Absolute Eosinophil Count Research Articles

The impact of CFTR modulator triple therapy on type 2 inflammatory response in patients with cystic fibrosis

BackgroundTreatment of cystic fibrosis (CF) has been revolutionized by the use of cystic fibrosis transmembrane conductance regulator (CFTR) protein modulators such as elexacaftor/tezacaftor/ivacaftor (ETI) triple therapy. Prior studies support a role for type 2 (T2) inflammation in many people with CF (PwCF) and CF-asthma overlap syndrome (CFAOS) is considered a separate clinical entity. It is unknown whether initiation of ETI therapy impacts T2 inflammation in PwCF. We hypothesized that ETI initiation decreases T2 inflammation in PwCF.MethodsA single center retrospective chart review was conducted for adult PwCF. As markers of T2 inflammation, absolute eosinophil count (AEC) and total immunoglobulin E (IgE) data were collected longitudinally 12 months prior to ETI therapy initiation and 12 months following therapy initiation. Multivariable analyses adjusted for the age, gender, CFTR mutation, disease severity, inhaled steroid use, and microbiological colonization.ResultsThere was a statistically significant reduction (20.10%, p < 0.001) in 12-month mean total IgE following ETI initiation; this change remained statistically significant in the multivariate model. The longitudinal analysis demonstrated no change in AEC following therapy initiation.ConclusionThis study demonstrates that there is a statistically significant percent reduction in mean total IgE but no change in AEC following ETI initiation. ETI may lead to decreased antigen and superantigen load in the airway as a result of improved mucociliary clearance and these changes may drive the decline in total IgE, without influencing the epigenetic drivers of eosinophilic inflammation. Further studies are warranted to determine the underlying mechanism of ETI impact on T2 inflammation and possible role for asthma immunomodulator therapy post ETI initiation in CFAOS.

Hypereosinophilic Syndrome with Endomyocarditis: Identification by Next-Generation Sequencing of the JAK2-V617F Mutation.

Hypereosinophilic syndrome requires a peripheral absolute eosinophil count of ≥1.5 × 109 /L with clinical manifestations attributable to peripheral or tissue hypereosinophilia. Clinical manifestations can vary greatly, with the majority of patients relatively asymptomatic and the eosinophilia detected incidentally. However, in a minority of hypereosinophilia cases, they may present with severe lifethreatening organ dysfunction affecting skin, lung, heart, gastrointestinal tract, and nervous system. A case of hypereosinophilia with potentially life-threatening cardiovascular involvement is discussed. Initial laboratory investigations showed an elevated white blood cell count with 60% eosinophils. An endomyocardial biopsy revealed eosinophilic endomyocarditis with granuloma, rare giant cells, and no vasculitis, microorganisms, or malignancy. Her presentation met the criteria for either hypereosinophilic syndrome or eosinophilic granulomatosis with polyangitis. Molecular genetic analysis was negative for myelodysplastic syndrome panel/ Platelet Derived Growth Factor Receptor Beta (PDGFRB) (5q32)/Fibroblast Growth Factor Receptor 1 (FGFR1) Fluorescence In Situ Hybridization (FISH), Feline McDonough Sarcoma-related Tyrosine Kinase 3 (FLT3) Internal Tandem Duplication (ITD) mutation, Calregulin (CALR) exon 9 mutation, and T-cell gene rearrangement/polymerase chain reaction. Bone marrow biopsy revealed a mildly hypocellular marrow with multilineage hematopoiesis,+ megakaryocyte dysplasia, and focal eosinophilia. No excess blasts, no monotypic B-cell population, and no discrete pan T-cell aberrancies were found. Bone marrow cytogenetic studies showed a normal signal pattern for myeloproliferative neoplasms panel/Sec1 Family Domain Containing 2 (SCFD2)-Ligand of Numb Protein-X (LNX)-Platelet-derived Growth Factor Receptor Alpha (PDGFRA) fluorescence in situ hybridization with a normal karyotype of 46 XX. Next-generation sequencing, however, was positive for the JAK2-V617F mutation, a rare molecular abnormality in hypereosinophilic syndrome. The prevalence ranges from approximately 0% to 4%. The JAK2 point mutation leads to aberrant tyrosine phosphorylation and increased cytokine activation. The case demonstrates the complexity and challenging nature of advanced diagnostic opportunities in hypereosinophilia and the potential use, in select subsets, of targeted treatments such as tyrosine kinase inhibitors.

