Long-Term Efficacy and Safety Among Patients With Severe Eosinophilic Asthma Treated With Mepolizumab and Its Effect on Small Airways.

BACKGROUND: The major problem at the Cleveland Allergy and Asthma Center was the need for additional therapy for severe eosinophilic asthma patients who were steroid-dependent or required frequent bursts of prednisone. OBJECTIVES: The objectives of this study were to determine the efficacy of monthly mepolizumab (MP) injections up to 6½ years using Asthma Control Quesitonnaire-7 (ACQ-7), forced expiratory volume in 1 second (FEV1), forced expiratory flow at 25% to 75% (FEF25%-75%) overall and among super-responders, and to understand whether FEF25%-75% is an effective parameter to evaluate MP efficacy. METHODS: We reviewed the charts of 67 patients with severe eosinophilic asthma and compared the results between 47 super-responders and the rest of the cohort regarding ACQ-6, ACQ-7, eosinophils, FEV1, and FEF25%-75%. The groups of super-responders and all other patients were described with respect to initial and current values of the study end points using medians and 25th and 75th percentiles. Changes from the initial to the current values in the study end points were measured using percent changes. The Wilcoxon signed rank test was used within each group to test the null hypothesis of 0 median percent change. RESULTS: After 6½ years, there were no significant changes in FEV1. The FEF25%-75%, had a significant median percent increase of 40% among the super-responders (P < .001), which was substantially higher (P = .026) than the median percent increase of 13.8% observed among all other patients. CONCLUSIONS: The use of MP up to 6½ years was safe and effective, with significant changes to ACQ-7 and FEF25%-75% associated with MP treatment, but not the FEV1. A higher magnitude of changes was observed among super-responders than the rest of the cohort. Changes in FEF25%-75% were more meaningful than changes in FEV1 in evaluating pulmonary function responsiveness of severe eosinophilic asthma to MP.

Francis S. Morrison MD-Tribute to an apheresis leader.

Francis S. Morrison MD was among the early developers and promoters of the American Society for Apheresis (ASFA). His work was pivotal in creating a lasting institutional structure from which American apheresis medical practice would develop decades after his death. Francis Morrison is honored each year at the ASFA annual meeting as ASFA awards the Francis S. Morrison MD Memorial Award Lecture to an individual who stands out as among its most accomplished members. This tribute seeks to describe the person and the key accomplishments of Francis S. Morrison in the historical context of a time when the future of apheresis medicine was uncertain.

Antibodies against biotin-labeled red blood cells can shorten posttransfusion survival.

BACKGROUND: In hematologic and transfusion medicine research, measurement of red blood cell (RBC) in vivo kinetics must be safe and accurate. Recent reports indicate use of biotin-labeled RBC (BioRBC) to determine red cell survival (RCS) offers substantial advantages over 51 Cr and other labeling methods. Occasional induction of BioRBC antibodies has been reported. STUDY DESIGN AND METHODS: To investigate the causes and consequences of BioRBC immunization, we reexposed three previously immunized adults to BioRBC and evaluated the safety, antibody emergence, and RCS of BioRBC. RESULTS: BioRBC re-exposure caused an anamnestic increase of plasma BioRBC antibodies at 5-7 days; all were subclass IgG1 and neutralized by biotinylated albumin, thus indicating structural specificity for the biotin epitope. Concurrently, specific antibody binding to BioRBC was observed in each subject. As biotin label density increased, the proportion of BioRBC that bound increased antibody also increased; the latter was associated with proportional accelerated removal of BioRBC labeled at density 6 µg/mL. In contrast, only one of three subjects exhibited accelerated removal of BioRBC density 2 µg/mL. No adverse clinical or laboratory events were observed. Among three control subjects who did not develop BioRBC antibodies following initial BioRBC exposure, re-exposure induced neither antibody emergence nor accelerated BioRBC removal. DISCUSSION: We conclude re-exposure of immunized subjects to BioRBC can induce anamnestic antibody response that can cause an underestimation of RCS. To minimize chances of antibody induction and underestimation of RCS, we recommend an initial BioRBC exposure volume of ≤10 mL and label densities of ≤18 µg/mL.

Eosinophilia Is Associated with Improved COVID-19 Outcomes in Inhaled Corticosteroid-Treated Patients.

