Comparison of ceftriaxone plus macrolide and ampicillin/sulbactam plus macrolide in treatment for patients with community-acquired pneumonia without risk factors for aspiration: an open-label, quasi-randomized, controlled trial.

BACKGROUND: Ceftriaxone (CTRX) and ampicillin/sulbactam (ABPC/SBT) are recommended by various guidelines as the first-line antibiotics for community-acquired pneumonia (CAP). However, which of these antibiotics is more effective for treating non-aspiration CAP remains unclear. METHODS: This study was a prospective, single-center, open-label, quasi-randomized controlled trial. Patients with adult CAP without risk for aspiration were allocated to either a CTRX or ABPC/SBT group based on the date of hospital admission. Macrolide was added to patients in each group. The primary outcome was the clinical response in the validated per-protocol (VPP) population at end of treatment (EOT). The secondary outcomes were clinical response during treatment and at end of study (EOS) in the VPP population, and mortality rate at day 30 in the modified intention-to-treat (MITT) population. RESULTS: Of 696 screened patients, 433 patients were excluded and 263 patients were allocated to receive either of the treatments. Males comprised 54% of patients and mean age and PSI were 62.1 ± 19.8 years and 69.3 ± 30.0, respectively, with 124 patients allocated to the CTRX group and 138 patients allocated to the ABPC/SBT group. The clinical effectiveness rate for the VPP population at EOT was 90% in the CTRX and 96% in the ABPC/SBT group (p = 0.072, 95% confidence interval [CI] of risk difference [RD]: - 12.6-0.8%). No significant difference in effectiveness at day 4 was observed between the CTRX and ABPC/SBT groups (p = 0.079, 95%CI of RD: - 12.1-0.4%), but at day 7, ABPC/SBT was significantly more effective than CTRX in the VPP population (p = 0.047, 95%CI of RD: - 13.3--0.4%). No significant difference in late response at EOS was seen between CTRX and ABPC/SBT groups: cure (89 [86%] and 102 [94%]), relapse (5 [5%] and 1 [1%]) and failure (10 [10%] and 5 [5%]; p = 0.053). Deaths within 30 days in MITT population was higher in CTRX group (4 [3%]) than in ABPC/SBT group (0 [0%]) (p = 0.048, 95%CI of RD: 0.1-6.3%). CONCLUSION: No significant difference in effectiveness was found between ABPC/SBT and CTRX at EOT. However, ABPC/SBT might be more effective in the early phase of treatment. TRIAL REGISTRATION: UMIN-CTR, UMIN000037464. Registered 25 July 2019 - Retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042262.

Efficacy of corticosteroid therapy for oxygen-free coronavirus disease 2019-derived pneumonia.

Corticosteroid therapy for oxygen-free coronavirus disease 2019 (COVID-19) is not recommended due to its negative prognostic impact, but the efficacy of corticosteroids when limited to COVID-19 pneumonia is unclear. We aimed to evaluate the efficacy of corticosteroid monotherapy for patients with COVID-19 pneumonia without supplemental oxygen. We retrospectively reviewed patients with oxygen-free COVID-19 pneumonia at our institute between September 2020 and August 2021 and assessed the use of corticosteroids and the timing of initiation. We classified the patients into the following 2 groups: those who were initiated corticosteroids without developing respiratory failure (early steroid group) and those who were not (standard of care [SOC] group). We used inverse probability of treatment weighting (IPW) to balance between the groups. The primary outcome was the incidence of respiratory failure. A total of 144 patient records were reviewed; 63 patients were in the early steroid group and 81 patients were in the SOC group. Of all patients, 14 (22.2%) and 27 (33.3%) patients in the early steroid and SOC group, respectively, required supplemental oxygen (P = .192). After adjusted by the IPW method, 10 (16.0%) and 32 (40.1%) patients in the early steroid and SOC groups, respectively, required supplemental oxygen (P = .004). The logistic regression analysis indicated that early corticosteroid use was significantly associated with a decreased incidence of respiratory failure (odds ratio; 0.17, 95% confidence intervals; 0.06-0.46, P < .001). Corticosteroid monotherapy may suppress the development of exacerbation requiring oxygen supply in patients with oxygen-free COVID-19 pneumonia.

