The role of viral infections in pulmonary exacerbations of patients with non-cystic fibrosis bronchiectasis: A systematic review

BackgroundBronchiectasis is a cause of increased morbidity of the respiratory system. Exacerbations among patients with non-CF (cystic fibrosis) bronchiectasis result in reduced pulmonary function and poor quality of life. While the role of bacteria in triggering exacerbations in patients with non- CF bronchiectasis has been well studied, little is known about viral infections in these patients. We aimed to review the evidence on the role of respiratory viruses in the exacerbations of non-CF bronchiectasis.MethodsRelevant literature was searched on the MEDLINE/PubMed database. Seven studies satisfied the criteria and were included in this review.ResultsAccording to the included articles, respiratory viruses are often identified in exacerbations of patients with non-CF bronchiectasis with the most frequent being human rhinovirus and influenza viruses. When a virus is isolated during an exacerbation patients have more symptoms from the upper respiratory tract. One study showed that detection of Epstein- Barr virus among patients with non-CF bronchiectasis is correlated with faster reduction of pulmonary function and progression of the disease.ConclusionViruses seem to have a role in the exacerbation of patients with non-CF bronchiectasis. However, the exact nature and importance of this role remain elusive. Viruses are also isolated during the stable period of the disease. Further well-designed studies are necessary to clarify this complex issue.     

Prevalence of viral infection in acute exacerbation of interstitial lung diseases in Japan

BackgroundFatal acute exacerbation of interstitial lung diseases is often accompanied by indicators of infection such as fever, cough, and sputum. Although viral infection can contribute to acute exacerbation of interstitial lung diseases, few studies have identified a relationship between acute exacerbations and viral infections. The present study aimed to prospectively clarify the role of viral infection in patients showing acute exacerbation of interstitial lung disease in Japan.MethodsNasopharyngeal swab specimens were collected from patients with acute exacerbation of interstitial lung disease between May 2017 and February 2019. Respiratory viruses were detected by the Luminex xTAG Respiratory Viral Panel FAST v2 RUO kit and the BioFire FilmArray Respiratory Panel assay.ResultsThree of 29 patients demonstrated respiratory viral infection during acute exacerbation of interstitial lung diseases. The infectious agents were identified as respiratory syncytial virus, respiratory syncytial virus and influenza A virus, and influenza A virus and rhino/enterovirus in the three patients, respectively.ConclusionsThese results suggest that viral infection did not frequently induce acute exacerbation of interstitial lung diseases in Japan.     

Efficacy of immunoglobulin replacement therapy and azithromycin in severe asthma with antibody deficiency

BackgroundAlthough antibody deficiency (AD) is a well-known cause of recurrent respiratory infections, there are few data on its impact in adults with asthma. The objective of the present study was to assess outcomes in adults with severe asthma and AD after treatment with either azithromycin or subcutaneous immunoglobulins (SCIg).MethodsWe performed a 5-year, prospective, observational, two-centre study of adults with severe asthma and AD in France. Bronchiectasis was ruled out by high-resolution computed tomography. Patients were treated for one year with either azithromycin (250 mg every other day) or SCIg (0.4–0.6 g/kg/months, weekly). All patients were evaluated for exacerbations, asthma control and lung function at baseline and then one year after treatment initiation.ResultsThirty-nine patients with severe asthma were included in the study: 14 had been treated with azithromycin and 25 had been treated with SCIg. Before the initiation of treatment for AD, all patients had an Asthma Control Questionnaire (ACQ-7) score > 1.5 (mean ± SD: 2.71 ± 0.53) despite treatment at GINA step 4 or 5, and had a high exacerbation rate requiring oral corticosteroids and/or rescue antibiotics (∼7.2 ± 2.1/patient/year). One year after treatment initiation, we observed a significantly higher FEV1 (mean: 0.18 ± 0.22 L) and ACQ-7 score (1.26 ± 0.68), and a significantly lower exacerbation rate (1.63 ± 1.24/patient/year).ConclusionsTreatment of AD dramatically improved asthma outcomes - suggesting that adults with severe asthma and recurrent respiratory infections should be screened and (if appropriate) treated for AD.     

