The Japanese Respiratory Society guidelines may reduce unnecessary chest computed tomography in patients with pneumonia requiring hospitalization: A retrospective study

BackgroundWith the abundance of CT scanners in Japan, doctors can easily order CT scans to diagnose pneumonia. The Japanese Respiratory Society (JRS) guidelines uniquely recommend conditions for which additional CT scans should be considered at the time of diagnosis of pneumonia, a feature not found in other guidelines. In this study, we aimed to evaluate the usefulness of the recommendations in a bid to reduce the number of unnecessary CT examinations.MethodsWe retrospectively reviewed the electronic medical records of consecutive patients with pneumonia hospitalized between April 2016 and March 2017 to extract patients’ backgrounds and clinical courses. Conformity with the JRS guideline recommendations was also examined. In the patients who did not meet the recommendations, we investigated the proportion of them for whom an additional CT scan influenced the clinical decisions. Finally, we evaluated whether there was a difference in hospital stay depending on the additional chest CT at the time of admission.ResultsWe included 363 hospitalized patients with pneumonia. Chest CT scan was performed in 306 patients (84.3%), of whom 186 (60.8%) did not meet the JRS guideline recommendations. Chest CT revealed findings requiring a change in treatment strategy in only 14 (7.5%) of the 186 patients. Among the 240 patients (66.1%) who did not meet the recommendations, no statistically significant difference was observed in the hospital stay or mortality between patients with and without CT scans.ConclusionsAdherence to the JRS guideline recommendations may reduce the excessive use of CT scans in the diagnosis of pneumonia.     

Evaluating a novel swallowing assessment as a predictor of mortality and recurring pneumonia in elderly patients with pneumonia

BackgroundAssessment of swallowing functions in elderly people with pneumonia is important. Videofluoroscopic and videoendoscopic examinations have been known as reliable assessments of swallowing functions. However, it is often difficult to use these tools in patients with pneumonia due to their poor condition and/or inadequate hospital facilities. We have previously constructed the Assessment of Swallowing Ability for Pneumonia (ASAP) as a straightforward evaluation for swallowing function. This study investigates the efficacy of the ASAP in predicting several outcomes in elderly patients with pneumonia.MethodsElderly patients with pneumonia (n = 130) who were admitted to Tobata Kyoritsu Hospital from January to June 2016 were enrolled prospectively. Associations between their ASAP scores and in-hospital mortality, recurrence of pneumonia within 30 days, 6-month mortality, and detection of antibiotic-resistant bacteria were evaluated.ResultsLower ASAP scores were associated with higher rates of in-hospital mortality, recurrence of pneumonia, and 6-month mortality. The areas under the curve were 0.84 (95% confidence interval [CI], 0.72–0.96) for in-hospital mortality, 0.76 (95% CI, 0.67–0.85) for recurrence of pneumonia, 0.74 (95% CI, 0.64–0.84) for 6-month mortality, and 0.67 (95% CI, 0.52–0.82) for detection of antibiotic-resistant bacteria. Multivariate analysis showed that a lower ASAP score was an independent risk factor for in-hospital mortality, recurrence of pneumonia, and 6-month mortality.ConclusionsThe ASAP was useful for predicting short- and long-term mortalities and recurrence of pneumonia.     

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.     

Effect of topical immunotherapy with squaric acid dibutylester for alopecia areata in Japanese patients

BackgroundThe Japanese guidelines for the treatment of alopecia areata list topical immunotherapies as a drug therapy for this condition. However, there is insufficient evidence of its efficacy to support this recommendation. Thus, we sought to clarify the effect of topical immunotherapy on the progression and severity of alopecia areata in Japanese patients.MethodsTo evaluate the effect of topical immunotherapy with squaric acid dibutylester (SADBE) in alopecia areata patients, we performed a retrospective cohort study on 49 alopecia patients who had received topical immunotherapy with SADBE. Patients were evaluated by the change in alopecia severity at 6 and 12 months after the initiation of topical immunotherapy. The improvement rate was calculated by determination of the complete and partial responses rate to treatment with topical immunotherapy by application of SADBE.ResultsThe improvement rate in all alopecia patients treated with SADBE topical immunotherapy was 57.8% (complete response; 11.1% and partial response; 46.7%).ConclusionsTopical immunotherapy with SADBE is an effective treatment for alopecia areata. Therefore, the current treatment recommendations for alopecia areata with topical immunotherapies are appropriate.     