Absolute eosinophil count is a reliable prognostic marker in patients with liver cirrhosis: a cross-sectional study at rural central India

BackgroundVarious laboratory parameters like C-reactive protein (CRP), Cortisol, and Von Willebrand factor antigen have been evaluated independently in foreseeing outcomes of cirrhotic patients. As these parameters lack cost-effectiveness in a rural setup, there is a need for a cost effective and feasible prognostic marker for cirrhotic patients. The present study was aimed at evaluating the role of Absolute Eosinophil Count (AEC) as a prognostic marker in cirrhotic patients.MethodsThis cross-sectional study was conducted at a rural tertiary care teaching hospital in central India from August 2019 to September 2021. AEC was measured from counter report as a part of automated complete blood counts. Child-Turcotte-Pugh (CTP) score and Model for end stage liver disease (MELD) score were calculated at the time of admission. AEC levels on admission were correlated with mortality and with CTP score and MELD score.ResultsA total of 110 patients were enrolled with mean age of 46.37 ± 11.6 years. AEC was the significant predictor of mortality at cut off point of ≤ 120 with 80.30% (AUC 0.803; 95% CI: 0.716 to 0.873). AEC was the significant predictor of CTP score ≥ 11 at cut off point of ≤ 148 (AUC 0.726; 95% CI: 0.633 to 0.807). AEC was the significant predictor of MELD score ≥ 25 at cut off point of ≤ 136 (AUC 0.74; 95% CI: 0.647 to 0.819). Significant negative correlation was seen between AEC with Child–Pugh score and MELD score with correlation coefficient of -0.257 and -0.258.ConclusionLow level of AEC on admission fairly predicted raised CTP score and MELD score on admission. Low AEC levels predicted increased mortality in cirrhotic patients making it a cheap and reliable prognostic marker in a rural setup.

Evaluation of the Clinicoradiological Profile in Cases of Allergic Bronchopulmonary Aspergillosis: An Original Research.

A complicated hypersensitive reaction to inhaled fungal antigens results in allergic bronchopulmonary aspergillosis (ABPA), an immunologic pulmonary disease. ABPA complicates nearly 2% of instances of persistent asthma as well as nearly 10% of chronic cases of steroid-dependent asthma, and it occurs most frequently in immunocompetent patients. The purpose of the current research was to analyze the radiological and clinical features of the participants as well as the serological association of ABPA. From April 2020 to April 2021, a retrospective investigation was conducted. The study included patients based on the International Society for Human and Animal Mycology's criteria for ABPA confirmation. Analysis was done on the demographic information and pathological and radiological test results of the patients. The patients' pre-bronchodilator and post-bronchodilator spirometry was compared, and asthmatic control was estimated. A total of 50 patients were investigated at in this study. Demographic findings indicated young subjects and aa female predominance. Cough was the most prevalent symptom in 84% of patients. Asthma of the bronchi was a risk factor for all of the patients. The mean serum immunoglobulin E level and the mean absolute eosinophil count were 533 cells/L and 2269 UI/mL, respectively. Spirometry results from the study's participants indicated an obstructive pattern in about 80% of cases. The most typical radiological abnormality observed was bronchiectasis, followed by parenchymal opacities. In conclusion, when treating asthma that is challenging to control, the diagnosis of ABPA must be taken into account. Delay in diagnosis might result in declining lung function, worsening asthma control, possibly irreversible alterations, greater treatment costs, and declined quality of life.

PILOT STUDY ON EFFECTIVENESS OF SIDDHA MEDICINES SOMBU THEENEER (INTERNAL) AND PEENISATHIRKU THAILAM (EXTERNAL) IN THE MANAGEMENT OF PEENISAM (SINUSITIS)

Background: Peenisam (sinusitis) is a widespread condition, and patients are visiting Ayothidass Pandithar Hospital, National Institute of Siddha, to manage this condition. The signs and symptoms of peenisam (sinusitis) are mentioned in Siddha literature Yugi vaithya chinthamani, such as lacrimation, nasal block, headache, rhinorrhea, cough, absence of taste, may be correlated with maxillary sinusitis in biomedicine. Objectives: To evaluate the clinical effectiveness of Siddha formulations Sombu theeneer (internal) and Peenisathirku thailam (external) in the management of sinusitis by using Adelaide Disease Severity Score (ADSS) and to observe changes in clinical lab parameters, total count, differential count, erythrocyte sedimentation rate, absolute eosinophil count and serum immunoglobulin E pre and post-treatment. Methods: An open Non-Randomised clinical trial with a sample size of 10 patients diagnosed with Peenisam within the age limit of 18-60 years. The approval was obtained from Institutional Ethical Committee for conducting this clinical study with the IEC No: (25/11/2021; NIS/IEC/2021/MP-3). It was registered prospectively in the Clinical Trail Registry of India (CTRI Reg No: CTRI/2022/01/051045). The trial drug Sombu theeneer (internal) 30 ml BD with water after food and Peenisathirku thailam (external) were given for 48 days and two months follow up without the trial drug. Results: Biostatistical reports of ADSS scores and lab investigations before and after treatment were statistically analysed using paired t-tests. There was a significant reduction in both the ADSS.

Prolonged Itraconazole Therapy as Sole Treatment for Patients with Allergic Fungal Rhinosinusitis.

