Associations of COVID-19 symptoms with omicron subvariants BA.2 and BA.5, host status, and clinical outcomes in Japan: a registry-based observational study.

BACKGROUND: Previous SARS-CoV-2 infection and vaccination, coupled with the rapid evolution of SARS-CoV-2 variants, have modified COVID-19 clinical manifestations. We aimed to characterise the clinical symptoms of COVID-19 individuals in omicron BA.2 and BA.5 Japanese pandemic periods to identify omicron and subvariant associations between symptoms, immune status, and clinical outcomes. METHODS: In this registry-based observational study, individuals registered in Sapporo's web-based COVID-19 information system entered 12 pre-selected symptoms, days since symptom onset, vaccination history, SARS-CoV-2 infection history, and background. Eligibility criteria included symptomatic individuals who tested positive for SARS-CoV-2 (PCR or antigen test), and individuals who were not tested for SARS-CoV-2 but developed new symptoms after a household member tested positive for SARS-CoV-2. Symptom prevalence, variables associated with symptoms, and symptoms associated with progression to severe disease were analysed. FINDINGS: Data were collected and analysed between April 25 and Sept 25, 2022. For 157 861 omicron-infected symptomatic individuals, cough was the most common symptom (99 032 [62·7%] patients), followed by sore throat (95 838 [60·7%] patients), nasal discharge (69 968 [44·3%] patients), and fever (61 218 [38·8%] patients). Omicron BA.5 infection was associated with a higher prevalence of systemic symptoms than BA.2 in vaccinated and unvaccinated individuals (adjusted odds ratio [OR] for fever: 2·18 [95% CI 2·12-2·25]). Omicron breakthrough-infected individuals with three or more vaccinations or previous infection were less likely to exhibit systemic symptoms (fever 0·50 [0·49-0·51]), but more likely to exhibit upper respiratory symptoms (sore throat 1·33 [1·29-1·36]; nasal discharge 1·84 [1·80-1·89]). Infected older individuals (≥65 years) had lower odds for all symptoms. However, when symptoms were manifest, systemic symptoms were associated with increased odds for severe disease (dyspnoea 3·01 [1·84-4·91]; fever 2·93 [1·89-4·52]), whereas upper respiratory symptoms were associated with decreased odds (sore throat 0·38 [0·24-0·63]; nasal discharge 0·48 [0·28-0·81]). INTERPRETATION: Host immunological status, omicron subvariant, and age were associated with a spectrum of COVID-19 symptoms and outcomes. BA.5 produced a higher systemic symptom prevalence than BA.2. Vaccination and previous infection reduced systemic symptom prevalence and improved outcomes but increased upper respiratory tract symptom prevalence. Systemic, but not upper respiratory, symptoms in older people heralded severe disease. Our findings could serve as a practical guide to use COVID-19 symptoms to appropriately modify health-care strategies and predict clinical outcomes for older patients with omicron infections. FUNDING: Japan Agency for Medical Research and Development.

Associations of COVID-19 Symptoms with Omicron Subvariants BA.2 and BA.5, Host Status, and Clinical Outcomes: A Registry-Based Observational Study in Sapporo, Japan.