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.     

Decrease in hemoglobin level predicts increased risk for severe respiratory failure in COVID-19 patients with pneumonia

BackgroundIn December 2019, the coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), emerged in Wuhan, China, and has since spread throughout the world. This study aimed to investigate the association between the change in laboratory markers during the three days after pneumonia diagnosis and severe respiratory failure in COVID-19 patients.MethodsData of 23 COVID-19 patients with pneumonia, admitted to the Kumamoto City Hospital between February and April 2020 were retrospectively analyzed.ResultsAmong the 23 patients, eight patients received mechanical ventilation (MV) (MV group), and the remaining 15 comprised the non-MV group. The levels of hemoglobin (Hb) and albumin (Alb) decreased in the MV group during the three days after pneumonia diagnosis more than in the non-MV group (median Hb: 1.40 vs. ?0.10 g/dL, P = 0.015; median Alb: 0.85 vs. ?0.30 g/dL, P = 0.020). Univariate logistic regression analysis showed that the decrease in Hb was associated with receiving MV care (odds ratio: 0.313, 95% confidence interval: 0.100–0.976, P = 0.045). Receiver operating characteristic curve analyses showed that the optimal cut-off value for the decrease in Hb level was ?1.25 g/dL, with sensitivity and specificity values of 0.867 and 0.750, respectively.ConclusionsThe decrease in Hb level during the short period after pneumonia diagnosis might be a predictor of worsening pneumonia in COVID-19 patients.     

Eicosanoids seasonally impact pulmonary function in asthmatic patients with Japanese cedar pollinosis

BackgroundCondition of asthma in patients with asthma and concomitant seasonal allergic rhinitis (SAR) deteriorates during the Japanese cedar pollen (JCP) season. However, the underlying mechanisms remain unclear.MethodsWe analyzed seasonal variations in eicosanoid levels in the airways of patients with asthma and concomitant SAR sensitized to JCP (N = 29, BA-SAR-JCP group) and those not sensitized (N = 13, BA-AR-non-JCP group) during the JCP season. The association between changes in eicosanoid concentrations and pulmonary function was assessed. Exhaled breath condensate (EBC) was collected, and pulmonary function tests were performed during the JCP and non-JCP seasons. The cysteinyl leukotriene (CysLT), thromboxane B₂ (TXB₂), prostaglandin D₂-methoxime (PGD₂-MOX), and leukotriene B₄ (LTB₄) levels in the collected EBC were measured via enzyme-linked immunosorbent immunoassays.ResultsThe log CysLT levels significantly increased in the BA-SAR-JCP group during the JCP season compared with the non-JCP season (1.78 ± 0.55, 1.39 ± 0.63 pg/mL, mean ± standard deviation, respectively, p = 0.01) and those in the BA-AR-non-JCP group during the JCP season (1.39 ± 0.38 pg/mL, p = 0.04). Moreover, the log TXB₂ levels seemed to increase. However, the log LTB₄ and log PGD₂-MOX levels did not increase. The changes in the log CysLT levels during the two seasons were negatively correlated to forced expiratory volume in one second (FEV₁) in the BA-SAR-JCP group (r = −0.52, p < 0.01).ConclusionsIn the BA-SAR-JCP group, seasonal increases in eicosanoid levels in the airway likely promoted deterioration in pulmonary function despite optimal maintenance treatment.     