Impact of coronavirus disease 2019 on respiratory care in Japan: A nationwide survey by the Japanese Respiratory Society

BackgroundCoronavirus disease 2019 (COVID-19) has spread worldwide since 2020, placing a huge burden on medical facilities. In the field of respiratory medicine, there has been a decrease in the number of patients. While many pulmonologists have been receiving patients with COVID-19, the actual effects on respiratory care have not been elucidated. Therefore, we conducted this study to clarify the effects of COVID-19 on medical care in the field of respiratory medicine.MethodsWe conducted a questionnaire survey among 749 hospitals belonging to the Board-Certified Member system of the Japanese Respiratory Society on the effects of COVID-19 from November 2021.ResultsResponses were obtained from 170 hospitals (23%), in approximately 70% of which the respiratory medicine department was the main department involved in managing COVID-19. The number of spirometry and bronchoscopy tests decreased by 25% and 15%, respectively, and the number of both outpatients and inpatients decreased in 93% of hospitals. Among respiratory diseases, the number of patients hospitalized for usual pneumonia, bronchial asthma, and chronic obstructive pulmonary disease decreased greatly by 30%–45%. In 62% of hospitals, the biggest effect of the COVID-19 pandemic was the greater burden in terms of the clinical workload due to COVID-19.ConclusionsAlthough the number of tests and non-COVID-19 outpatients and inpatients decreased in respiratory medicine departments during the COVID-19 pandemic, the workload increased due to COVID-19, resulting in a great increase in the clinical burden.     

Overweight improves long-term survival in Japanese patients with asthma

BackgroundObesity is a risk factor for severe and difficult-to-treat asthma. However, the impact of different physiques on long-term outcomes is poorly understood. We aimed to investigate the correlation between obesity and asthma-associated long-term mortality in Japanese adults.MethodsFrom the data on 3146 individuals with air pollution-related respiratory diseases in the Omuta City Air Pollution-Related Health Damage Cohort Program, 697 adult patients with asthma were analyzed. Hazard ratios for long-term all-cause and respiratory disease -related mortality were compared in patients with different physiques using the Cox proportional hazard models. The classification of physiques was based on the WHO obesity criteria.ResultsOf the 697 patients, 439 died during the median observation period of 26.3 years. The number (% of total) of underweight, normal-weight, pre-obese, and obese class I–III individuals were 75 (10.8%), 459 (65.9%), 140 (20.1%), and 23 (3.3%), respectively. The Cox proportional hazard model (adjusted hazard ratio [95% confidence interval], P value) showed that pre-obese group had a significantly reduced risk for all-cause (0.65 [0.51 to 0.83], P < 0.05) and respiratory disease (0.55 [0.37 to 0.81], P < 0.05)-related mortality related to normal-weight group.ConclusionsOur cohort program demonstrated that being slightly overweight may reduce the risk of long-term mortality in patients with asthma. However, the influence of obesity on long-term outcomes remains unclear in asthma, because of the small number of obese patients included in our study. Our findings suggest that interventions, including nutrition and exercises, should be provided to Japanese patients with asthma.     

Association of longitudinal changes in quality of life with comorbidities and exacerbations in patients with severe asthma

BackgroundQuality of life (QoL) assessment is important in the management of severe asthma, and comorbidities and/or exacerbations may affect longitudinal QoL. However, there are few reports on the longitudinal assessment of QoL in patients with asthma over multiple years and its related factors. This study aimed to clarify the relationship of longitudinal changes in QoL with comorbidities and/or exacerbations during a prolonged observation period in patients with severe asthma.MethodsA total of 105 subjects who participated in the Hokkaido-based Investigative Cohort Analysis for Refractory Asthma (Hi-CARAT) with a six-year follow-up were analyzed. QoL was assessed annually, using the Standardized Asthma Quality of Life Questionnaire, and the subjects were divided into three groups: (1) persistently good QoL, (2) persistently poor QoL, and (3) fluctuating QoL. Assessed comorbidities comprised depression, gastroesophageal reflux disease, and excessive daytime sleepiness (EDS), a key symptom of obstructive sleep apnea.ResultsOf 105 subjects with severe asthma, 53 (50%) were classified in the persistently good QoL group, 10 (10%) in the persistently poor QoL group, and 42 (40%) in the fluctuating QoL group. The persistently poor QoL group was associated with shorter time to hospitalization due to exacerbation and the presence of multiple comorbidities. In addition, the presence of EDS was an independent contributor to the fluctuating QoL group compared to the persistently good QoL group.ConclusionsThe presence of multiple comorbidities and hospitalization due to exacerbation contribute to longitudinal changes in QoL in patients with severe asthma.     