Currently, the mainstay of treatment for allergic fungal rhinosinusitis (AFRS) is surgical debridement along with topical or systemic steroids. However, prolonged systemic steroid therapy comes with side effects and is also sometimes contraindicated. Systemic antifungals have been used earlier as an adjunct to steroids or in refractory cases, but they have not been used as the sole primary treatment. To study the effectiveness of sole Itraconazole therapy in patients with AFRS by comparison of clinical, radiological, and biochemical parameters before and after treatment. Thirty-four patients diagnosed with localized sino-nasal AFRS were recruited and started on the tablet Itraconazole 200 mg orally twice daily for 3 months with q2weekly monitoring of liver function tests. The baseline clinical, radiological, and biochemical parameters were then compared with those after completion of 3 months of Itraconazole therapy. There was significant difference between all the parameters-clinical: SNOT-22 score (p < 0.001) and Meltzer endoscopy score (p < 0.001), radiological: Lund-Mackay score (p = 0.004) and 20-point CT score (p = 0.002), and biochemical: serum total IgE (p < 0.001), Aspergillus-specific IgE (p < 0.001), and absolute eosinophil count (p < 0.001). The clearance of the disease was more in anterior sinuses than the posterior ones. Prolonged Itraconazole can be given as sole therapy in AFRS, especially in patients for whom steroids are contraindicated or in those who are awaiting surgery. It can result in symptomatic and radiological improvement, but surgery still remains the definitive treatment option for AFRS for complete clearance of disease. 3 Laryngoscope, 134:545-551, 2024.

Sensitization pattern to various common allergens, using allergy skin prick test in children suffering from asthma and allergic rhinitis attending asthma outpatient department, at a tertiary care hospital in Central India

Background: Bronchial asthma is one of the most common chronic conditions of children. Allergy skin test, specific IgE levels can help to identify the triggers and better management. This observational study was carried to analyze the pattern of sensitization to various common allergens in children suffering from asthma and/ or allergic rhinitis at AIIMS, Raipur and to correlate sensitization with the various demographic parameters. Methods: Children between the age of one to 14 year diagnosed with asthma and/or allergic rhinitis were enrolled. They were subjected to skin prick test (SPT) using 18 common antigens. Induration more than 3mm than the negative control was considered as positive test. Results: 70 patients with an average age of 9.1 year were enrolled. 46 were males. Almost 80% (56) patients had sensitization to at-least one antigen tested. Highest sensitization was observed for cockroach mix 33 (58.92%) followed by Dermatophagoides farinae 18 (32.14%) and grain dust rice 16 (28.57%%). Sensitization was more in children with history of asthma in family (OR=2.37), residing near main road (OR=2.4), and in nuclear family (OR=1.54). There was no relation of SPT positivity with absolute eosinophil count (p=0.45, OR=0.41), family h/o allergic rhinitis (p=1.0, OR=0.86) and atopic dermatitis (p=1.0, OR=0.81). Statistically significant difference observed in the positivity of SPT in relation to severity of illness. (p=0.01, OR=0.162). Conclusions: Sensitization rate was high (80%) with cockroach mix being the commonest antigen. Family history of asthma, residence near main road and severity of illness were associated with higher sensitization.

A Study on the Significance of Nasal Smear Eosinophil Count and Blood Absolute Eosinophil Count in Patients with Allergic Rhinitis of Varied Severity of Symptoms.

The online version contains supplementary material available at 10.1007/s12070-023-03945-5.

Serum hydrogen sulphide levels in acute asthmatic children: a case control study

BackgroundIt’s thought that respiratory epithelium-produced reduced hydrogen sulphide (H2S) plays a role in the pathophysiology of acute asthma. In this case–control research, blood H2S levels were examined between matched acutely asthmatic children and non-asthmatic controls. The grade of acute asthma, vital signs and absolute eosinophilic count in the asthmatic children were likewise associated with the blood H2S level.MethodsForty Egyptian asthmatic children had visited the emergency room and forty age- and sex-matched non-asthmatic controls had their blood H2S levels measured using enzyme-linked immunosorbent assay (ELISA).ResultsThe serum H2S in the two groups did not differ statistically significantly. Serum H2S and respiratory rate showed a moderately significant inverse connection (r = -0.325, p = 0.041). However, serum H2S and other clinical or laboratory variables exhibited no meaningful relationships. Patients' absolute and percentage eosinophil counts were considerably higher than healthy controls. Serum H2S exhibited a sensitivity of 50% and a specificity of 32.5% for identifying children with acute asthma from non-asthmatic children.ConclusionChildren with asthma and those without asthma had similar serum H2S levels. It has a lousy relationship with respiratory rate. It is indicated that it is an inadequate screening and diagnostic tool since it has low sensitivity (50%) and specificity (32.5%) in differentiating acute asthmatic children.