Characteristics and association with survival of respiratory-related hospitalization in Japanese idiopathic pulmonary fibrosis patients

BackgroundThe characteristics and significance of respiratory-related hospitalization in patients with idiopathic pulmonary fibrosis (IPF) in Asian countries remain unknown. The purpose of this study was to define the characteristics of respiratory-related hospitalization and to inspect the relationship between respiratory-related hospitalization and subsequent survival in patients with IPF in Japanese general practice.MethodsPatients with IPF who underwent clinical evaluation between February 2008 and August 2017 were screened. Only those who had undergone evaluation within 1 year after the diagnosis of IPF were included in the study. The post-diagnosis pulmonary function tests were considered the registration point. We then performed a 6-month landmark analysis including only patients who were alive 6 months after the registration. The characteristics of respiratory-related hospitalizations during the 6 months after registration and the association between respiratory-related hospitalization and survival were investigated.ResultsA total of 106 patients with IPF were included in the study. The mean forced vital capacity (FVC) at registration was 80.2 ± 25.1% predicted. Seventeen patients (16.0%) had respiratory-related hospitalization during the 6 months after registration. Pneumonia was the most frequent reason for hospitalization (47.0%), followed by acute exacerbation of IPF (29.4%). In multivariate analysis, % predicted FVC (hazard ratio: 0.98, 95% confidence interval: 0.96–0.99, p = 0.004), 6-month decrease in % predicted FVC (1.05, 1.02–1.08, 0.005), and respiratory-related hospitalization (2.45, 1.24–4.85, 0.009) were significantly associated with survival.ConclusionsPneumonia is the most frequent cause of respiratory-related hospitalization in Japanese IPF patients. Furthermore, respiratory-related hospitalization is significantly associated with subsequent poor survival.     

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.     

Patient-Reported Outcome Measures Modestly Enhance Prediction of Readmission in Patients with Cirrhosis

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Prediction of long-term survival in patients with transfusion-dependent hemoglobinopathies: Insights from cardiac imaging and ferritin

AimsThe current study evaluated the association of echocardiography, cardiac magnetic resonance (CMR), and ferritin data with 10-year survival in thalassemia patients.MethodsDemographics, ferritin, echocardiography, and CMR parameters of stable consecutive thalassemia patients were prospectively collected.ResultsIn total, 75 patients (mean age 37 ± 11 years, 45% male) with thalassemia were included and dichotomized based on their survival status after a median follow-up period of 10.3 [9.6-10.9] years. Older age (HR: 1.071, p = 0.001), ferritin ≥2000 ng/ml (HR: 4.682, p = 0.007) and ≥1700 ng/ml (HR: 7.817, p = 0.002), elevated LV end-diastolic pressure (HR: 1.019, p = 0.044), TR Vmax >2.8 m/s (HR: 6.845, p = 0.005), and CMR T21 ≤20 msec (HR: 3.602, p = 0.043) and ≤34 msec (HR: 5.854, p = 0.026) were associated with increased all-cause mortality (primary endpoint). A baseline model including age was created and became more predictive of worse survival by adding TR Vmax >2.8 m/s instead of elevated LV end-diastolic pressure (C index 0.767 vs. 0.760, respectively), ferritin ≥1700 ng/ml instead of ≥2000 ng/ml (C index 0.890 vs. 0.807, respectively), or CMR T21≤34 msec instead of ≤20 msec (C index 0.845 vs. 0.839, respectively). Parameters associated with the combined endpoint of cardiac mortality/cardiac hospitalization (secondary endpoint) after adjusting for age were ferritin ≥1700 ng/ml (HR 3.770, p = 0.014), ratio E/A wave >2 (HR 3.565, p = 0.04), TR Vmax >2.8 m/s (HR 4.541, p = 0.049), CMR T21 ≤20 ms (HR 9.462, p = 0.001), and CMR T21 ≤34 ms (HR 11.735, p = 0.002). The model including age and T21 ≤34 ms instead of T21 ≤20 ms was more predictive of the secondary endpoint (C-index 0.844 vs 0.838, respectively).ConclusionsIn thalassemia patients, TR Vmax >2.8 m/s, ferritin ≥2000 ng/ml, and CMR T21 ≤20 ms were associated with worse long-term survival. In the current era of advanced chelation therapy, aiming for ferritin ≤1700 ng/ml and CMR T21 ≥34 ms may improve their prognosis.     

