Randomized, placebo controlled, double blinded pilot superiority phase 2 trial to evaluate the effect of curcumin in moderate to severe asthmatics.

BACKGROUND: Curcumin, a derivative of the spice turmeric, has been adopted by Eastern medicine for centuries as an adjunct to treat several medical conditions (e.g., anorexia and arthritis) because of its well-established anti-inflammatory properties. Studies have shown that the use of curcumin in mice models has led to reduction in several inflammatory markers as well as key inflammatory pathway enzymes. As a result, studies in Western medicine have developed to determine if this recognized benefit can be utilized for patients with inflammatory lung diseases, such as asthma. This study will seek to better understand if curcumin can be used as an adjunctive therapy for improving asthma control of patients with moderate to severe asthma; a finding we hope will allow for a more affordable treatment. METHODS: This study will utilize a randomized, placebo controlled, double blinded pilot superiority phase 2 trial at an outpatient pulmonary clinic in Southern California, USA. Subjects will be receiving Curcumin 1500 mg or matching placebo by mouth twice daily for the study period of 12 weeks. Subjects will be randomized to either a placebo or intervention Curcumin. Subjects will have 6 clinic visits: screening visit, a baseline visit, monthly clinic visits (weeks 4, 8, and 12), at weeks 4, 8, and a follow-up clinic visit or phone-call (week 16). Changes in asthma control test scores, number of days missed from school/work, FEV1 (% predicted), FEV1/FVC ratio, FVC (% predicted), blood eosinophil count, blood total IgE, and FeNO levels will be compared by group over time. DISCUSSION: The therapeutic effects of curcumin have been studied on a limited basis in asthmatics and has shown mixed results thus far. Our study hopes to further establish the benefits of curcumin, however, there are potential issues that may arise from our study design that we will address within this paper. Moreover, the onset of the COVID-19 pandemic has resulted in safety concerns that have delayed initiation of our study. This study will contribute to existing literature on curcumin's role in reducing lung inflammation as it presents in asthmatics as well as patients suffering from COVID-19. TRIAL REGISTRATION: This study protocol has been approved by the Institutional Review Board at Loma Linda University Health, (NCT04353310). IND# 145101 Registered April 20th, 2020. https://clinicaltrials.gov/ct2/show/NCT04353310 .

A rare case report of polyangiitis overlap syndrome: granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is a systemic ANCA-associated vasculitis characterized by necrotizing granulomatous inflammation and a predilection for the upper and lower respiratory tract. Eosinophilic granulomatosis with polyangiitis (EGPA) is also a systemic ANCA-associated vasculitis, but EGPA is characterized by eosinophilic as well as granulomatous inflammation and is more commonly associated with asthma and eosinophilia. Polyangiitis overlap syndrome is defined as systemic vasculitis that does not fit precisely into a single category of classical vasculitis classification and/or overlaps with more than one category. Several polyangiitis overlap syndromes have been identified, however, there are very few case reports of an overlap syndrome involving both GPA and EGPA in the medical literature. CASE PRESENTATION: We conducted a PUBMED literature review using key words 'granulomatosis with polyangiitis,' 'Wegener's,' 'GPA,' 'eosinophilic granulomatosis with polyangiitis,' 'Churg-Strauss,' 'EGPA,' 'overlap syndrome,' 'Wegener's with eosinophilia,' and 'GPA with eosinophilia' in English only journals from 1986 to 2017. Relevant case reports and review articles of overlap syndromes of GPA and EGPA were identified. We aim to report a unique case of GPA and EGPA overlap syndrome and review the cases that have been previously described. Between 1986 and 2017, we identified 15 cases that represent an overlap syndrome with compelling features of both GPA and EGPA. Patients ranged in age between 21 and 78. Of those whose gender was identified, 80 % of the patients were female. All cases described involved the lungs, 60 % reported sinus involvement, and more than 50 % displayed renal involvement. An overwhelming majority of patients were positive for c-ANCA and demonstrated eosinophilia (peripheral blood or tissue eosinophilia). A preponderance of the cases described were treated with systemic corticosteroids combined with an immunosuppressive/cytotoxic agents. CONCLUSION: To our knowledge, there have been very few cases reported of an overlap syndrome of GPA and EGPA. Identification of patients with a polyangiitis overlap syndrome of GPA and EGPA is imperative as prognosis, longitudinal management and treatment modalities may differ between these entities.

Utility of multimodal sampling and testing during advanced bronchoscopy for diagnosing atypical respiratory infections in a Coccidioides-endemic region.