[A case of miliary tuberculosis complicated by a tuberculous aneurysm of the thoracic aorta].

An 85-year-old woman was admitted to our hospital with the chief complaint of fever. Antibiotics were not effective and a chest computed tomography scan revealed a diffuse micronodular shadow and thoracic aortic aneurysm. Subsequently, a bronchoscopy sputum culture was positive for Mycobacterium tuberculosis. Two months after the initiation of chemotherapy, the thoracic aortic aneurysm enlarged despite the improvement in lung findings. Tuberculous aneurysms are quite rare, but can be critical and acute. Therefore, caution should be exercised when treating such patients.

Analysis of longitudinal changes in dyspnea of patients with chronic obstructive pulmonary disease: an observational study.

BACKGROUND: Guidelines recommend that symptoms as well as lung function should be monitored for the management of patients with chronic obstructive pulmonary disease (COPD). However, limited data are available regarding the longitudinal change in dyspnea, and it remains unknown which of relevant measurements might be used for following dyspnea. METHODS: We previously consecutively recruited 137 male outpatients with moderate to very severe COPD, and followed them every 6 months for 5 years. We then reviewed and reanalyzed the data focusing on the relationships between the change in dyspnea and the changes in other clinical measurements of lung function, exercise tolerance tests and psychological status. Dyspnea with activities of daily living was assessed with the Oxygen Cost Diagram (OCD) and modified Medical Research Council dyspnea scale (mMRC), and two dimensions of disease-specific health status questionnaires of the Chronic Respiratory Disease Questionnaire (CRQ) and the St. George's Respiratory Questionnaire (SGRQ) were also used. Dyspnea at the end of exercise tolerance tests was measured using the Borg scale. RESULTS: The mMRC, CRQ dyspnea and SGRQ activity significantly worsened over time (p < 0.001), but the OCD did not (p = 0.097). Multiple regression analyses revealed that the changes in the OCD, mMRC, CRQ dyspnea and SGRQ activity were significantly correlated to changes in forced expiratory volume in one second (FEV1) (correlation of determination (r²) = 0.05-0.19), diffusing capacity for carbon monoxide (r² = 0.04-0.08) and psychological status evaluated by Hospital Anxiety and Depression Scale (r² = 0.14-0.17), although these correlations were weak. Peak Borg score decreased rather significantly, but was unrelated to changes in clinical measurements. CONCLUSION: Dyspnea worsened over time in patients with COPD. However, as different dyspnea measurements showed different evaluative characteristics, it is important to follow dyspnea using appropriate measurements. Progressive dyspnea was related not only to progressive airflow limitation, but also to various factors such as worsening of diffusing capacity or psychological status. Changes in peak dyspnea at the end of exercise may evaluate different aspects from other dyspnea measurements.

[A case of pyogenic spondylitis mimicking spinal invasion of lung cancer].

A 65-year-old man who had suffered from traumatic spinal cord injury had chronic lumbar pain. He had exacerbation of lumbar pain and intermittent fever and consulted several doctors, but the cause of the lumbar pain was unknown. An orthopedic specialist took an MRI. Spinal MRI showed increased signal intensity at the level of T10-11 and a mass in his right lower lung field, so he was referred to our hospital. Two transbronchial lung biopsy procedures failed to obtain malignant cells. CT guided biopsy showed fibrous and hyalinizing tissue contained plasma cells and lyphocytes. Staphylococcus aureus was cultured from the second bronchial lavage fluids of brush and blood cultures, so we began administration of ampicillin-sulbactam. Avoiding threatened or actual cord compression due to collapse resulting from spinal instability, posterior fusion with instrumentation was done through the back of his chest wall. At once, bone biopsy was done, and showed no malignant cells. As soon as antibacterial treatment was stopped after the operation, he had bloody sputa and fever. The antibacterial agent was resumed and the symptoms improved. The mass decreased in size and lumbar pain improved gradually, so we concluded the diagnosis was pyogenic spondylitis caused by S. aureus. After about 5 months of antibacterial treatment, the tumor substantially diminished.