Long-term safety of Prolastin®-C,an alpha1-proteinase inhibitor,in Japanese patients with alpha1-antitrypsin deficiency

BackgroundSafety and pharmacokinetics (PK) of alpha₁-proteinase inhibitor, modified process (Alpha-1 MP), was evaluated in a clinical trial of Japanese patients with alpha₁-antitrypsin deficiency (AATD). The present study aimed to evaluate the long-term safety of weekly intravenous infusions of 60 mg/kg Alpha-1 MP in Japanese patients with AATD.MethodsThis was a multi-center, open-label extension (OLE) study that enrolled adult patients with AATD, who had completed the preceding safety and PK clinical trial. Patients were administered with Alpha-1 MP (60 mg/kg) weekly, for 52 weeks, and this could be renewed annually. Alpha1-MP trough levels (C_min) were evaluated, and safety endpoints include: treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), TEAEs potentially related to Alpha-1 MP, chronic obstructive pulmonary disease (COPD) exacerbations, laboratory parameters, vital signs, and pulmonary function tests (forced expiration volume in 1 s [FEV₁] and forced vital capacity [FVC]).ResultsFour patients underwent Alpha-1 MP intravenous infusions at a mean (SD) of 210.8 (9.54) for 213 weeks (four years), with a C_min of 55.73 (4.99) mg/dL. A total of fifty-four TEAEs were reported in four patients, in which most of them were mild (n = 52, 96.3%). Two patients had five SAEs, and all were unrelated to treatment. Three mild TEAEs were potentially related to treatment with Alpha-1 MP. No clinically significant findings in laboratory parameters, COPD exacerbations, or vital signs were observed. There were no identifiable differences in FEV₁ and FVC throughout the study period.ConclusionsLong-term weekly intravenous infusions of 60 mg/kg Alpha-1 MP are generally safe and well-tolerated in Japanese patients with AATD.Clinicaltrials.govNCT02870348; JAPIC CTI: JapicCTI-163194.     

Multifaceted analysis of Japanese cases of primary ciliary dyskinesia: Value of immunofluorescence for ciliary protein detection in patients with DNAH5 and DNAH11 mutations

Multifaceted analysis is recommended for the diagnosis of primary ciliary dyskinesia (PCD). A 31-year-old woman had situs inversus, bronchiectasis, family history of PCD, and compound heterozygous mutations in DNAH5. Her cilia were immotile. Defects in the outer dynein arms were revealed by transmission electron microscopy and loss of DNAH5 proteins in the entire length of axonemes using immunofluorescence (IF). A 17-year-old boy had bronchiectasis and heterozygous mutations in DNAH11. His cilia were motile with normal ultrastructure. The loss of DNAH11 proteins at the proximal region of cilia was revealed by IF. IF could be useful to support PCD diagnosis.     

Outcome of early-stage combination treatment with favipiravir and methylprednisolone for severe COVID-19 pneumonia: A report of 11 cases

Although the use of corticosteroids is not recommended in the World Health Organization statement for the treatment of coronavirus disease 2019 (COVID-19), steroid therapy may be indicated for critical cases in specific situations. Here, we report the successful treatment of 11 cases of severe COVID-19 pneumonia with favipiravir and methylprednisolone. All cases were severe and patients required oxygen administration or had a blood oxygen saturation ≤93% on room air. All were treated with favipiravir and methylprednisolone, and 10 of 11 patients responded well and required no further oxygen supplementation or ventilator management. This study shows the importance of the early-stage use of a combination of favipiravir and methylprednisolone in severe cases to achieve a favorable clinical outcome.     

Where is Chlamydophila pneumoniae pneumonia?