Mepolizumab exerts crucial effects on glucocorticoid discontinuation in patients with eosinophilic granulomatosis with polyangiitis: a retrospective study of 27 cases at a single center in Japan

ObjectivesTo investigate the efficacy of mepolizumab in patients with eosinophilic granulomatosis with polyangiitis (EGPA) and factors contributing to glucocorticoid (GC) discontinuation.MethodsWe retrospectively studied EGPA patients treated with mepolizumab who were on GC at the time of induction of mepolizumab, at Japanese single center as of January 2023.Patients were classified into those who were able to discontinue GC at the time of the investigation (GC-free group) and those who continued (GC-continue group). Patient characteristics at the time of EGPA diagnosis (age, gender, absolute eosinophil counts, serum CRP level, serum IgE level, Rheumatoid factor (RF) / anti-neutrophil cytoplasmic antibody (ANCA) positivity, presence of asthma, affected organ, Five factor score (FFS), Birmingham Vasculitis Activity Score (BVAS) and characteristics at the time of mepolizumab induction (daily prednisolone dose, concomitant immunosuppressive maintenance therapy at the mepolizumab induction, prior history of GC pulse therapy, concomitant immunosuppressive therapy for remission induction,), history of relapse before mepolizumab induction and the duration of mepolizumab treatment were compared.We also followed the clinical indicators (absolute eosinophil counts, CRP and IgE levels, BVAS, Vascular Damage Index (VDI)) and daily prednisolone dosage at the EGPA diagnosis, at the mepolizumab induction and at the survey.ResultsTwenty-seven patients were included in the study. At the time of the study, patients had received mepolizumab for median 31 months (IQR, 26 to 40), the daily prednisolone dose was median 1 mg (IQR, 0 to 1.8) and GC-free was achieved in 13 patients (48%). Among clinical indicators that have improved by conventional therapy before the induction of mepolizumab, eosinophil counts, GC doses and BVAS have successively shown significant reductions throughout the observation period both GC-free and GC-continue. Of the GC-free patients, 7 were ANCA positive and 12 had FFS1 or more. Univariate analysis showed that the absolute eosinophil counts at diagnosis was significantly higher in the GC-free group (median 8165/µl (IQR, 5138 to 13,409) vs. 4360/µl (IQR, 151 to 8380), P = 0.037) and significantly fewer patients presented with gastrointestinal lesions (2 (15%) vs. 8 (57%), P = 0.025), while multivariate analysis showed no significant differences. Mepolizumab treatment significantly improved VDI in the GC-continue group (P = 0.004).ConclusionsAfter three years of treatment with mepolizumab, approximately 50% of patients with EGPA achieved GC-free status. GC could be discontinued even in severe cases and ANCA-positive cases. Although multivariate analysis did not extract any significant factors contributing to achieving GC-free, we found that improvement in eosinophil counts and BVAS led to GC reduction, resulted in protection of organ damages in both the GC-free and continuation groups. The significance of achieving GC-free remission in EGPA patients was demonstrated.

Evaluation of the Association Between Allergic Rhinitis and Middle Ear Dysfunction: A Clinicopathological Study.

The association between allergic rhinitis and otitis media with effusion (OME) has not yet been well studied in the Indian population. In our study, we have attempted to assess the role of nasal cytology on allergic rhinitis symptomatology and on middle ear dysfunction, and the diagnosis was established by symptomatology, AEC, and a nasal smear for eosinophils. The present study is a single-centre, hospital-based observational study and was conducted at the Department of Otorhinolaryngology and Head-Neck Surgery (All India Institute of Medical Sciences [AIIMS], Bhopal) among patients with symptoms of allergic rhinitis. The ENT examination included anterior rhinoscopy/diagnostic nasal endoscopy (zero-degree endoscope) along with otoscopy to examine the ear and nose. A nasal smear from the inferior turbinate of the nasal cavity was taken and then examined under a microscope to find out the percentage of eosinophils. The chi-squared test was used for group comparisons of categorical data. Statistical significance was kept at p < 0.05. In this study, out of 126 subjects with allergic rhinitis, 62 (49.2%) had middle ear dysfunction. The most prevalent middle ear pathologies were eustachian tube dysfunction (ETD; 28 cases, 22%), chronic otitis media (COM [16.6%]), OME (5.5%), and acute otitis media (AOM [4.5%]). ETD made up 45.1% of the ear diseases, with COM (33.87%), OME (11.29%), and AOM (9.6%) following. The mean value of absolute eosinophil count (AEC) among the allergic rhinitis participants (n = 32) was found to be 392.42. Absolute eosinophilia was present in 10 patients out of the 32 subjects being tested. Middle ear pathology was found in 7 of the 10 subjects found positive for absolute eosinophilia. Among the ear pathologies found in the participants (n = 7), the most common were ETD and OME (n = 5). There was no correlation between nasal smear cytology and the severity of nasal symptoms or middle ear disease. The majority of the participants were in nasal eosinophil grade I and showed sneezing as the most common nasal symptom and COM as the most common middle ear pathologic manifestation.

Strongyloides coinfection in COVID-19 patients treated with corticosteroids: A systematic review.