Efficacy and safety of tezepelumab in patients recruited in Japan who participated in the phase 3 NAVIGATOR study

BackgroundTezepelumab, a human monoclonal antibody, blocks the activity of thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab reduced exacerbations by 56% compared with placebo in adults and adolescents with severe, uncontrolled asthma. This analysis evaluated the efficacy and safety of tezepelumab in NAVIGATOR patients recruited in Japan.MethodsNAVIGATOR was a phase 3, multicenter, randomized, double-blind, placebo-controlled study. Patients (12–80 years old) were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Endpoints assessed included: the annualized asthma exacerbation rate (AAER) over 52 weeks (primary endpoint) and the change from baseline to week 52 in pre-bronchodilator forced expiratory volume in 1 s (FEV₁) and Asthma Control Questionnaire (ACQ)-6 score. The safety of tezepelumab was also assessed.ResultsOverall, 97 patients recruited in Japan were randomized (tezepelumab, n = 58; placebo, n = 39). The AAER over 52 weeks was 1.54 (95% confidence interval [CI]: 0.90, 2.64) with tezepelumab compared with 3.12 (95% CI: 1.82, 5.35) with placebo (rate ratio: 0.49 [95% CI: 0.25, 0.99]; 51% reduction). For tezepelumab and placebo, the least-squares mean (standard error) change from baseline to week 52 for pre-bronchodilator FEV₁ was 0.23 (0.06) L and 0.19 (0.07) L and the ACQ-6 score was ?1.12 (0.15) and ?0.97 (0.19), respectively. The frequency of adverse events was similar between treatment groups (tezepelumab, 86.2%; placebo, 87.2%).ConclusionsTezepelumab reduced exacerbations compared with placebo, and was well tolerated, in NAVIGATOR patients with severe, uncontrolled asthma recruited in Japan.     

Real-world treatment and health care resource use among severe asthma patients in Japan

BackgroundThere are limited studies on healthcare resource use (HCRU) among adult asthma patients in Japan using real-world evidence, and analysis on acute treatment and associated costs stratified by disease severity is further limited. This study aimed to characterize the disease burden of severe asthma patients in Japan in terms of HCRU and comorbid medical conditions, with particular interest in oral corticosteroid (OCS) dependency.MethodsThis retrospective cohort study of asthma patients used data from a claims database of diagnosis procedure combination hospitals in Japan. The severe asthma cohort included patients treated with OCS for more than 180 days in one year before the index date, with at least one asthma diagnosis claim. Comorbidity and drug use in the look-back period, HCRU, assumed OCS-related adverse events, and asthma exacerbations in the follow-up period were analyzed.ResultsCosts associated with the treatment of severe asthma were approximately twice that of mild/moderate asthma, and the annual median cost of patients hospitalized due to asthma reached ¥448,000 (USD $4073). Annual asthma exacerbation rate was higher in the severe asthma cohort than in the mild/moderate cohort. Patients with longer OCS use in the previous year had higher risks of secondary adrenal insufficiency, osteoporosis, and pneumonia in the following year.ConclusionsOCS use among asthma patients in Japan incurred greater medical and economic burden. Better understanding of the disease characteristics including the severity of asthma and appropriate management of disease burden will lead to more optimal use of healthcare resources in Japan.     

Determination of the cutoff values of Th2 markers for the prediction of future exacerbation in severe asthma: An analysis from the Hokkaido Severe Asthma Cohort Study

