUND: Chronic rhinosinusitis (CRS) is a prevalent inflammatory disease. No medications are Food and Drug Administration-approved for the most common form, CRS without nasal polyps (also called "chronic sinusitis"). Novel biomechanics of the exhalation delivery system deliver fluticasone (EDS-FLU; XHANCE) to sinonasal areas above the inferior turbinate, especially sinus drainage pathways not reached by standard-delivery nasal sprays. OBJECTIVE: Assess EDS-FLU efficacy for CRS (irrespective of nasal polyps). METHODS: Two randomized, EDS-placebo-controlled trials in adults with CRS irrespective of polyps (ReOpen1) or exclusively without polyps (ReOpen2) were conducted at 120 sites in 13 countries. Patients received EDS-FLU 1 or 2 sprays/nostril, or EDS-placebo, twice daily for 24 weeks. Coprimary measures were composite symptom score through week 4 and ethmoid/maxillary sinus percent opacification by computed tomography at week 24. RESULTS: ReOpen1 (N = 332) composite symptom score least-squares mean change for EDS-FLU 1 or 2 sprays/nostril versus EDS-placebo was -1.58 and -1.60 versus -0.62 (P < .001, P < .001); ReOpen2 (N = 223), -1.54 and -1.74 versus -0.81 (P = .011, P = .001). In ReOpen1, sinus opacification least-squares mean change for EDS-FLU 1 or 2 sprays/nostril versus EDS-placebo was -5.58 and -6.20 versus -1.60 (P = .045, P = .018), and in ReOpen2, -7.00 and -5.14 versus +1.19 (P < .001, P = .009). Acute disease exacerbations were reduced by 56% to 66% with EDS-FLU versus EDS-placebo (P = .001). There were significant, and similar magnitude, symptom reductions in patients using standard-delivery nasal steroid products just before entering the study (P < .001). Adverse events were similar to standard-delivery intranasal steroids. CONCLUSIONS: EDS-FLU is the first nonsurgical treatment demonstrated to reduce symptoms, intrasinus opacification, and exacerbations in replicate randomized clinical trials in CRS, regardless of polyp status.

Eicosanoid imbalance correlates in vitro with the pattern of clinical symptoms of Samter's triad.

BACKGROUND: Hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) is often associated with chronic rhinosinusitis (CRS), nasal polyps (CRSwNP) and asthma, together known as Samter's triad. The disease is characterised by eicosanoid imbalance. In our study, we determined clinical and laboratory parameters in respect of three groups of patients: 1) CRSwNP, 2) CRSwNP and asthma (CRSwNP-A), and 3) CRSwNP with asthma and NSAID-triggered hypersensitivity (CRSwNP-AA). Our main goal was to improve the characterisation of the stages of development in Samter's triad, pointing to the homogeneous or heterogeneous course of disease. METHODOLOGY: Forty-three patients (10 CRSwNP, 14 CRSwNP-A, 19 CRSwNP-AA) and 10 control subjects were included in the study. Nasal assessment using the CRS visual analogue score, endoscopy- and computer tomography scores, allergy tests, analysis of sinus surgeries, asthma severity and in vitro functional eicosanoid tests (FET) with peripheral blood leucocytes were performed. RESULTS: The scores reflecting CRS symptoms such as nasal congestion, nasal discharge and smell impairment differed between the patients groups reflecting the severity of disease (CRSwNP-AA > CRSwNP-A > CRSwNP). Eicosanoid imbalance correlated with nasal congestion, nasal discharge and loss of smell. CONCLUSION: The data presented support the hypothesis of the continuous development of NSAID-triggered hypersensitivity, culminating in Samter's triad.

Subendotyping of Dermatophagoides pteronyssinus-Induced Rhinitis and Its Impact on Respiratory Comorbidities.