BACKGROUND: In addition to their proinflammatory effect, eosinophils have antiviral properties. Similarly, inhaled corticosteroids (ICS) were found to suppress coronavirus replication in vitro and were associated with improved outcomes in coronavirus disease 2019 (COVID-19). However, the interplay between the two and its effect on COVID-19 needs further evaluation. OBJECTIVE: To determine the associations among preexisting blood absolute eosinophil counts, ICS, and COVID-19-related outcomes. METHODS: We analyzed data from the Cleveland Clinic COVID-19 Research Registry (April 1, 2020 to March 31, 2021). Of the 82,096 individuals who tested positive, 46,397 had blood differential cell counts obtained before severe acute respiratory syndrome coronavirus 2 testing dates. Our end points included the need for hospitalization, admission to the intensive care unit (ICU), and in-hospital mortality. The effect of eosinophilia on outcomes was estimated after propensity weighting and adjustment. RESULTS: Of the 46,397 patients included in the final analyses, 19,506 had preexisting eosinophilia (>0.15 × 103 cells/µL), 5,011 received ICS, 9,096 (19.6%) were hospitalized, 2,129 required ICU admission (4.6%) and 1,402 died during index hospitalization (3.0%). Adjusted analysis associated eosinophilia with lower odds for hospitalization (odds ratio [OR] [95% confidence interval (CI)]: 0.86 [0.79-0.93]), ICU admission (OR [95% CI]: 0.79 [0.69-0.90]), and mortality (OR [95% CI]: 0.80 [0.68-0.95]) among ICS-treated patients but not untreated ones. The correlation between absolute eosinophil count and the estimated probability of hospitalization, ICU admission, and death was nonlinear (U-shaped) among patients not treated with ICS, and negative in treated patients. CONCLUSIONS: The association between eosinophilia and improved COVID-19 outcomes depends on ICS. Future randomized controlled trials are needed to determine the role of ICS and its interaction with eosinophilia in COVID-19 therapy.

Intranasal Corticosteroids Are Associated with Better Outcomes in Coronavirus Disease 2019.

BACKGROUND: Sites of entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are highly expressed in nasal epithelial cells; however, little is known about the impact of intranasal corticosteroids (INCS) on coronavirus disease 2019 (COVID-19)-related outcomes. OBJECTIVE: To determine the association between baseline INCS use and COVID-19-related outcomes. METHODS: Using the Cleveland Clinic COVID-19 Research Registry, we performed a propensity score matching for treatment with INCS before SARS-CoV-2 infection (April 1, 2020, to March 31, 2021). Of the 82,096 individuals who tested positive, 72,147 met inclusion criteria. Our endpoints included the need for hospitalization, admission to the intensive care unit (ICU), or in-hospital mortality. RESULTS: Of the 12,608 (17.5%) who were hospitalized, 2935 (4.1%) required ICU admission and 1880 (2.6%) died during hospitalization. A significant proportion (n = 10,187; 14.1%) were using INCS before SARS-CoV-2 infection. Compared with nonusers, INCS users demonstrated lower risk for hospitalization (adjusted odds ratio [OR] [95% confidence interval (CI)]: 0.78 [0.72; 0.85]), ICU admission (adjusted OR [95% CI]: 0.77 [0.65; 0.92]), and in-hospital mortality (adjusted OR [95% CI]: 0.76 [0.61; 0.94]). These findings were replicated in sensitivity analyses where patients on inhaled corticosteroids and those with allergic rhinitis were excluded. The beneficial effect of INCS was significant after adjustment for baseline blood eosinophil count (measured before SARS-CoV-2 testing) in a subset of 30,289 individuals. CONCLUSION: INCS therapy is associated with a lower risk for COVID-19-related hospitalization, ICU admission, or death. Future randomized control trials are needed to determine if INCS reduces the risk for severe outcomes related to COVID-19.

The epidemiology of platelet transfusions: an analysis of platelet use at 12 US hospitals.

BACKGROUND: Using the Recipient and Donor Epidemiology Study-III (REDS-III) recipient and donor databases, we performed a retrospective analysis of platelet use in 12 US hospitals that were participants in REDS-III. STUDY DESIGN AND METHODS: Data were electronically extracted from participating transfusion service and blood center computer systems and from medical records of the 12 REDS-III hospitals. All platelet transfusions from 2013 to 2016 given to patients aged 18 years and older were included in the analysis. RESULTS: There were 28,843 inpatients and 2987 outpatients who were transfused with 163,719 platelet products (103,371 apheresis, 60,348 whole blood derived); 93.5% of platelets were leukoreduced and 72.5% were irradiated. Forty-six percent were transfused to patients with an International Classification of Diseases, 9th/10th Revision (ICD-9/10) diagnosis of leukemia, myelodysplastic syndrome (MDS), or lymphoma. The general ward and the intensive care unit (ICU) were the most common issue locations. Only 54% of platelet transfusions were ABO identical; and 60.6% of platelet transfusions given to Rh-negative patients were Rh positive. The most common pretransfusion platelet count range for inpatients was 20,000 to 50,000/µL, for outpatients it was 10,000 to 20,000/µL. Among ICU patients, 35% of platelet transfusion episodes had a platelet count of greater than 50,000/µL; this was only 8% for general ward and 2% for outpatients. The median posttransfusion increment, not corrected for platelet dose and/or patient size, ranged from 12,000 to 20,000/µL for inpatients, and from 17,000 to 27,000/µL for outpatients. CONCLUSIONS: These data from one of the largest reviews of platelet transfusion practice to date provide guidance for where to focus future clinical research studies and platelet blood management programs.