BackgroundWe recently reported that severe asthma patients with frequent exacerbations showed high blood eosinophil counts (Eo) and fractions of exhaled nitric oxide (FeNO) compared with non-exacerbators. However, we did not determine exact cutoff values related to exacerbation. The aim of this study was to determine the cutoff values of Eo and FeNO that could be related to the exacerbation of severe asthma. We also aimed to confirm the clinical utility of Th2 markers related to exacerbation.MethodsThis study included 105 severe asthma patients who completed a three-year follow-up of a severe asthma cohort study, including smokers. Three Th2 markers were selected, viz., Eo, FeNO, and positive atopic status. Regarding Eo and FeNO, we determined the cutoff values for the definition of “positive” Th2 features using receiver operating characteristic curve analyses, based on the comparisons between frequent exacerbators and other patients.ResultsThe cutoff values for positive Th2 features were Eo ≥ 250 cells/μL and FeNO ≥31 ppb. Sixteen patients (15.2%) had no Th2 features, 40 (38.1%) had one, 25 (23.8%) had two, and 24 (22.9%) had three. A high number of positive Th2 features was significantly associated with exacerbation frequencies over three years (p < 0.05). Similarly, compared to patients with one or no Th2 features, those with three Th2 features had a significantly higher probability of having more than one exacerbation (p < 0.05).ConclusionsThe cutoff values determined in the current analysis were good predictors of future exacerbations in severe asthma patients.     

Clinical significance of heart rate variability for the monitoring of cardiac autonomic neuropathy in end-stage renal disease patients

Background and aimsThe aim of this study is to determine whether the measurement of continuous heart rate variability (HRV) is useful in the evaluation of cardiac autonomic neuropathy (CAN) in end-stage renal disease (ESRD) patients.Methods and resultsThis cross-sectional study was performed at Seoul St. Mary's hospital between June 2017 and February 2018. Seventy-seven ESRD patients, and 29 healthy controls (HCs) were asked to wear a continuous ambulatory HRV monitor for 24 h. General cardiac function was evaluated using transthoracic echocardiogram (TTE), pulse wave velocity (PWV), coronary calcium scoring (CCS), and 24-h ambulatory blood pressure monitoring (ABPM). HRV parameters of ESRD patients and HCs, and the correlation of HRV parameters with cardiovascular screening methods were observed. All HRV parameters were significantly decreased in ESRD patients compared to HCs (P < 0.001). In the correlation analysis between TTE results and HRV parameters, 24-h standard deviation of all N–N intervals (24SDNN), 24-h standard deviation of sequential 5-min N–N interval means (24DANN) and Low Frequency Power/High Frequency Power (LF/HF) ratio showed negative correlations with E/e’, LAVI and TR velocity which are representative indices for the diastolic function of the heart (P < 0.05). HRV parameters showed negative correlations with baPWV, CCS, and 24-h ABPM results as well (P < 0.05). Hemoglobin and serum albumin showed positive correlations with HRV parameters, and glucose, BUN, creatinine, and iPTH levels showed negative correlations (P < 0.05).ConclusionContinuous HRV monitoring may be a useful tool for the evaluation of CAN in ESRD.     

Frailty and muscle weakness in elderly patients with asthma and their association with cumulative lifetime oral corticosteroid exposure

BackgroundFrailty is a geriatric syndrome of age-related physiological decline, which is associated with higher mortality and decreased healthy life expectancy, and muscle weakness is one of the presentations of frailty. We investigated an association between lifetime oral corticosteroid (OCS) exposure with frailty and muscle weakness among elderly patients with asthma.MethodsWe studied 203 consecutive elderly outpatients with asthma aged ≥60 years old. They were classified into three groups according to their cumulative lifetime OCS dose (lifetime non-users, lower-dose users, and higher-dose users), which was retrospectively estimated from the response to a structured questionnaire. The prevalence of frailty determined by the Kihon Checklist was compared between the three groups. Hand-grip strength, and lean mass index were also measured as markers of muscle strength.ResultsThirty-seven percent of the patients studied were considered frail. Higher cumulative lifetime OCS exposure was associated with a significantly higher prevalence of frailty (33% in lifetime non-users, 59% in lower-dose users, and 68% in higher-dose users; P for trend <0.005). This was also associated with lower hand-grip strength in both sexes (P for trend; 0.012 in men, and 0.020 in women), and lower lean mass index in men (P for trend 0.002). However, current doses of OCS were not significantly associated with these outcomes.ConclusionsCumulative lifetime OCS exposure was associated with a higher prevalence of frailty and muscle weakness. These findings emphasize the importance of minimizing lifetime OCS exposure for the prolongation of healthy life expectancy in patients with asthma.     