The COVID-19 pandemic linked to the virus SARS-CoV-2, which began in China, affected ∼765 million people as of 30 April 2023. The widespread use of corticosteroids for the symptomatic treatment of COVID-19 could lead to the reactivation of infections of opportunistic pathogens, including Strongyloides. We sought to determine the clinical symptoms and demographic characteristics of SARS-CoV-2-Strongyloides co-infection, particularly in patients with severe disease and being treated with immunosuppressive drugs. To do this, we undertook a systematic review of the literature, and searched public accessible scientific databases-the Web of Science, Scopus, PubMed/Medline and Embase -for eligible studies (1 December 2019 to 30 August 2022). The review protocol is registered in PROSPERO (CRD42022377062). Descriptive statistical analyses were used to present the clinical and laboratory parameters of the co-infection; for this, we calculated prevalence using the following formula: positive cases/total number of cases×100. Of a total of 593 studies identified, 17 studies reporting 26 co-infected patients met the criteria for inclusion in this review. The median age of these patients was 55.14years. Most of cases (53.8%) were treated with dexamethasone, followed by methylprednisolone (26.9%). Eighteen of 26 patients were immigrants living in European countries or the USA; most of these immigrants originated from Latin America (58%) and South-East Asia (11%). The commonest symptoms of co-infection were abdominal pain (50%), fever (46.1%), dyspnoea (30.7%) and cough (30.7%), and frequently reported laboratory findings were high absolute eosinophil count (38.4%), high white blood cell count (30.7%), high C-reactive protein (23.0%) and high neutrophil count (19.2%). Two of the 26 patients (7.7%) had fatal outcomes. Most of the SARS-CoV-2-Strongyloides coinfected cases were immigrants living in developed countries, emphasising the need for clinicians in these countries to be aware of clinical and laboratory parameters associated with such co-infections, as well as the key importance of rapid and accurate diagnostic tests for timely and effective diagnosis and patient management.

Frequency of PDGFRA, PDGFRB and FGFR1 Gene Rearrangements in Patients with Eosinophilia and Their Clinico-Haematologic Parameters

Objective: To determine the frequency and clinico-haematological features of PDGFRA, PDGFRB and FGFR1 gene rearrangements in patients with persistent Eosinophilia using Fluorescence in situ hybridization.&#x0D; Study Design: Cross-sectional study.&#x0D; Place and Duration of Study: Department of Hematology, Armed Forces Institute of Pathology, Rawalpindi Pakistan, from Dec 2018 to Dec 2019.&#x0D; Methodology: All Patients who presented to AFIP having absolute eosinophil count &gt;1.5x109/L persistent for over six months or with Myeloid or Lymphoid neoplasms with persistent Eosinophilia were studied. Patients having reactive Eosinophilia and those on treatment were excluded. Interphase FISH studies were performed. In addition, 2.5ml of sodium heparin blood was taken. After the denaturation of DNA, slides were set up according to standard protocol. FIP1L1/CHIC2/PDGFRA dual colour probe was applied for PDGFRA, 5q32 PDGFRA break apart probe for PDGFRB and XL FGFR1 break apart probe for FGFR1 gene rearrangement.&#x0D; Results: A total of 60 patients were included in the study. Of these, 50(83.3%) were males, and 10(16.7%) were females, with an average absolute Eosinophilia count of 5.92±7.10x109/L. The only rearrangement detected in patients with Eosinophilia was FIPILI-PDGFRA gene fusion, detected in 20% of the patients. No other rearrangement was found.&#x0D; Conclusion: PDGFRA, PDGFRB and FGFR1 mutations are rare yet most prominent in patients with clonal Eosinophilia. About 80% of eosinophilic patients were found to have idiopathic Eosinophilia, which requires further consideration to address the disease prevalence.

#6795 DISSEMINATED STRONGYLOIDES INFECTION IN A PATIENT WITH IGA NEPHROPATHY ON IMMUNOSUPPRESSIVE MEDICATIONS

Abstract Background and Aims Immunosuppressive medications such as high dose steroids and antimetabolites are frequently used in glomerulonephritis. However, use of these medications is usually associated with various adverse effects. Among the drawbacks of immunosuppressive therapy, the risk of reactivation of latent infections, including parasitic infestations, is to be considered. Method Case report. Results Our case is a 28 year old male patient who was diagnosed as a case of IgA nephropathy 7 months back with M1E1S1T1C0 lesions with a serum creatinine of 1.7 mg/dL and eGFR of 56 ml/min/1.73 m2. He was started on prednisolone (40mg daily) and mycophenolate mofetil (1000mg twice daily) for 1 month. He presented with us with diarrhea. He was treated with IV fluids and mycophenolate mofetil was stopped. After two weeks, he was readmitted with a 4-day history of fever, vomiting, and epigastric pain. On examination, he showed mild epigastric tenderness, normal vitals. The laboratory investigations on admission showed hemoglobin-15 g/dL, total leucocyte count-8600, eosinophilia with absolute eosinophil count 1900/ mm3, urea-92 mg/dL, creatinine-2 mg/dL. ECG showed sinus tachycardia, and HRCT chest revealed bilateral ground glass opacities and a calcified nodule in the left upper lobe. Liver function test was normal with normal amylase and calcium level. Blood culture was sterile. Ultrasound abdomen showed a bilateral raised Eco pattern in kidneys rest were normal. Upper GI endoscopy revealed diffuse edema, erythema, and superficial ulceration in duodenum and biopsy was taken. The duodenal biopsy showed features of strongyloidiasis stercoralis (Figure 1). Bronchoesophageal lavage was done which revealed strongyloidiasis stercoralis larvae. Meanwhile, the patient developed subacute small bowel obstruction with abdominal x ray showing multiple air fluid levels and CT scan showed features of small bowel obstruction with transition at mid-ileal level secondary to short segment thickening. Small bowel obstruction was relived with conservative mangement with ryles tube decompression and enemas. He was diagnosed with disseminated strongyloidiasis and treated with ivermectin for 14 days with full recovery Conclusion Our case signifies need of awareness among clinicians of the risk of disseminated strongyloidiasis as a complication of the treatment with immunosuppressive medications even in non-endemic areas.