Background: Previous SARS-CoV-2 infection and vaccination, coupled to rapid evolution of SARS-CoV-2 variants, have modified COVID-19 clinical manifestations. We characterized clinical symptoms of COVID-19 individuals in omicron BA.2 and BA.5 Japanese pandemic periods to identify omicron and subvariant associations between symptoms, immune status, and clinical outcomes. Methods: Individuals registered in Sapporo's web-based COVID-19 information system entered 12 pre-selected symptoms, days since symptom onset, vaccination history, SARS-CoV-2 infection history, and background. Symptom frequencies, variables associated with symptoms, and symptoms associated with progression to severe disease were analysed. Results: For all omicron-infected individuals, cough was the most common symptom (62.7%), followed by sore throat (60.7%), nasal discharge (44.3%), and fever (38.8%). Omicron BA.5 infection was associated with a higher symptom burden than BA.2 in vaccinated and unvaccinated individuals. Omicron breakthrough-infected individuals with ≥ 3 vaccinations or previous infection were less likely to exhibit systemic symptoms, but more likely to exhibit upper respiratory symptoms. Infected elderly individuals had lower odds for all symptoms, but, when symptoms were manifest, systemic symptoms were associated with an increased risk, whereas upper respiratory symptoms with a decreased risk, of severe disease. Conclusion: Host immunological status, omicron subvariant, and age were associated with a spectrum of COVID-19 symptoms and outcomes. BA.5 produced a greater symptom burden than BA.2. Vaccination and prior infection mitigated systemic symptoms and improved outcomes, but increased upper respiratory tract symptom burden. Systemic, but not upper respiratory, symptoms in the elderly heralded severe disease.

C-reactive protein level predicts need for medical intervention in pregnant women with SARS-CoV2 infection: A retrospective study.

AIM: To make effective use of the limited available hospital space during the Coronavirus disease 2019 (COVID-19) pandemic, we conducted this study to investigate the laboratory indices that identify pregnant women with SARS-CoV2 infection who require medical intervention. METHODS: We carried out a retrospective analysis of pregnant women positive for COVID-19 who were admitted to Hokkaido University Hospital from September 2020 to June 2021. Medical interventions included oxygen supplementation, systemic corticosteroids, or supplemental liquids to treat infection-related symptoms. RESULTS: Forty-two infected pregnant patients were admitted to the hospital, half of whom required medical intervention (n = 21). Fever, C-reactive protein (CRP), and platelet count are all associated with need for medical intervention. Of the 32 patients with a fever of ≥37.5°C on days 0-3 after onset of syndromes, 22 (69%) continued to have a fever on days 4-6, of which 19 (86.4%) required medical intervention. CRP level on days 4-6 predicted the presence or absence of medical intervention (area under the receiver operating characteristic curve = 0.913), with a sensitivity of 81% and specificity of 100% at a CRP cutoff of 1.28 mg/dL. CONCLUSIONS: The need for medical intervention in pregnant patients can be predicted with high accuracy using a CRP cutoff of 1.28 mg/dL on days 4-6 after onset of syndromes. The presence of fever also may be an easy marker for selecting subjects who need or will need therapeutic intervention. These could be an effective triage method to determine appropriate indications for the hospitalization of pregnant women in future outbreaks.

Implementation Status of Liver Function Tests for Monitoring Benzbromarone-Induced Hepatotoxicity: An Epidemiological Survey Using the Japanese Claims Database.

A major adverse effect of benzbromarone is hepatotoxicity. Therefore, periodic liver function tests are required at least for the first 6 months of benzbromarone administration. However, it is not clear whether the relevant blood tests are implemented appropriately. Here, we performed a cross-sectional survey of the implementation status of liver function tests in patients who were newly prescribed benzbromarone, using the Japanese large claims database. Male patients who were newly prescribed benzbromarone from January 2010 to December 2016 were included. We targeted patients who continued benzbromarone during the observation period (up to 180 d from the start of administration). The primary endpoint was the proportion of patients in whom periodic liver function tests were implemented. A periodic liver function test was defined as one or more liver function tests performed during both 1-90 and 91-180 d of initial benzbromarone administration. We labeled the tests as a "periodic test" or "non-periodic test" based on whether periodic liver function tests were performed or not, respectively. Furthermore, factors influencing non-periodic test were analyzed. Periodic testing was implemented only in 28.7% of patients. Additionally, factors such as number of hospital beds ≤19 (compared to 100-199 beds) and duration of the first prescription of benzbromarone were associated with non-periodic testing. Our study revealed that periodic liver function tests are not performed sufficiently in Japan. Thus, clinicians prescribing benzbromarone should be educated about the test. Our blood-test-based approach should be applied to other drugs and countries in future research.