Tazobactam/piperacillin for moderate-to-severe pneumonia in patients with risk for aspiration: comparison with imipenem/cilastatin.

BACKGROUND: Treatment of aspiration pneumonia is becoming an important issue due to aging of populations worldwide. Effectiveness of tazobactam/piperacillin (TAZ/PIPC) in aspiration pneumonia is not clear. PURPOSE: To compare clinical efficacy between TAZ/PIPC (1:4 compound) and imipenem/cilastatin (IPM/CS) in patients with moderate-to-severe aspiration pneumonia. PATIENTS AND METHODS: In this open-label, randomized study either TAZ/PIPC 5 g or IPM/CS 1 g was intravenously administered every 12 h to patients with moderate-to-severe community-acquired aspiration pneumonia or nursing home-acquired pneumonia with risk for aspiration pneumonia for average 11 days. The primary outcome was clinical response rate at the end of treatment (EOT) in validated per-protocol (VPP) population. Secondary outcomes were clinical response during treatment (days 4 and 7) and at the end of study (EOS) in VPP population, and survival at day 30 in modified intention-to-treat (MITT) population. RESULTS: There was no difference between the groups in primary or secondary outcome. However, significantly faster improvement as measured by axillary temperature (p < 0.05) and WBC count (p = 0.01) was observed under TAZ/PIPC treatment. In patients with gram-positive bacterial infection, TAZ/PIPC was more effective at EOT in VPP population (p = 0.03). CONCLUSION: TAZ/PIPC is as effective and safe as IPM/CS in the treatment of moderate- to-severe aspiration pneumonia.

Multidimensional analyses of long-term clinical courses of asthma and chronic obstructive pulmonary disease.

Asthma and chronic obstructive pulmonary disease (COPD) are chronic respiratory disorders involving obstructive airway defects. There have been many discussions on their similarities and differences. Although airflow limitation expressed as forced expiratory volume in one second (FEV(1)) has been considered to be the main diagnostic assessment in both diseases, it does not reflect the functional impairment imparted to the patients by these diseases. Therefore, multidimensional approaches using multiple measurements in assessing disease control or severity have been recommended, and multiple endpoints in addition to FEV(1) have been set recently in clinical trials so as not to miss the overall effects. In particular, as improving symptoms and health status as well as pulmonary function are important goals in the management of asthma and COPD, some patient-reported measurements such as health-related quality of life or dyspnea should be included. Nonetheless, there have been few reviews on the long-term clinical course comparing asthma and COPD as predicted by measurements other than airflow limitation. Here, we therefore analyzed and compared longitudinal changes in both physiological measurements and patient-reported measurements in asthma and COPD. Although both diseases showed similar long-term progressive airflow limitation similarly despite guideline-based therapies, disease progression was different in asthma and COPD. In asthma, patient-reported assessments of health status, disability and psychological status remained clinically stable over time, in contrast to the significant deterioration of these parameters in COPD. Thus, because a single measurement of airflow limitation is insufficient to monitor these diseases, multidimensional analyses are important not only for disease control but also for understanding disease progression in asthma and COPD.

Effect of exacerbations on health status in subjects with chronic obstructive pulmonary disease.

BACKGROUND: Acute exacerbations may cause deteriorations in the health status of subjects with chronic obstructive pulmonary disease (COPD). The present study prospectively evaluated the effects of such exacerbations on the health status and pulmonary function of subjects with COPD over a 6-month period, and examined whether those subjects showed a steeper decline in their health status versus those subjects without exacerbations. METHODS: A total of 156 subjects with COPD (mean age 71.4 +/- 6.3 years) were included in the analysis. At baseline and after 6 months, their pulmonary function and health status were evaluated using the Chronic Respiratory Disease Questionnaire (CRQ) and the St. George's Respiratory Questionnaire (SGRQ). An acute exacerbation was defined as a worsening of respiratory symptoms requiring the administration of systemic corticosteroids or antibiotics, or both. RESULTS: Forty-eight subjects experienced one or more exacerbations during the 6-month study period, and showed a statistically and clinically significant decline in Symptom scores on the SGRQ, whereas subjects without exacerbations did not show a clinically significant decline. Logistic multiple regression analyses confirmed that the exacerbations significantly influenced the Fatigue and Mastery domains of the CRQ, and the Symptoms in the SGRQ. Twelve subjects with frequent exacerbations demonstrated a more apparent decline in health status. CONCLUSION: Although pulmonary function did not significantly decline during the 6-month period, acute exacerbations were responsible for a decline in health status. To minimize deteriorations in health status, one must prevent recurrent acute exacerbations and reduce the exacerbation frequencies in COPD subjects.