The Evaluation of Laboratory Parameters as Predictors of Disease Severity and Mortality in COVID-19 Patients: A Retrospective Study From a Tertiary Care Hospital in India.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects and alters various laboratory parametersthat are predictors of disease severity and mortality, and hence, their prompt identification can aid in patient triaging and resourceallocation. Objectives A retrospective study was conducted on 7416 admitted coronavirus disease 2019 (COVID-19) patients from 20 March 2020 to 9August 2021 to identify crucial laboratory biomarkers as predictors of disease severity and outcome; also, their optimal cutoffs were also calculated. A comparison of laboratory markers between both COVID-19 waves was also performed. Results The majority of patients had mild disease (4295/7416, 57.92%), whereas 1262/7416 (17.02%) had severe disease. The overall fatal outcome was reported in 461 (6.22%) patients. Predictors for mortality were age (>52 years), albumin/globulin (A/G) ratio (≤1.47), chloride (≤101 mmol/L), ferritin (>483.89 ng/mL), lactate dehydrogenase (LDH) (>393 U/L), procalcitonin (>0.10 ng/mL), interleukin-6 (IL-6) (>8.8 pg/mL), fibrinogen (>403 mg/dL), international normalized ratio (INR) (>1.18), and D-dimer (>268 ng/mL). Disease severity predictors were neutrophils (>81%), lymphocyte (≤25.4%), absolute lymphocyte count (ALC) (≤1.38×103/µL), absolute eosinophilcount (AEC) (≤0.03×103/µL), total bilirubin (TBIL) (≥0.51 mg/dL), A/G ratio (≤1.49), albumin (≤4.2 g/dL), ferritin (≥445.4 mg/dL), LDH (≥479 U/L), IL-6 (≥28.6 pg/mL), C-reactive protein/albumin (CRP/ALB) ratio (≥1.78), D-dimer (≥237 ng/mL), and fibrinogen (≥425 mg/dL). The majority of patients admitted in the second wave were older and had severe disease, increased fatality, and significantly deranged laboratory parameters than first wave patients. Conclusion Our findings suggested that several biomarkers are crucial for both severe disease and mortality in COVID-19 patients. Ferritin, LDH, IL-6, A/G ratio, fibrinogen, and D-dimer are important biomarkers for both severity and mortality, and when combined, they provide valuable information for patient monitoring and triaging. In addition to these, older age, INR, chloride, and procalcitonin are also significant risk factors for mortality. For severe COVID-19, TBIL, CRP/ALB, albumin, neutrophil percentage, lymphocyte percentage, ALC, and AEC are also important biomarkers. According to the study, the majority of the baseline laboratory parameters associated with COVID-19 mortality and severe diseasewere significantly higher during the second wave, which could be one of the possible causes for the high mortality rate in India during the second wave. So, the combination of all these parameters can be a powerful tool in emergency settings to improve the efficacy of treatment and prevent mortality, and the planningof subsequent waves should be done accordingly.

Bronchial thermoplasty improves cough hypersensitivity and cough in severe asthmatics

BackgroundCough is a troublesome symptom of asthma because it is associated with disease severity and poor asthma control. Bronchial thermoplasty (BT) may be effective in improving cough severity and cough-related quality of life in severe uncontrolled asthma. ObjectiveTo evaluate the efficacy of BT for cough in severe uncontrolled asthma. MethodsTwelve patients with severe uncontrolled asthma were enrolled in this study between 2018 May and March 2021 and arbitrarily divided into cough-predominant [cough severity Visual Analog Scale (VAS) ≥ 40 mm, n = 8] and typical asthma (cough VAS <40 mm, n = 4) groups. Clinical parameters, such as capsaicin cough sensitivity [C-CS: the concentrations to inhaled capsaicin required to induce at least two (C2) and five (C5) coughs], lung function, and type-2–related biomarkers (fractional nitric oxides and absolute eosinophil counts) and cough-related indices [cough severity VAS and the Leicester Cough Questionnaire (LCQ)] were evaluated before and 3 months after performing BT. ResultsBT significantly improved both cough-related indices and C-CS in the cough-predominant group. Changes in C-CS were significantly correlated with changes in the LCQ scores (C5: r = 0.65, p = 0.02 for all patients, and r = 0.81, p = 0.01 for the cough-predominant group). ConclusionsBT may be effective for cough in severe uncontrolled asthma by improving C-CS. However, further larger cohort studies are necessary to confirm the effect of BT for cough in asthma. Clinical trial registrationThis study was registered in the UMIN Clinical Trials Registry (Registry ID UMIN: 000031982).