Dupilumab efficacy and safety in Japanese patients with uncontrolled,moderate-to-severe asthma in the phase 3 LIBERTY ASTHMA QUEST study

BackgroundIn the LIBERTY ASTHMA QUEST (ClinicalTrials.gov: NCT02414854) study, dupilumab 200 mg and 300 mg every 2 weeks vs matched-volume placebo reduced severe asthma exacerbations and improved lung function (FEV₁), asthma control, and quality of life in patients with uncontrolled, moderate-to-severe asthma (N = 1902). Here, we examine the safety and efficacy of dupilumab in the subpopulation of Japanese patients who participated in QUEST (n = 114; 6%).MethodsEndpoints assessed were annualized severe exacerbation rates and the effect of treatment over the 52-week treatment period on FEV₁, asthma control, asthma-related quality of life, and markers of type 2 inflammation.ResultsIn Japanese patients, dupilumab 200 and 300 mg every 2 weeks vs matched placebo reduced severe asthma exacerbation rates by 44% (P = 0.33) and 75% (P = 0.03), respectively, and improved FEV₁ at Week 12 by 0.20 L (P = 0.05) and 0.17 L (P = 0.12). FEV₁ improvements were rapid (by Week 2) and sustained throughout treatment. Significant and/or numerical improvements vs placebo in asthma control and quality of life were also observed throughout treatment. For each endpoint, greater efficacy was observed in patients with elevated baseline levels of type 2 inflammatory biomarkers (blood eosinophils or FeNO). Dupilumab treatment significantly reduced levels of FeNO and total IgE, but not blood eosinophils.ConclusionsIn this subanalysis of QUEST, the efficacy and safety of dupilumab in Japanese patients was comparable to that observed in the overall intention-to-treat population, suggesting no variability in efficacy on the basis of Japanese ethnicity.(Funded by Sanofi and Regeneron Pharmaceuticals, Inc.; ClinicalTrials.gov number: NCT02414854)     

The impact of budesonide inhalation suspension for asthma hospitalization: In terms of length of stay,recovery time from symptoms,and hospitalization costs

BackgroundHospitalization is a major cause of medical expenditure for asthma. Budesonide inhalation suspension (BIS) may assist in reducing asthma-related symptoms in severe asthma exacerbation. However, its effectiveness for hospitalized patients remains poorly known. The objective of this study is to determine associations of BIS with asthma hospitalization.MethodsWe retrospectively analyzed 98 patients who were admitted to our hospital due to severe asthma exacerbation (24 treated with BIS in combination with procaterol) from April 2014 to January 2019. Length of stay, recovery time from symptoms (wheezes), and hospitalization costs were compared between the 2 groups according to clinical factors including the use of BIS and sings of respiratory infections (i.e. C-reactive protein, the presence of phlegm, and the use of antibiotics). Multivariate logistic regression analysis was performed to determine factors contributing to hospitalization outcomes.ResultsThe use of BIS was associated with shorter length of stay, faster recovery time from symptoms, and more reduced hospitalization costs (6.0 vs 8.5 days, 2.5 vs 5.0 days, and 258,260 vs 343,350 JPY). Signs of respiratory infection were also associated with hospitalization outcomes. On a multivariate regression analysis, the use of BIS was a determinant of shortened length of stay and reduced symptoms and medical costs for asthma hospitalization along with signs of respiratory infection.ConclusionsBIS may contribute to shorten length of hospital stay and to reduce symptoms and medical expenditure irrespective of the presence or absence of respiratory infection.     

Characterization of low adherence population in asthma patients from Japan using Adherence Starts with Knowledge-12

BackgroundAdherence Starts with Knowledge-12 (ASK-12) is a useful indicator of drug adherence. In this study, we analyzed patient background including social and psychological factors in a low-adherence group of patients with asthma defined using ASK-12.MethodsFrom a questionnaire survey for patients with asthma from the Niigata Prefecture, Japan, conducted in the fall of 2016, we enrolled patients who answered all ASK-12 items and underwent a measured respiratory function test within 1 year. The low-adherence group (ASK-12 ≥ 28) was compared with the control group (ASK-12 < 28), and we conducted a cluster analysis of the low-adherence group.ResultsThere were 170 patients in the low-adherence group and 402 patients in the control group. There was a significant difference between age, gender, working status, smoking history, the percentage of forced expiratory volume in one second (%FEV₁), asthma control test (ACT), and Patient Health Questionnaire-9 (PHQ-9) score between the two groups. Logistic analysis revealed that working status (working), % FEV₁ (<90%), and PHQ-9 score (>5) were independent factors for the low-adherence group. The cluster analysis identified three clusters in the low-adherence group. Among these, one cluster was characterized by elderly males with chronic obstructive pulmonary disease and another by middle-aged nonsmoking females with a depression tendency, had problems with asthma control.ConclusionsSeveral factors were considered to be attributed to low drug-adherence. There were several phenotypes in the low-adherence population correlated with incomplete asthma control. Intervention with drug adherence should be a future goal for asthma treatment.     