Characteristics of COVID-19 patients admitted into two hospitals in sapporo, Japan: Analyses and insights from two outbreak waves.

BACKGROUND: Coronavirus disease (COVID-19) emerged in January 2020 in Sapporo city, and the outbreak has shown two peaks. METHODS: A total of 260 COVID-19 patients were enrolled and categorized into three groups according to the pandemic pattern, jobs and situation, and disease severity. We compared clinical characteristics according to these categories. RESULTS: We found two pandemic peaks, and the proportion of patients and health providers who were infected in other hospitals had increased in the latter two periods (period 2: 49.6%, period 3: 32.7%). Particularly, the proportion of infected health providers was 27% in period 2, and they tended to be younger females with a mild condition. Severity of the disease (requirement of oxygen and/or mechanical ventilation) was associated with advanced age, and all the patients who died during admission were over 60 years old. CONCLUSIONS: We reported the temporal dynamics and characteristics of the COVID-19 pandemic in Sapporo city, Japan. This survey from the viewpoint of the hospital provides a new insight into and a better guide for the further management of the COVID-19 pandemic.

Rapidly progressive organizing pneumonia associated with COVID-19.

We report a case of clinically diagnosed secondary organizing pneumonia (SOP) associated with coronavirus disease 2019 (COVID-19). A 70-year-old woman who had been diagnosed with COVID-19 was admitted to Hokkaido University Hospital. Although her fever, cough, dyspnea, and serum C-reactive protein levels improved, she developed rapidly progressive respiratory failure and computed tomography revealed the development of bilateral lung consolidation. Her dyspnea was relieved, and her oxygenation levels and radiological findings improved after commencing corticosteroid treatment. Blood biomarkers for interstitial lung disease, Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D), showed different responses during the clinical course of her disease. Evaluation of serial changes in levels of KL-6 and SP-D may help diagnose and monitor COVID-19-associated organizing pneumonia (OP). Clinicians should be aware that SOP can develop in response to COVID-19 and that these patients may benefit from the use of steroids.

Proposal of COVID-19 Clinical Risk Score for the management of suspected COVID-19 cases: a case control study.

BACKGROUND: No clinical scoring system has yet been established to estimate the likelihood of coronavirus disease (COVID-19) and determine the suitability of diagnostic testing in suspected COVID-19 patients. METHODS: This was a single-center, retrospective, observational study of patients with suspected COVID-19 and confirmed COVID-19. Patient background, clinical course, laboratory and computed tomography (CT) findings, and the presence of alternative diagnoses were evaluated. Clinical risk scores were developed based on clinical differences between patients with and without COVID-19. RESULTS: Among 110 patients suspected of having COVID-19, 60.9% underwent polymerase chain reaction (PCR) testing based on the judgment of physicians. Two patients were found to have COVID-19. The clinical characteristics of 108 non-COVID-19 patients were compared with those of 23 confirmed COVID-19 patients. Patients with COVID-19 were more likely to have a history of high-risk exposures and an abnormal sense of taste and smell. The COVID-19 group had significantly higher rates of subnormal white blood cell counts, lower eosinophil counts, and lower procalcitonin levels than the non-COVID-19 group. When blood test results, CT findings, and the presence of alternative diagnoses were scored on an 11-point scale (i.e., "COVID-19 Clinical Risk Score"), the COVID-19 group scored significantly higher than the non-COVID-19 group, more than four points in the COVID-19 group. All non-COVID patients who did not undergo PCR had a score of 4 or less. CONCLUSIONS: The COVID-19 Clinical Risk Score may enable the risk classification of patients suspected of having COVID-19 and can help in decision-making in clinical practice, including appropriateness of diagnostic testing. Further studies and prospective validation with an increased sample size are required.

Unique Mortality Profile in Japanese Patients with COPD: An Analysis from the Hokkaido COPD Cohort Study.