Safety and Efficacy of Dexpramipexole in Eosinophilic Asthma (EXHALE): A randomized controlled trial

There is a need for new and effective oral asthma therapies. Dexpramipexole, an oral eosinophil-lowering drug, has not previously been studied in asthma. We sought to evaluate the safety and efficacy of dexpramipexole in lowering blood and airway eosinophilia in subjects with eosinophilic asthma. We performed a randomized, double-blind, placebo-controlled proof-of-concept trial in adults with inadequately controlled moderate to severe asthma and blood absolute eosinophil count (AEC) greater than or equal to 300/μL. Subjects were randomly assigned (1:1:1:1) to dexpramipexole 37.5, 75, or 150 mg BID (twice-daily) or placebo. The primary end point was the relative change in AEC from baseline to week 12. Prebronchodilator FEV1 week-12 change from baseline was a key secondary end point. Nasal eosinophil peroxidase was an exploratory end point. A total of 103 subjects were randomly assigned to dexpramipexole 37.5 mg BID (N= 22), 75 mg BID (N= 26), 150 mg BID (N= 28), or placebo (N= 27). Dexpramipexole significantly reduced placebo-corrected AEC week-12 ratio to baseline, in both the 150-mg BID (ratio, 0.23; 95% CI, 0.12-0.43; P< .0001) and the 75-mg BID (ratio, 0.34; 95% CI, 0.18-0.65; P= .0014) dose groups, corresponding to 77% and 66% reductions, respectively. Dexpramipexole reduced the exploratory end point of nasal eosinophil peroxidase week-12 ratio to baseline in the 150-mg BID (median, 0.11; P= .020) and the 75-mg BID (median, 0.17; P= .021) groups. Placebo-corrected FEV1 increases were observed starting at week 4 (nonsignificant). Dexpramipexole displayed a favorable safety profile. Dexpramipexole demonstrated effective eosinophil lowering and was well tolerated. Additional larger clinical trials are needed to understand the clinical efficacy of dexpramipexole in asthma.

Sex differences in prognostic utility of peripheral eosinophil count in first-line immune checkpoint therapy against metastatic NSCLC.

9067 Background: To date, few studies have associated elevated Absolute Eosinophil Count (AEC) with improved outcome to a single agent immune checkpoint inhibitor (ICI) as first or subsequent line of therapy in patients with NSCLC. Here, we investigated prognostic utility of AEC and the sex difference in patients undergoing standard-of-care first-line ICI with or without chemotherapy for metastatic NSCLC. Methods: This was a retrospective cohort study of 310 patients with Stage IV NSCLC treated with first-line ICI-based therapies (alone or in combination with chemotherapy) under IRB approved protocol 2021C0069. Demographic data are summarized in the table. Peripheral AEC measured by cells/microL was collected within 1 week before the start of therapy. Eosinophil count was evaluated in males and females by both descriptive statistics and Chi-squared test as a continuous and categorical variable, respectively. High level of baseline AEC was defined as 75th percentile (270 cells/microL). Overall Survival (OS) was plotted using the Kaplan-Meier method and p-values from log-rank test were reported. PD‐L1 was assessed by tumor proportion score (TPS) and classified into &lt; 1%, 1 to 49% and ≥ 50%. Results: 14% male vs 6% female patients were found to have peripheral eosinophilia (AEC ≥ 500) at the start of immunotherapy, p = 0.02. Patients with lower AEC had a median OS of 18.6 months vs 29.3 months in those with higher AEC ( p = 0.02, HR: 1.465, 95% Cl: 1.073-2.001). Patients with higher baseline AEC showed a sex difference, with median OS of 23.9 months in males vs NR median OS in females with over 60% survival at the time of last follow up ( p = 0.04, HR: 1.934, 95% Cl: 1.040-3.597). This difference was seen with ICI monotherapy ( p = 0.02, HR: 2.630, 95% Cl: 1.192-5.805), but not ICI with chemotherapy ( p = 0.83, HR: 1.116, 95% Cl: 0.4054-3.070). Higher AEC was associated with TPS ≥ 50% in both males and females ( p = 0.004 and 0.001, respectively), though no significant sex difference was observed. Conclusions: Our data highlight critical sex differences in interpretation of baseline AEC in patients on ICI therapy for metastatic NSCLC. While males have a higher frequency of peripheral eosinophilia, higher AEC correlates to improved OS predominantly in females. Further, this female-biased outcome is seen only with ICI monotherapy, even though higher AEC is associated with high PD-L1 expression in both sexes. Future studies are indicated to assess the longitudinal trend in eosinophil count as well as their active versus passive role in anti-tumor immunity and toxicity in the presence or absence of chemotherapy. [Table: see text]