Background: The role of advanced diagnostic bronchoscopy (ADB) for assessing atypical respiratory infections is unclear. The purpose of this study was to ascertain: (I) the diagnostic utility of ADB-tissue sampling in patients with focal thoracic lesions due to atypical respiratory infections; (II) how multimodal bronchoscopic sampling and testing enhance diagnosis in a Coccidioides-endemic region. Methods: A retrospective observational cohort study analyzing all ADBs performed over a 10-year period in patients with focal thoracic lesions diagnosed with a non-malignant disorder. Only cases which procured lower respiratory tract secretion and tissue samples by ADB, and had both cytohistology and culture results available were included. Results: Among 403 subjects with non-malignant disease, 136 (33.7%) were diagnosed with atypical respiratory infections, with ADB contributing a diagnosis in 119 (87.5%) of these. Coccidioidal disease was independently associated with a cytohistologic diagnosis [odds ratio =7.64, 95% confidence interval (CI): 2.51-23.26; P<0.001]. Mycobacteria were more effectively identified by culture (overall yield of 8.4%, vs. 2.7% by cytohistology; P<0.001). Among subjects for which both respiratory secretion and tissue sampling were dual-tested with culture and cytology/cytohistology, adding ADB-guided transbronchial needle aspiration and/or forceps biopsy (TBNA/TBFB) to bronchoalveolar lavage and/or bronchial washings (BAL/BW) more than doubled the yield for dimorphic fungi, from 7.1% to 15.1% (increase of 8.0%, 95% CI: 5.2-11.9%). For lung lesions, adding tissue culture to dual TBNA/TBFB cytohistology-tested lung samples doubled the proportion diagnosed with atypical infection over using TBNA-cytohistology alone (increase of 15.8%, 95% CI: 10.4-23.1%). Adding lymph node to lung sampling increased the proportion diagnosed with coccidioidomycosis by 8.8% (95% CI: 4.8-15%). Among subjects with atypical respiratory infections, major ADB-related complications occurred in 1.5%. Conclusions: ADB is useful for diagnosing atypical respiratory infections manifesting as focal thoracic lesions. A multimodal approach to both sampling and testing enhances yield, while maintaining a favorable procedure safety profile. Cytohistology testing and nodal sampling are beneficial for pulmonary coccidioidomycosis, and culture for mycobacterial disease. The approach to ADB-sampling should be adjusted according to clinical context and regional infection patterns.

Effectiveness of Angiotensin II for Catecholamine Refractory Septic or Distributive Shock on Mortality: A Propensity Score Weighted Analysis of Real-World Experience in the Medical ICU.

Angiotensin II (ATII) was approved for septic or other distributive shock due to its property of increasing blood pressure within 3 hours. Limited data exist regarding its effectiveness when used in real-world clinical practice. OBJECTIVES: This study examined ATII as a third-line vasopressor based on institutional approval. DESIGN: Retrospective observational cohort study. SETTING AND PARTICIPANTS: Medical ICU at an academic tertiary care medical center. Adult patients requiring 3 or more vasopressor agents for septic shock or other forms of distributed shock from September 1, 2018, to January 31, 2020. MAIN OUTCOMES AND MEASURES: Effect of ATII after norepinephrine and vasopressin on mortality and mean arterial blood pressure response after 3 hours of administration. RESULTS: One-hundred forty-seven patients, 56 receiving ATII and 91 receiving another vasopressor (non-ATII), were enrolled. Patients in the ATII group had higher mortality compared to the non-ATII group, and more required 5 or greater vasopressor agents (p < 0.01). After propensity score weighting, there remains a trend in higher mortality in the ATII compared to non-ATII group, but not statistically significant (86.0% vs 71.0%, p = 0.16). More patients in the ATII group continued to require 5 or greater vasopressor agents compared to the non-ATII group after propensity score weighting (45.9% vs 12.5%, p < 0.01). SOFA score was the only variable associated with mortality (OR = 1.25, 95% CI, 1.05-1.49; p = 0.01). Patients were considered a "responder" if mean arterial pressure greater than 65 mm Hg at 3 hours after the third vasopressor was initiated. Among the ATII group, 37.5% patients were responders compared to 45.1% responders in the non-ATII group (relative risk = 1.07, 95% CI, 0.6-1.93; p = 0.81). CONCLUSIONS AND RELEVANCE: Although previous data support the use of ATII due to its favorable hemodynamic response in patients with distributive shock, there was no observed benefit in mortality or hemodynamic response with ATII as a third-line vasopressor in our study of real-world patients.

SLE and Serum Complement: Causative, Concomitant or Coincidental?

BACKGROUND: Systemic Lupus Erythematosus (SLE) is an incurable autoimmune disorder with complement activation playing a key role in the pathogenesis of immune-mediated tissue injury. While quantifying complement to monitor SLE disease activity has been the standard of care since the 1950s, decreased complement levels are not consistently associated with flares. OBJECTIVE: We seek to clarify the SLE phenotype in which complement deficiency is causative, concomitant, or coincidental. METHODS: A PUBMED literature review was conducted using key words 'complement,' 'SLE,' and 'SLE flares' in English-only journals from 1972-2017. Relevant clinical studies and review articles were found that examined the measurement of complement levels in SLE, and more specifically, interpretation of low serum complement levels regardless of disease activity. CONCLUSION: Complement activation plays a key role in the pathophysiology of SLE and it is recommended to continue monitoring serum levels of C3 and C4 to assess for disease activity. However, it is important to note that decreased serum complement is not consistently associated with disease flares.It is clinically important to find novel ways to assess disease activity in SLE. Reduced serum levels of cell-bound complement activation products may more accurately reflect disease activity than conventional serum C3 and C4 monitoring.