Comparison of health-related quality of life measurements using a single value in patients with asthma and chronic obstructive pulmonary disease.

Three methods have been developed to measure health-related quality of life (HRQoL) expressed as a single value: the global rating scale, the total score obtained from disease-specific instruments, and the preference-based utility index. We compared these different single HRQoL measurements in patients with asthma and chronic obstructive pulmonary disease (COPD). We recruited 167 patients with asthma and 161 patients with COPD. The global rating HRQoL was assessed by the Hyland scale. The total HRQoL was assessed by the Living With Asthma Questionnaire in asthma and the St. George's Respiratory Questionnaire in COPD. The Quality of Well-being (QWB) scale was used for the utility measurement derived from the Medical Outcome Study Short-form 36. The inter-relationships between these three HRQoL values were weak to moderate in asthma and moderate in COPD. In asthma, the Hyland scale was weakly correlated with the total HRQoL (Spearman's rank correlation coefficients [Rs] = -0.20) and moderately with the QWB score (Rs = -0.43). In the stepwise multiple regression analyses, anxiety on the Hospital Anxiety and Depression scale and the dyspnea score tended to correlate more significantly with the single HRQoL values in both asthma and COPD than physiological measurements such as the forced expiratory volume in one second. The Hyland scale was less correlated with existing parameters (cumulative coefficient determination [R(2)] = 0.04) than the total HRQoL (cumulative R(2) = 0.47) and the QWB scale (cumulative R(2) = 0.49) in asthma. The single HRQoL values from the Hyland scale, the total HRQoL and the QWB scale evaluated different aspects of asthma and COPD. The psychological status and dyspnea contributed more significantly to the single HRQoL values in these two disorders than the physiological measurements. In asthma, the Hyland scale was especially different from the other single HRQoL scales and should be evaluated separately from the multi-item HRQoL assessments.

Analysis of longitudinal changes in the psychological status of patients with asthma.

Significant relationships between the psychological status and poor asthma outcomes are often reported. However, most of these studies are cross-sectional and none have evaluated how the psychological status progresses over time during the management of asthma patients. Therefore, we examined the longitudinal changes in the psychological status of asthma patients, and compared them with changes in other clinical measurements. Eighty-seven outpatients with stable asthma after 6 months of treatment were enrolled in this study. The psychological status was evaluated using the Hospital Anxiety and Depression Scale (HADS), the health status using the Asthma Quality of Life Questionnaire (AQLQ) and the St. George's Respiratory Questionnaire (SGRQ). The patient's pulmonary function, peak expiratory flow values and airway hyperresponsiveness were measured at entry and every year thereafter over a 5-year period. Using mixed effects models to estimate the slopes, the HADS anxiety and depression scores did not change significantly over time (p=0.71 and 0.72, respectively). The changes in the HADS scores correlated noticeably with changes in the AQLQ and SGRQ scores, but not with changes in the physiological measurements. The baseline HADS anxiety and depression scores were significantly correlated to the subsequent annual changes in each measurement. The psychological status remained clinically stable over the 5-year study period in patients with stable asthma. Changes in the psychological status were significantly correlated to changes in the health status. The baseline HADS scores were a useful indicator in detecting patients who would show subsequent deterioration in their psychological status.

Longitudinal deteriorations in patient reported outcomes in patients with COPD.