The A118G single-nucleotide polymorphism in OPRM1 is a risk factor for asthma severity

BackgroundAlthough population studies have implicated emotional burden in asthma severity, the underlying genetic risk factors are not completely understood. We aimed to evaluate the genetic influence of a functional single-nucleotide polymorphism (SNP) in the stress-related μ-opioid receptor gene (OPRM1; A118G SNP, rs1799971) on asthma severity.MethodsWe initially assessed disease severity in asthmatic outpatients carrying A118G. Using an ovalbumin-induced experimental asthma rodent model harboring the functionally equivalent SNP, we investigated the mechanism by which this SNP influences the allergic immune response.ResultsAmong 292 outpatients, 168 underwent airway hyperresponsiveness (AHR) to methacholine testing. Compared with patients carrying the AA and AG genotypes, those carrying the GG genotype exhibited enhanced AHR. The stress levels were presumed to be moderate among patients and were comparable among genotypes. Compared with Oprm1 AA mice, GG mice demonstrated aggravated asthma-related features and increased pulmonary interleukin-4⁺CD4⁺ effector and effector memory T cells under everyday life stress conditions. Intraperitoneal naloxone methiodide injection reduced effector CD4⁺ T cell elevation associated with increased eosinophil numbers in bronchoalveolar lavage fluid of GG mice to the levels in AA mice, suggesting that elevated Th2 cell generation in the bronchial lymph node (BLN) of GG mice induces enhanced eosinophilic inflammation.ConclusionsWithout forced stress exposure, patients with asthma carrying the OPRM1 GG genotype exhibit enhanced AHR, attributable to enhanced Th2 cell differentiation in the regional lymph node. Further research is necessary to elucidate the role of the OPRM1 A118G genotype in the Th2 cell differentiation pathway in the BLN.     

Triple versus LAMA/LABA combination therapy for Japanese patients with COPD: A systematic review and meta-analysis

BackgroundIn symptomatic COPD patients with a history of exacerbations, additional treatment with inhaled corticosteroid (ICS) to long-acting muscarinic antagonist (LAMA) and long-acting beta-agonist (LABA) combination therapy is recommended based on the evidence of low incidence of exacerbations but with a caution for pneumonia. However, ethnic differences may affect the response to drugs. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of this treatment in the Japanese population (PROSPERO: CRD42020191978).MethodsWe searched relevant randomized control trials and analyzed the exacerbations, quality of life, lung function, and adverse events including pneumonia and mortality as the outcomes of interest.ResultsWe identified a total of three RCTs (N = 632). Treatment with ICS/LAMA/LABA triple therapy significantly decreased the exacerbations (rate ratio, 0.56; 95% CI, 0.38 to 0.85) and improved the trough FEV₁ (mean difference, 0.04; 95% CI, 0.01 to 0.07) compared to LAMA/LABA therapy. However, triple therapy showed a significantly higher incidence of pneumonia compared to LAMA/LABA (odds ratio, 3.38; 95% CI, 1.58 to 7.22). Concerning other adverse events including mortality, there were no significant difference between these therapies.ConclusionsIn the current meta-analysis of the Japanese population, we confirmed that triple therapy causes a higher incidence of pneumonia than LAMA/LABA treatment but is a more preferable treatment since it showed a lower incidence of exacerbations and higher trough FEV₁ in patients with symptomatic moderate to severe COPD. However, since the sample sizes were not statistically large enough, further trials involving Japanese patients are needed.     