Special education use in elementary school by children with nonsyndromic orofacial clefts.

BACKGROUND: Children with nonsyndromic orofacial clefts (NS OFCs) may require exceptional children's (EC) services for academic delays. We examined EC service use of children with and without NS OFCs in NC in elementary school. METHODS: We included 559 children with NS OFCs and 6,822 children without birth defects who had NC educational records. We estimated prevalence ratios, trends in enrollment, and characteristics of eligibility classification using descriptive statistics and logistic regression by cleft subtype and race/ethnicity. We estimated the odds of third grade retention by EC enrollment using logistic regression with inverse probability of treatment weights. RESULTS: Children with NS OFCs were 3.02 (95% CI: 2.50, 3.64) times as likely to receive third grade special education (SE) services compared to unaffected peers. The prevalence odds was highest among children with CL+P (OR: 4.61, 95% CI: 3.49, 6.09) declining by 54% by fifth grade. The prevalence odds of SE for white children was approximately 1.50 times that for African American children in fourth and fifth grades. Approximately 33% of children with NS OFCs within each racial/ethnic group received SE in third grade. African American children were twice as likely to receive services under specific learning disability. Children with NS OFCs receiving EC services were 44% (OR: 0.56; 95% CI: 0.13, 2.38) less likely to be retained in third grade compared to children with NS OFCs who were not receiving services. CONCLUSIONS: Children with NS OFCs are more likely to receive SE services in elementary school compared to their unaffected peers. The eligibility category differed by racial/ethnic group.

Development, validation, and potential applications of biotinylated red blood cells for posttransfusion kinetics and other physiological studies: evidenced-based analysis and recommendations.

The current reference method in the United States for measuring in vivo population red blood cell (RBC) kinetics utilizes chromium-51 (51 Cr) RBC labeling for determining RBC volume, 24-hour posttransfusion RBC recovery, and long-term RBC survival. Here we provide evidence supporting adoption of a method for kinetics that uses the biotin-labeled RBCs (BioRBCs) as a superior, versatile method for both regulatory and investigational purposes. RBC kinetic analysis using BioRBCs has important methodologic, analytical, and safety advantages over 51 Cr-labeled RBCs. We critically review recent advances in labeling human RBCs at multiple and progressively lower biotin label densities for concurrent, accurate, and sensitive determination of both autologous and allogeneic RBC population kinetics. BioRBC methods valid for RBC kinetic studies, including successful variations used by the authors, are presented along with pharmacokinetic modeling approaches for the accurate determination of RBC pharmacokinetic variables in health and disease. The advantages and limitations of the BioRBC method-including its capability of determining multiple BioRBC densities simultaneously in the same individual throughout the entire RBC life span-are presented and compared with the 51 Cr method. Finally, potential applications and limitations of kinetic BioRBC determinations are discussed.

Red blood cell alloimmunization in sickle cell disease: assessment of transfusion protocols during two time periods.

BACKGROUND: Prevention of red blood cell (RBC) alloimmunization in patients with sickle cell disease (SCD) focuses on phenotypic RBC matching. We assessed alloimmunization among transfused patients with SCD after implementing leukoreduction and prophylactic antigen matching (PAM). STUDY DESIGN AND METHODS: Retrospective review of transfusion and medical records for SCD patients 18 months to 81 years of age was performed covering two 5-year periods: Period 1, no PAM, occasional leukoreduction, and Period 2, consistent leukoreduction and extended PAM (Rh, Kell, S, Fy, Jk) for patients already alloimmunized. Patients transfused in Period 1 were excluded from Period 2. RESULTS: A total of 293 patients were transfused in Period 1 and 183 in Period 2. Median time between first sample and last type and screen after transfusion was 2.12 years in Period 1 and 1.03 years in Period 2. Initial alloimmunization prevalence was lower in Period 2 (26.2%) versus Period 1 (37.5%) and after subsequent transfusions in Period 2 (23.8%) versus Period 1 (45.7%), although without significant difference after adjusting for number of units transfused, percentage of leukoreduced RBCs, sex, and age. Alloimmunized patients received more nonleukoreduced RBCs in Period 1 than nonalloimmunized. Patients transfused during inflammatory conditions were not significantly more likely to become alloimmunized. CONCLUSIONS: The prevalence of initial and subsequent RBC alloimmunization in Period 2 was lower than that in Period 1; however, overall prevalence remained high. We recommend leukoreduced, hemoglobin S-negative Rh and Kell PAM RBCs for transfusion of patients with SCD. Component and recipient factors affecting alloimmunization should be studied further.