Purpose: Causes of death may be unique and different in Japanese patients with COPD because they are generally older, thinner, experience fewer exacerbations, and live longer than those in other countries. We investigated the detailed mortality profile in the Hokkaido COPD cohort study, which completed a 10-year follow-up with a very low dropout rate. Patients and Methods: We prospectively examined the 10-year natural history in 279 Japanese patients with COPD (GOLD 1, 26%; GOLD 2, 45%; GOLD 3, 24%; and GOLD 4, 5%). The majority of patients were male, and the average age at baseline was 69 years old. About 95% of all patients had accurate mortality data. The risk factors for mortality were also analyzed. Results: During the 10 years, 112 patients (40%) died. Their median survival time was 6.1 years (interquartile range: 4.7-7.9 years), and age at death was 79 ± 6 years old (mean ± SD). Respiratory diseases, including pneumonia, were the leading causes of death in 45 (40%), followed by lung cancer in 24 (21%), other cancers in 18 (16%), and cardiovascular diseases in 12 (11%). In particular, lung cancer-related death was equally distributed across all COPD stages, with a higher proportion of lung cancer in the relatively younger generation (<64 years old). Older age at baseline, lower BMI, and severer emphysema were significant risk factors for all-cause mortality. Conclusion: The unique mortality profile observed in this study should be considered when designing strategies for the management of patients with COPD in any geographic region.

Analysis of the Implementation of Blood Tests Specified in the Package Insert After Prescription of Thiamazole.

OBJECTIVES: The antithyroid drug thiamazole has long been known to cause the serious adverse effect of agranulocytosis, and performing regular blood tests is listed among the warnings on the package insert. We conducted a retrospective survey of how often doctors conducted blood tests in accordance with the package insert when thiamazole was prescribed at our hospital. METHODS: The subjects were patients to whom thiamazole was newly prescribed at our hospital between April 2004 and March 2012. During the target period, thiamazole was newly prescribed to 438 patients. RESULTS: We found that blood tests after prescription of thiamazole as listed in the warning section on the package insert are not performed sufficiently. The rate at which white blood cell counts were obtained decreased over time. The rate at which differential leukocyte counts were obtained was approximately 80% of white blood cell counts at all observational time points. In contrast, the percentage of subjects whose white blood cell counts were measured increased according to a time-trend analysis. CONCLUSIONS: This study revealed that blood tests after prescription of thiamazole as listed in the warning section on the package insert are not performed sufficiently at our hospital. The rate at which differential leukocyte counts were obtained was approximately 80% of white blood cell counts at all observational periods. Physician education should be more rigorously performed than presently done, and automatic generation of warnings that urge blood tests and patient education regarding the importance of blood tests is also important.

Annual change in FEV1 in elderly 10-year survivors with established chronic obstructive pulmonary disease.

Long-term decline in lung function is generally considered to be progressive in individuals with established chronic obstructive pulmonary disease (COPD), despite the presence of intersubject variation. We hypothesized that the annualized rate of decline in forced expiratory volume in 1 second (FEV1) would not be constant among different time periods in the natural history of established COPD. We compared the annual change rates in FEV1 during the first 5 years and the last 5 years, estimated separately using a linear mixed-effects model in 10-year survivors (n = 110). The subjects were classified into three FEV1 decline groups, based on the 25th and 75th percentile values in each time period. The rates of FEV1 changes, calculated from the first 5 years and the last 5 years, did not correlate with each other among 10-year survivors; the subjects of each FEV1 decline group during the first 5 years did not consistently remain in the same FEV1 decline group during the last 5 years. Smoking status and exacerbation frequency were not associated with decline in FEV1. In conclusion, the disease activity, which is often expressed as annualized change in FEV1, might be changeable either way over years in patients with established COPD.

Characteristics of Medical Adverse Events/Near Misses Associated With Laparoscopic/Thoracoscopic Surgery: A Retrospective Study Based on the Japanese National Database of Medical Adverse Events.