Blood eosinophils as prognostic biomarkers for advanced urothelial carcinoma in patients treated with avelumab: First results of the MALVA study (Meet-URO 25).

e16570 Background: Platinum-based chemotherapies (CTs) represent the standard first-line treatment of advanced urothelial carcinoma (aUC). However, the development of resistance and toxicities to these regimens is responsible for poor progression-free survival (PFS) and overall survival (OS). Maintenance treatment with the programmed death-ligand 1 (PD-L1) inhibitor avelumab after initial response to CT improved significantly OS. Despite the survival advantage, only a limited percentage of patients (pts) benefits from immunotherapy. Therefore, prognostic/predictive factors for immunotherapy are needed. Studies carried out on small cohorts of pts with melanoma, renal cell cancer or lung carcinoma proved that eosinophil count or variations could be used as prognostic factors during immunotherapy. Thus, the aim of the present study is to evaluate eosinophil levels as potential biomarker for outcome among aUC pts enrolled in the MALVA (Maintenance with AVeLumAb in advanced urothelial neoplasms in response to first-line CT: an observational retrospective and prospective study) ongoing study (Meet-URO 25). Methods: The MALVA study is an ongoing real-life multicentric retro-/prospective observational study on aUC pts receiving avelumab maintenance after response to platinum-based first-line CT. The co-primary endpoints are OS and PFS. We present here data of the first 100 enrolled aUC pts who received avelumab as maintenance therapy after response to platinum-based CT between January 2021 and January 2023. Absolute Eosinophil Counts (AEC) were registered at baseline (week 0) and at time of the first tumor assessment (week 12). This study aims to evaluate whether the AEC could be a predictive biomarker of efficacy in pts with aUC treated with avelumab. Results: One-hundred pts (median age, 72 years), 71.4% of whom were men, were enrolled (data cut off, January 2, 2023). Median follow-up time was 8.5 months. Median duration of avelumab treatment was 5.9 months. Median PFS for the entire population was 8.7 months (95% CI; 5.7 months-not reached). Predefined subgroup analyses showed PFS and OS improvement (5.1 months vs NR, p = 0.0031; 12.9 months vs NR, p = 0.056 respectively) in pts with high AEC at week 0 vs low AEC pts. Additionally, a pilot analysis was conducted for 34 pts, for whom PFS and OS were stratified by AEC at first tumor assessment (week 12). PFS was longer (6.4 months vs NR, p = 0.045) for pts with high AEC vs low AEC pts. Conclusions: In order to optimize treatment efficacy in aUC, reliable biomarkers are required. In this study, we provide data from a homogeneous cohort investigating the relevance of eosinophils in aUC pts receiving avelumab, suggesting that AEC could be an easily accessible and reproducible prognostic biomarker that warrants further studies.

Effectiveness of Traditional Chinese Medicine on coronavirus disease 2019 in 92 patients: a retrospective study.

To investigate the antipyretic effect of early treatment with Traditional Chinese Medicine (TCM) on coronavirus disease 2019 (COVID-19) patients. We retrospectively analyzed 369 patients from January 26th, 2020 to April 15th, 2020, who had been diagnosed with COVID-19. Among 92 eligible cases, 45 cases were identified as treatment group Ⅰ ( 45) and 47 cases were identified as treatment group Ⅱ. Patients in the treatment group Ⅰ were treated with TCM herbal decoction within 5 d after admission. Patients in the treatment group Ⅱ were treated with TCM herbal decoction after the 6th admission day. The onset time of antipyretic effect, the antipyretic time, the time of negative oropharyngeal swab nucleic acid conversion, and the changes of cell count in blood routine test were compared. The treatment group I showed shorter average antipyretic duration (4 7 d; <0.05), and shorter average time for polymerase chain reaction (PCR) nucleic acid test results to turn negative (7 11 d; <0.05) than the treatment group II. For patients ( 54) with body temperature>38 ℃, patients in the treatment group I had shorter median onset time of antipyretic effect than those in the treatment group II (3 4 d; <0.05). The absolute lymphocyte (LYMPH) count and absolute eosinophil (EOS) count on the 3rd day after admission and the neutrophil/lymphocyte ratio on the 6th day after admission of patients in the treatment group I were notably different from those in the treatment group II at the same time point (0.05). Based on Spearman's rank correlation analysis, the change of body temperature on the 3rd day after admission was positively correlated with the increase of EOS count and the increase of EOS count and LYMPH counts on the 6th day after admission (0.01). Early TCM intervention within 5 d after hospital admission shortened the onset time of antipyretic effect and fever duration of COVID-19 patients, reduced the time required for PCR test results to turn negative. Moreover, early TCM intervention also improved the results of inflammatory markers for COVID-19 patients. LYMPH and EOS counts can be used as indicators of TCM antipyretic effect.