BACKGROUND: The impact of delayed hypersensitivity to Dermatophagoides pteronyssinus (DP) on comorbidities of allergic rhinitis (AR) is unknown. OBJECTIVE: The primary end point was to test the hypothesis that DP-induced AR could be divided into 2 subendotypes on the basis of presence or absence of a delayed-type mite sensitization detected by the positive result of atopy patch test for DP (DP-APT). The second end point was to evaluate differences in the long-term risk of respiratory comorbidities and nasal airway response to mite exposure. METHODS: In a prospective observational study, we included 472 patients with DP-induced AR. A total of 343 patients had positive results of skin prick test/serum specific IgE and DP-APT and were assigned to a subendotype with both IgE- and T-cell-mediated mite sensitization (BMSS). The remaining 129 patients without delayed-type mite sensitization were included in the subendotype with only IgE-mediated mite sensitization. Nasal allergen provocation test with active anterior rhinomanometry, paranasal sinuses computed tomography scan, nasal endoscopy, and spirometry were performed. RESULTS: At baseline, BMSS showed a larger increase in nasal airway resistance, total nasal score, and visual analogue scale score to mite exposure. During a 15-year follow-up, 56 patients developed chronic rhinosinusitis with nasal polyps, with higher incidence in BMSS than in the subendotype with only IgE-mediated mite sensitization (50 patients, 14.6% vs 6 patients, 12.4%; P < .001). BMSS also showed a higher incidence of conjunctivitis (25.7% vs 12.4%; P < .01). The rate of adult-onset asthma did not differ between groups, but patients with BMSS showed a more frequent link to chronic rhinosinusitis with nasal polyps (6 of 29 patients, 20.7% vs 0 of 10 patients, 0%). DP-APT independently predicted chronic rhinosinusitis with nasal polyps and conjunctivitis. CONCLUSIONS: Two subendotypes with significantly different clinical outcome can be identified among patients with DP-induced AR according to the presence of delayed-type mite sensitization detected by positive DP-APT result.

Inheritance of NSAID-Exacerbated Respiratory Disease.

Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) has been considered an acquired condition. Positive first-degree family history has been reported in 1% of cases. The geographic and genetic isolation of the Finnish population offers exceptional opportunities for inheritance studies. In this questionnaire study, we explored the familial aggregation of N-ERD in 66 Finnish families of patients with N-ERD. The majority of patients (67%) had a positive family history of NSAID intolerance, asthma, nasal polyposis, or N-ERD. Furthermore, 55% had a positive first-degree family history of asthma, 21% nasal polyposis, 20% NSAID intolerance, and 11% N-ERD. The prevalence of asthma, nasal polyposis, NSAID intolerance, and N-ERD among first-degree relatives was 13%, 5%, 4%, and 2%, respectively. We present the pedigrees of the 44 affected families. According to our findings, Finnish patients with N-ERD seem to have a genetic susceptibility to it.

Aspirin-Exacerbated Respiratory Disease and the Unified Airway: A Contemporary Review.

Aspirin-exacerbated respiratory disease (AERD) is characterized by abnormal arachidonic acid metabolism leading to chronic rhinosinusitis with nasal polyposis (CRSwNP), asthma, and upper and/or lower respiratory symptoms after ingestion of cyclooxygenase-1 inhibiting nonsteroidal antiinflammatory drugs. Diagnosis is clinical and may involve an aspirin challenge. Inflammatory biomarkers may be useful for diagnosis and treatment monitoring. Conventional medical management for asthma and CRSwNP is often inadequate. Endoscopic sinus surgery followed by continued medical management with or without aspirin desensitization frequently improves symptoms and objective disease measures. Biological agents targeting eosinophilic inflammation are promising alternatives to conventional management.

Therapeutic applications of capsaicin in humans to target conditions of the respiratory system: A scoping review.

BACKGROUND: Various studies have explored potential therapeutic applications of capsaicin in human medicine, for example in pain, obesity, cancer, cardiovascular and respiratory disease. The aim of this scoping review was to identify and chart available evidence on therapeutic applications of capsaicin in humans using any mode of capsaicin delivery to treat conditions of the respiratory system. METHODS: Electronic bibliographic databases (Web of Science, PubMed, Medline, ScienceDirect, Embase, Scopus) were searched from inception to 2021 to identify experimental studies reporting clinical outcomes of therapeutic applications of capsaicin. Studies with or without control group published in peer-reviewed journals were included. Animal studies, studies of human cell lines, and physiological proof of concept studies were excluded. Reviewer pairs independently double-screened 2799 search results for inclusion. RESULTS: Twenty-three original studies were included. Capsaicin has been investigated for the treatment of non-allergic rhinitis (n = 15), nasal polyposis (n = 3), allergic rhinitis (n = 2), unexplained chronic cough (n = 2), and prevention of aspiration pneumonia (n = 1). Modes of delivery included intranasal application (nasal spray, soaked pads, solution), inhalation, ingestion, and aural ointment. Seventeen studies reported positive effects of capsaicin on clinical outcomes for rhinitis, nasal polyposis, chronic cough, and pneumonia. Sixteen studies reported on the safety of capsaicin, with no reports of significant adverse events and overall fair to good patient acceptability. CONCLUSION: While the evidence identified in this review has limited implications for clinical practice, studies support the general safety of capsaicin as administered in these studies and highlight emerging strands of research and clinical hypotheses which warrant further examination.