OBJECTIVES: The aim of this study was to clarify the characteristics of adverse events/near misses during laparoscopic/thoracoscopic surgery. METHODS: Using relevant key words for minimally invasive surgeries, 540 records were identified in the database of the Japan Council for Quality Health Care. After data review and the classification of adverse events, 746 events associated with laparoscopic (laparo group) and/or thoracoscopic (thoraco group) surgery were identified. We calculated the frequency of each event, compared the frequency regarding recurrent events, and evaluated the types of event that had resulted in deaths between the 2 groups. RESULTS: There were 582 events in the laparo group, 159 in the thoraco group, and 5 in those undergoing combined surgery. Overall, injury of other organs (11.4%, 85/746), retention of a foreign body (9.1%, 68/746), breakage/failure of medical equipment or devices (6.2%, 46/746), massive bleeding (5.9%, 44/746), misperception of anatomy (5.6%, 42/746), and vascular injury (4.8%, 36/746) were frequently reported. There were marked differences in the frequency of injury of other organs (laparo group: 13.4%, 78/582; thoraco group: 4.4%, 7/159), massive bleeding (laparo group: 3.4%, 20/582; thoraco group: 14.5%, 23/159), and vascular injury (laparo group: 2.6%, 15/582; thoraco group: 12.6%, 20/159) between the 2 groups. Among the 56 patient-death reports, 132 adverse events were identified. In the thoraco group, bleeding events were frequently observed, whereas in the laparo group, various categories of events were noted. CONCLUSIONS: We observed recurrent incidents and differences in the frequency between the 2 groups. Surgeons should keep in mind these characteristics. Retention of a foreign body and the breakage/malfunctioning of instruments might be reduced by the introduction of specialized checklists.

Venipuncture Nerve Injuries in the Upper Extremity From More Than 1 Million Procedures.

OBJECTIVES: The purpose of this study was to investigate the nerve injury rate for 1 million venipunctures and the efficacy of attempts to avoid severe nerve injury. METHODS: We collected data for outpatients from whom a venipuncture blood sample was obtained in our hospital from 2005 to 2014. Every venipuncture procedure for outpatients was performed by a trained nurse or clinical technologist at the center for blood sampling in our hospital. In addition, a series of lectures by a specialist is held in our hospital at various times. All complaints related to venipuncture blood sampling were reported to our division of hospital safety management and were followed up using the guidelines for injuries related to the venipuncture. RESULTS: The number of venipuncture-related complications was 293 (0.027%, 1/3700) of 1,082,053 during the 10 years. A total of 40 of the 1,082,053 venipunctures were referred to the department of orthopedic surgery, and 16 (0.0015%, 1/67,000) were diagnosed with obvious nerve injuries. The average duration of the treatment was 46.4 days (range, 1-126 days); 69% of the patients recovered within 5 weeks, and all patients recovered within 18 weeks. CONCLUSIONS: Although it is impossible to completely prevent venipuncture-related complications, appropriate venipuncture skills and risk management decrease the incidence of chronic or permanent nerve injury risk after venipuncture.

A Semiquantitative Computed Tomographic Grading System for Evaluating Therapeutic Response in Pulmonary Alveolar Proteinosis.