Goals of effective management of patients with chronic obstructive pulmonary disease (COPD) include relieving their symptoms and improving their health status. We examined how such patient reported outcomes would change longitudinally in comparison to physiological outcomes in COPD. One hundred thirty-seven male outpatients with stable COPD were recruited for the study. The subjects health status was evaluated using the St. George's Respiratory Questionnaire (SGRQ) and the Chronic Respiratory Disease Questionnaire (CRQ). Their dyspnoea using the modified Medical Research Council (MRC) scale and their psychological status using the Hospital Anxiety and Depression Scale (HADS) were assessed upon entry and every 6 months thereafter over a 5-year period. Pulmonary function and exercise capacity as evaluated by peak oxygen uptake (VO2) on progressive cycle ergometry were also followed over the same time. Using mixed effects models to estimate the slopes for the changes, scores on the SGRQ, the CRQ, the MRC and the HADS worsened in a statistically significant manner over time. However, changes only weakly correlated with changes in forced expiratory volume in 1s (FEV(1)) and peak (VO2). We demonstrated that although changes in pulmonary function and exercise capacity are well known in patients with COPD, patient reported outcomes such as health status, dyspnoea and psychological status also deteriorated significantly over time. In addition, deteriorations in patient reported outcomes only weakly correlated to changes in physiological indices. To capture the overall deterioration of COPD from the subjective viewpoints of the patients, patient reported outcomes should be followed separately from physiological outcomes.

Dyspnoea with activities of daily living versus peak dyspnoea during exercise in male patients with COPD.

Dyspnoea measurements in chronic obstructive pulmonary disease (COPD) can be broadly divided into two categories: those that assess breathlessness during exercise, and those that assess breathlessness during daily activities. We investigated the relationships between dyspnoea at the end of exercise and during daily activities with clinical measurements and mortality in COPD patients. We examined 143 male outpatients with moderate to very severe COPD. The peak Borg score at the end of progressive cycle ergometry was used for the assessment of peak dyspnoea rating during exercise, and the Baseline Dyspnea Index (BDI) score was used for dyspnoea with activities of daily living. Relationships between these dyspnoea ratings with other clinical measurements of pulmonary function, exercise indices, health status and psychological status were then investigated. In addition, their relationship with the 5-year mortality of COPD patients was also analyzed to examine their predictive ability. Although the BDI score was significantly correlated with airflow limitation, diffusing capacity, exercise indices, health status and psychological status, the Borg score at the end of exercise had non-existent or only weak correlations with them. The BDI score was strongly significantly correlated with mortality, whereas the Borg score was not. Dyspnoea during daily activities was more significantly correlated with objective and subjective measurements of COPD than dyspnoea at the end of exercise. In addition, the former was more predictive of mortality. Dyspnoea with activities of daily living is considered to be a better measurement for evaluating the disease severity of COPD than peak dyspnoea during exercise.

Periodic synchronous discharge occurred in an elderly with acute valacyclovir-associated encephalopathy.

An 81-year-old woman suffering from sarcoidosis, chronic renal failure caused by hypertention was treated by valacyclovir 500 mg/day, for the diagnosis of herpes zoster of her right back. Her consciousness gradually became worse, and 3 days after taking the drug, she was sent to the emergency department of the hospital. Her conscious level was E2V2M5 (Glasgow Coma Scale) and myoclonus especially in her lower extremities occurred. Head CT and MRI show no obvious, acute abnormal findings other than chronic ischemic lesions, while an electroencephalogram (EEG) shows periodic synchronous discharges (PSDs) and disorganized background activity. Based on these findings, she was diagnosed as valacyclovir-associated acute encephalopathy. After conservative therapy of maintenance hemodialysis, her consciousness gradually improved, and PSDs disappeared accordingly and background activity of EEG became improved. In this case report, we presented valacyclovir-associated neurotoxicity with PSDs in EEG as potentially a surrogate marker. We should be cautious to use valaciclovir which may cause drug-induced encephalopathy especially in elderly or patients with renal failure even though the dose was adjusted in advance.

Longitudinal changes in patient vs. physician-based outcome measures did not significantly correlate in asthma.