Risk factors for progression to acute respiratory failure after casirivimab and imdevimab administration: A retrospective study

BackgroundCasirivimab and imdevimab are effective in preventing hospitalization in outpatients with coronavirus disease 2019 (COVID-19); however, disease progression after casirivimab and imdevimab administration has been reported. This study aimed to elucidate the risk factors for disease progression after casirivimab and imdevimab administration.MethodsThis retrospective study included patients with COVID-19 who received casirivimab and imdevimab at Hiroshima City Funairi Citizens Hospital between August 6, 2021, and October 10, 2021. All patients had at least one risk factor for severe disease and were treated on admission. The patients’ background characteristics and test results at the first visit were analyzed. The patients were divided into two groups (progressed and improved) based on whether they progressed to acute respiratory failure during hospitalization.ResultsSixty-seven patients were included: 9 patients in the progressed group (median age, 56 years) and 58 patients in the improved group (median age, 51 years). Age, coexistence rate of diabetes, cycle threshold value of polymerase chain reaction test, rate of detectable pneumonia on chest radiographs or chest computed tomography images, lymphocyte count, and the levels of C-reactive protein, interleukin-6, glucose, and glycated hemoglobin were significantly different between the two groups. Multivariate logistic regression analysis revealed that the coexistence of diabetes and the presence of detectable pneumonia on chest radiographs were independent factors predicting the progression to acute respiratory failure.ConclusionAcute respiratory failure after antibody therapy with casirivimab and imdevimab may develop in patients with diabetes or detectable pneumonia on chest radiographs at the first visit.     

‘Real-life’ experience in asthmatic children treated with omalizumab up to six-years follow-up

Introduction and objectivesOmalizumab is present in international guidelines for the control of severe asthma, but data on the long-term effects in children are limited. Our objective was to perform a ‘real-life’ long-term trial of omalizumab in children with allergic asthma.Materials and methodsAn observational single center ‘real-life’ study was performed. Data for treatment, lung function, side effect, asthma exacerbations and hospitalizations were recorded at six months and annually.ResultsForty-eight patients <18 years of age were enrolled. Median treatment period was 2.9 (0.5–6). Fluticasone dose for the maintenance treatment decreases significantly at six months (452 mcg/day to 329.89 mcg/day, respectively). This difference was maintained throughout the follow-up. Nobody used oral corticosteroid after six months. The rate of hospital admissions and visits to the emergency department for asthma exacerbations decreased significantly in the third years and fourth years follow-up, respectively. There was an improvement in lung function. Mean values of FEV₁ and FEF_25–75% before treatment were 79.88 and 62.94, respectively; after six months of treatment a statistically significant change was seen with a mean FEV₁ of 92.29 and FEF_25–75% of 76.31 (p = 0.0001). Lung function values were above normal throughout the six years of treatment. No side effects were reported.ConclusionsOverall in ‘real life’ omalizumab in children reduces asthma exacerbations and hospitalizations, improves lung function, and decreases the maintenance therapy. It is shown to be safe for up to six years of treatment in children.     

Prevalence,disease burden,and treatment reality of patients with severe,uncontrolled asthma in Japan

BackgroundThe severe asthma and severe, uncontrolled asthma (SUA) populations in Japan are not well-studied. We investigated the prevalence of continuously treated severe asthma and SUA patients, their disease burden, and the treatment reality via a Japanese health insurance claims database.MethodsContinuously treated asthma patients (patients prescribed inhaled corticosteroids for asthma ≥4 times in the past year) aged ≥17 years at the index date (latest visit between April 2014 and March 2015 for asthma treatment) were included in this analysis (KEIFU study, UMIN000027695). Asthma severity and control status at the index date were defined using modified criteria of ERS/ATS guidelines. Asthma hospitalization, oral corticosteroid (OCS) use, and total medical expenses were calculated using data up to 12 months post–index date.ResultsWe identified 10,579 patients as continuously treated asthma patients. Of these, 823 (7.8%) had severe asthma; 267 (2.5%) and 556 (5.3%) patients had SUA and severe, controlled asthma (SCA), respectively. Compared with SCA and mild to moderate asthma patients, a greater percentage of SUA patients required hospitalization (13.7%, 6.2%, and 3.0%, respectively) and were prescribed OCSs (67.4%, 45.9%, and 16.2%, respectively). Yearly total medical expenses were also greater for SUA patients (mean [standard deviation]: 8346 [12,280], vs 5989 [10,483] and 3422 [8800] USD, respectively).ConclusionsThe percentages of severe asthma and SUA patients continuously treated in Japan were obtained through this large-scale analysis using a health insurance claims database. SUA patients had greater medical and economic burdens, suggesting more appropriate treatment is required according to the treatment guidelines.