RATIONALE: A useful semiquantitative method of using computed tomographic (CT) images to evaluate therapeutic response in pulmonary alveolar proteinosis (PAP) has not been established, although the extent score or grading score of ground-glass opacities has been used. OBJECTIVES: The purpose of this study was to establish a semiquantitative method for evaluating therapeutic response in PAP. METHODS: CT scans were obtained within 1 month before and after therapy from 32 patients with PAP who participated in a multicenter phase II trial of granulocyte-macrophage colony-stimulating factor inhalation therapy. The scans were evaluated by two chest radiologists independently. Increased parenchymal opacity was evaluated on the basis of its intensity and extent (CT grade), and the severity scores were compared with CT scores based on the extent alone (CT extent), as well as on the basis of physiological and serological results. RESULTS: CT grade score and CT extent score had significant correlation with diffusing capacity of the lung for carbon monoxide percent predicted (%DlCO), PaO2, VC percent predicted (%VC), Krebs von den Lungen (KL)-6, and surfactant protein D. The change in CT grade score between pre- and post-treatment examinations (ΔCT grade) correlated better with difference of PaO2 between pre- and post-treatment examinations (ΔPaO2) than ΔCT extent (difference of CT extent score between pre- and post-treatment examinations). In univariate analysis, ΔCT grade, ΔCT extent, ΔKL-6, Δ%DlCO, Δ%VC, and change in surfactant protein D correlated significantly with ΔPaO2. In multivariate analysis, ΔCT grade and ΔKL-6 correlated more closely with ΔPaO2. CONCLUSIONS: Although a number of CT variables were collected, the currently proposed grading system that correlates well with PaO2 should be viewed as a retrospective scoring system that needs future validation with another PAP cohort.

Physicians' responses to computerized drug interaction alerts with password overrides.

BACKGROUND: Although evidence has suggested that computerized drug-drug interaction alert systems may reduce the occurrence of drug-drug interactions, the numerous reminders and alerts generated by such systems could represent an excessive burden for clinicians, resulting in a high override rate of not only unimportant, but also important alerts. METHODS: We analyzed physicians' responses to alerts of relative contraindications and contraindications for coadministration in a computerized drug-drug interaction alert system at Hokkaido University Hospital. In this system, the physician must enter a password to override an alert and continue an order. All of the drug-drug interaction alerts generated between December 2011 and November 2012 at Hokkaido University Hospital were included in this study. RESULTS: The system generated a total of 170 alerts of relative contraindications and contraindication for coadministration; 59 (34.7 %) of the corresponding orders were cancelled after the alert was accepted, and 111 (65.3 %) were overridden. The most frequent contraindication alert was for the combination of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors and fibrates. No incidents involving drug-drug interactions were reported among patients who were prescribed contraindicated drug pairs after an override. CONCLUSIONS: Although computerized drug-drug interaction alert systems that require password overrides appear useful for promoting medication safety, having to enter passwords to override alerts may represent an excessive burden for the prescribing physician. Therefore, both patient safety and physicians' workloads should be taken into consideration in future designs of computerized drug-drug interaction alert systems.

Time trend of injection drug errors before and after implementation of bar-code verification system.

BACKGROUND: Bar-code technology, used for verification of patients and their medication, could prevent medication errors in clinical practice. OBJECTIVE: Retrospective analysis of electronically stored medical error reports was conducted in a university hospital. METHODS: The number of reported medication errors of injected drugs, including wrong drug administration and administration to the wrong patient, was compared before and after implementation of the bar-code verification system for inpatient care. RESULTS: A total of 2867 error reports associated with injection drugs were extracted. Wrong patient errors decreased significantly after implementation of the bar-code verification system (17.4/year vs. 4.5/year, p< 0.05), although wrong drug errors did not decrease sufficiently (24.2/year vs. 20.3/year). The source of medication errors due to wrong drugs was drug preparation in hospital wards. CONCLUSION: Bar-code medication administration is effective for prevention of wrong patient errors. However, ordinary bar-code verification systems are limited in their ability to prevent incorrect drug preparation in hospital wards.

Duration of benefit in patients with autoimmune pulmonary alveolar proteinosis after inhaled granulocyte-macrophage colony-stimulating factor therapy.