BACKGROUND AND OBJECTIVE: Although improving health status is one important aim in managing asthmatic patients, few studies have evaluated their health status longitudinally. Therefore, we examined longitudinal changes in health status of asthma patients, and compared them with changes in physiological measures. METHODS: Eighty-seven outpatients with stable asthma after 6 months of treatment were recruited. Health status using the Asthma Quality of Life Questionnaire (AQLQ) and the St. George's Respiratory Questionnaire (SGRQ), pulmonary function, peak expiratory flow (PEF) values, and airway hyperresponsiveness (AHR) were evaluated at entry and every year over a 5-year period. RESULTS: Using mixed effects models to estimate the slopes, the overall AQLQ score declined statistically at a mean rate of 0.06 units/year (P=.0091). However, this decline did not reach a clinically significant level at 5 years. The total SGRQ score did not change significantly (P=.54). Although the forced expiratory volume in 1 sec declined at a mean rate of 53 mL/year, the PEF variability and AHR improved significantly. CONCLUSION: Health status was clinically stable over the 5-year study period in patients with asthma, which contrasted with the changes in the physiological outcome measures. As a patient centered outcome measure, health status should be followed separately.

Exercise capacity deterioration in patients with COPD: longitudinal evaluation over 5 years.

BACKGROUND: Although exercise capacity is an important outcome measure in patients with COPD, its longitudinal course has not been analyzed in comparison to the change in pulmonary function. PURPOSES: To examine how exercise capacity would deteriorate over time in patients with COPD, and what factors would contribute to it. METHODS: A total of 137 male outpatients with moderate-to-very-severe COPD were examined. The average age was 69.0 +/- 6.6 years (+/- SD), and the mean postbronchodilator FEV(1) was 45.9 +/- 15.4% predicted. Progressive cycle ergometry and pulmonary function testing were performed at entry, and every 6 months thereafter over 5 years. Due to the presence of missing data, a mixed-effect model analysis was then used to estimate the longitudinal changes in various clinical parameters. RESULTS: Peak oxygen uptake (Vo(2)), peak minute ventilation (Ve), and peak tidal volume (Vt) during exercise declined significantly over time (p < 0.0001), which was no less rapid than the deterioration in FEV(1). The mean decline rates for peak Vo(2) were 32 +/- 60 mL/min/yr and 0.5 +/- 1.0 mL/min/kg/yr. Multiple regression analysis revealed that the changes in peak Ve, peak Vt, and peak respiratory rates were significant predictors for the change in peak Vo(2). CONCLUSION: We demonstrated clear evidence of measurable and progressive deterioration in exercise capacity in COPD patients, which was no less rapid than the decline in airflow limitation. Dynamic ventilatory constraints during exercise also deteriorated over time, which most significantly contributed to this exercise capacity deterioration. In addition to pulmonary function, the longitudinal follow-up of exercise capacity is important not to miss the overall deterioration in COPD.

Invasive aspergillosis in the aortic arch with infectious Aspergillus lesions in pulmonary bullae.

A patient with pulmonary bullae died of massive hemoptysis. At autopsy a hole was observed in the aortic wall. A microscopic examination indicated small Aspergillus lesions in pulmonary bullae and extensive necrotic lesions with Aspergillus hyphae in the media of the thoracic aorta. These findings led to a diagnosis of invasive aspergillosis in the aortic arch. This is a rare case in which Aspergillus invaded the aorta in a patient without hematologic neoplasms or neutropenia.

Dyspnea is a better predictor of 5-year survival than airway obstruction in patients with COPD.

BACKGROUND: FEV(1) is regarded as the most significant correlate of survival in COPD and is used as a measure of disease severity in the staging of COPD. Recently, however, the categorization of patients with COPD on the basis of the level of dyspnea has similarly been reported to be useful in the prediction of health-related quality of life and improvement in exercise performance after pulmonary rehabilitation. STUDY OBJECTIVES: We compared the effects of the level of dyspnea and disease severity, as evaluated by airway obstruction, on the 5-year survival rate of patients with COPD. DESIGN AND METHODS: A total of 227 patients with COPD were enrolled in a 5-year, prospective, multicenter study in the Kansai area of Japan, involving 20 divisions of respiratory medicine from various university and city hospitals. RESULTS: After 5 years, 183 patients were available for the follow-up examination (follow-up rate, 81%). The 5-year cumulative survival rate among patients with COPD was 73%. The effect of disease staging, based on the American Thoracic Society (ATS) guideline as evaluated by the percentage of predicted FEV(1), on the 5-year survival rate was not significant (p = 0.08). However, the level of dyspnea was significantly correlated to the 5-year survival rate (p < 0.001). The Cox proportional hazards model revealed that the level of dyspnea had a more significant effect on survival than disease severity based on FEV(1). CONCLUSIONS: The categorization of patients with COPD on the basis of the level of dyspnea was more discriminating than staging of disease severity using the ATS guideline with respect to 5-year survival. Dyspnea should be included as one of the variables, in addition to airway obstruction, for evaluating patients with COPD in terms of mortality.