BackgroundMolecular diagnostic methods have recently gained widespread use, and consequently, the importance of viral pathogens in community-acquired pneumonia (CAP) has undergone re-evaluation. Under these circumstances, the role of Chlamydophila pneumoniae as a pathogen that causes CAP also needs to be reviewed.MethodsWe reviewed articles that contained data on the frequency of identification of C. pneumoniae pneumonia as a causative pathogen for CAP. The articles were identified by performing a search in PubMed with the keywords “community-acquired pneumonia” and “pathogen”.ResultsSixty-three articles were identified. The reviewed articles demonstrated that the rates of identification of C. pneumoniae as the causative pathogen for CAP were significantly lower in assessments based on polymerase chain reaction (PCR) methods than in those based on serological methods. In some studies, it was possible to compare both serological and PCR methods directly using the same set of samples.ConclusionsThe use of PCR methods, including multiplex PCR assays, has revealed that C. pneumoniae may play a limited role as a pathogen for CAP.     

Long-term treatment of Japanese cedar pollinosis with Japanese cedar pollen SLIT drops and persistence of treatment effect: A post-marketing clinical trial

BackgroundThere have been no reports of treatment effect persistence after long-term sublingual immunotherapy (SLIT) in patients with Japanese cedar (JC) pollinosis. Therefore, we conducted a post-marketing clinical trial to investigate the efficacy, safety, and effect persistence of JC pollen SLIT drops after approximately 3 years of treatment.MethodsThis was an open-label trial of 233 patients with JC pollinosis who were treated with JC pollen SLIT drops for approximately 3 years (2015–2017) and followed-up for an additional 2 years (2018–2019). Efficacy and effect persistence were evaluated using nasal and ocular symptom scores, daily use of rescue medication, and Japanese Rhinoconjunctivitis Quality of Life Questionnaire scores recorded during the JC pollen dispersal season of each year. Safety was evaluated by monitoring adverse events and adverse drug reactions.ResultsThe mean combined total nasal symptom and medication score (range 0–18) during the peak symptom periods of 2015 through 2019 were 5.47 ± 3.38, 4.52 ± 3.13, 3.58 ± 2.63, 5.28 ± 4.01, and 6.83 ± 4.65, respectively. The percentage of patients who used no rescue medications during the same periods was 64.8%, 75.2%, 80.3%, 63.7%, and 50.3%, respectively. A total of 138 adverse drug reaction incidents were recorded in 73 of the 233 patients (31.3%), of which 134 incidents (97.1%) were mild in severity.ConclusionsJC pollen SLIT drops demonstrated treatment duration-dependent efficacy with effects that persisted for 2 years after cessation of treatment. The drug had a favorable safety profile over the 5-year study period.     

Effects of nintedanib on disease progression and safety in Japanese patients with progressive fibrosing interstitial lung diseases: Further subset analysis from the whole INBUILD trial

BackgroundA previous subgroup analysis of data from the INBUILD trial showed that nintedanib reduced the annual rate of decline in forced vital capacity (FVC) in Japanese patients with progressive fibrosing interstitial lung diseases (PF-ILDs). The safety profile of nintedanib over 52 weeks in Japanese patients was similar to that of the overall population.MethodsUsing data from 108 Japanese patients with PF-ILDs who had received at least 1 dose of study medication in the INBUILD trial, we evaluated the effect of nintedanib on disease progression and assessed the safety profile over the whole trial period (i.e., a longer duration than the prior analysis) compared with placebo. ILD progression was defined as an absolute decline in FVC ≥10% predicted vs baseline.ResultsOver the whole trial, in Japanese patients with PF-ILDs, nintedanib numerically lowered the risk of progression of ILD or death (hazard ratio [HR], 0.66; 95% confidence intervals [CI]: 0.37, 1.16), acute exacerbation of ILD or death (HR, 0.28; 95% CI: 0.09, 0.83), and death (HR, 0.41; 95% CI: 0.11, 1.51). The most common adverse event over the whole trial in nintedanib-treated Japanese patients was diarrhea, which was manageable for most patients by dose reduction and interruption. The safety profile of nintedanib in this longer duration analysis was consistent with that previously reported.ConclusionsIn this analysis of data from Japanese patients with PF-ILDs, nintedanib nominally reduced the risk of clinically meaningful outcomes reflecting disease progression, including death, over the whole trial, and no new safety concerns were observed.Clinical trial registrationClinicalTrials.gov NCT02999178.