BACKGROUND: Treatment of autoimmune pulmonary alveolar proteinosis (aPAP) by subcutaneous injection or inhaled therapy of granulocyte-macrophage colony-stimulating factor (GM-CSF) has been demonstrated to be safe and efficacious in several reports. However, some reports of subcutaneous injection described transient benefit in most instances. The durability of response to inhaled GM-CSF therapy is not well characterized. METHODS: To elucidate the risk factors for recurrence of aPAP after GM-CSF inhalation, 35 patients were followed up, monitoring for the use of any additional PAP therapies and disease severity score every 6 months. Physiologic, serologic, and radiologic features of the patients were analyzed for the findings of 30-month observation after the end of inhalation therapy. RESULTS: During the observation, 23 patients remained free from additional treatments, and twelve patients required additional treatments. There were no significant differences in age, sex, symptoms, oxygenation indexes, or anti-GM-CSF antibody levels at the beginning of treatment between the two groups. Baseline vital capacity (% predicted, %VC) were higher among those who required additional treatment (P<.01). Those patients not requiring additional treatment maintained the improved disease severity score initially achieved. A significant difference in the time to additional treatment between the high %VC group (%VC≥80.5) and the low %VC group was seen by a Kaplan-Meier analysis and a log-rank test (P<.0005). CONCLUSIONS: These results demonstrate that inhaled GM-CSF therapy sustained remission of aPAP in more than one-half of cases, and baseline %VC might be a prognostic factor for disease recurrence. TRIAL REGISTRY: ISRCTN Register and JMACCT Clinical Trial Registry; No.: ISRCTN18931678 and JMAIIA00013; URL: http://www.isrctn.org and http://www.jmacct.med.or.jp.

Serum KL-6 concentrations are associated with molecular sizes and efflux behavior of KL-6/MUC1 in healthy subjects.

BACKGROUND: Serum KL-6, a sialylated sugar chain on human MUC1, is used as a marker of interstitial lung diseases. We recently reported that efflux behavior of KL-6/MUC1 from the alveoli into the bloodstream assessed by molecular analysis differed according to genetically determined molecular sizes and influenced serum KL-6 concentrations in sarcoidosis. This study was designed to investigate associations between molecular size and efflux behavior of KL-6/MUC1, and factors contributing to serum KL-6 concentrations in healthy subjects. METHODS: Western blot analysis using anti-KL-6 antibody was performed on serum obtained from 250 healthy subjects. RESULTS: The efflux behavior of KL-6/MUC1 differed according to the genetically determined molecular sizes in healthy subjects. In subjects having low molecular size, there were significant associations between smoking status, aging, renal function and serum KL-6 concentrations. However, these associations were not significant in the subjects having higher molecular size and the efflux behavior of high molecular size was the only significant determinant of serum KL-6 concentrations. CONCLUSIONS: This study showed an association between KL-6/MUC1 efflux based on molecular size and serum KL-6 concentrations in healthy subjects. We propose that the molecular size and efflux behavior of KL-6/MUC1 should be considered when interpreting serum KL-6 concentrations.

Impact of asthmatic control status on serum cystatin C concentrations.

BACKGROUND: To determine whether cystatin C accurately reflects renal function in asthma, we investigated serum cystatin C concentrations in a large number of asthmatic patients by adjusting for several confounding factors that might affect serum cystatin C concentrations. METHODS: A total of 126 asthmatic patients and 126 healthy volunteers, matched for age and gender, were studied. RESULTS: Serum cystatin C concentrations in symptomatic subjects with asthma were significantly higher than in healthy controls (p < 0.001) and asymptomatic subjects with asthma (p = 0.007), whereas no significant difference was observed between healthy controls and asymptomatic subjects. In asthmatic subjects, serum cystatin C concentrations were not influenced by inhaled corticosteroid (ICS). However, serum cystatin C concentrations were significantly higher in subjects who were regularly treated by oral corticosteroid (OCS) (p = 0.001). CONCLUSIONS: Serum cystatin C concentrations are elevated in asthmatic patients; particularly while symptomatic and/or taking OCS but not ICS. Serum cystatin C concentrations may not accurately reflect renal function in those patients.