Risk and severity of COPD is associated with the group-specific component of serum globulin 1F allele.

BACKGROUND: The finding that only 15 to 20% of cigarette smokers acquire COPD suggests that there is a genetic predisposition to the disease. Genetic polymorphism of the group-specific component of serum globulin (Gc-globulin), also known as vitamin-D-binding protein, is considered one of the candidates for the susceptibility to COPD. However, the role of Gc-globulin polymorphism in the development of COPD remains inconclusive. STUDY OBJECTIVE: s: To determine whether Gc-globulin gene polymorphism plays a role in the development of COPD in the Japanese population, and whether it is associated with the physiologic deterioration in COPD, and its radiologically detectable correlates. DESIGN: Association study. SUBJECTS AND METHODS: One hundred three patients with COPD and 88 healthy smokers sampled from the Japanese population were genotyped for Gc-globulin by the restriction fragment-length polymorphism method. Based on the results of the genotyping, we investigated the relationship between Gc-globulin polymorphism and a physiologic/radiologic indicator of lung function, namely, the annual decline of FEV(1) (dFEV(1)) in 86 patients with COPD and 21 healthy smokers. Additionally, high-resolution CT parameters such as low-attenuation area percentage (LAA%) and average CT number (mean CT score) were measured in 85 patients with COPD. RESULTS: There was an increased proportion of Gc*1F homozygotes in the patients with COPD (32%) compared with the healthy smokers (17%) [p = 0.01; odds ratio, 2.3; 95% confidence interval, 1.2 to 4.6]. Patients with COPD and the Gc*1F allele showed a larger dFEV(1) (p = 0.01), higher frequency with LAA% > 60% (p = 0.01), and lower mean CT score than patients without this allele (p = 0.03). CONCLUSION: Gc-globulin polymorphism is significantly associated with susceptibility to COPD, and also with the severity of the disease.

Comparison of the responsiveness of different disease-specific health status measures in patients with asthma.

BACKGROUND: Disease-specific health status measures are characterized by higher responsiveness than generic measures and may be preferred in clinical trials. However, comparisons of responsiveness between various disease-specific measures have rarely been performed in asthma studies. STUDY OBJECTIVE: We investigated and compared the responsiveness of health status scores in asthmatic patients during treatment using three different disease-specific measures: the Juniper Asthma Quality of Life Questionnaire (AQLQ), the Living with Asthma Questionnaire (LWAQ), and the Airways Questionnaire 20 (AQ20). METHODS: We attempted to follow up 170 patients with newly diagnosed asthma over a 6-month period. Patients underwent treatment with inhaled corticosteroids in accordance with the guideline. A health status evaluation using three disease-specific measures, and pulmonary function tests were performed on the initial visit, and at 3 months and 6 months. The effect size and the standardized response mean were used as responsiveness indexes. RESULTS: A total of 109 patients completed the 6-month follow-up and were then analyzed. All health status scores and FEV(1) measures improved during the first 3 months (p < 0.001). The total of the AQLQ scores showed high responsiveness indexes ranging from 1.28 to 1.46 between baseline and 3 months, and baseline and 6 months. Spearman correlation coefficients were smaller between the change in FEV(1) and the change in the LWAQ. Although the AQ20 also demonstrated high responsiveness, a ceiling effect was indicated. CONCLUSIONS: The AQLQ was the most responsive measure during asthma treatment. The relationship between the change in airflow limitation and the change in the LWAQ was weaker compared to the AQLQ and the AQ20. Although the AQ20 was also responsive and its simplicity is favorable, the ceiling effect should be considered when using it.