Nationwide survey in Japan of the causative diseases of bloody sputum and hemoptysis in departments of respiratory medicine at university hospitals and core hospitals.

BACKGROUND: The Guidelines for the Management of Cough and Sputum (2019) of the Japanese Respiratory Society (JRS) were the first internationally published guidelines for the management of sputum. However, the data used to determine the causative diseases of bloody sputum and hemoptysis in these guidelines were not obtained in Japan. METHODS: A retrospective analysis was performed using the clinical information of patients with bloody sputum or hemoptysis who visited the department of respiratory medicine at a university or core hospital in Japan. RESULTS: Included in the study were 556 patients (median age, 73 years; age range, 21-98 years; 302 males (54.3%)). The main causative diseases were bronchiectasis (102 patients (18.3%)), lung cancer (97 patients (17.4%)), and non-tuberculous mycobacterial disease (89 patients (16%)). Sex and age differences were observed in the frequency of causative diseases of bloody sputum and hemoptysis. The most common cause was lung cancer in males (26%), bronchiectasis in females (29%), lung cancer in patients aged <65 years (19%), and bronchiectasis in those aged >65 years (20%). CONCLUSIONS: The present study is the first to investigate the causative diseases of bloody sputum and hemoptysis using data obtained in Japan. When investigating the causative diseases of bloody sputum and hemoptysis, it is important to take the sex and age of the patients into account.

The Clinical Significance of Anaerobic Coverage in the Antibiotic Treatment of Aspiration Pneumonia: A Systematic Review and Meta-Analysis.

INTRODUCTION: Aspiration pneumonia is increasingly recognised as a common condition. While antibiotics covering anaerobes are thought to be necessary based on old studies reporting anaerobes as causative organisms, recent studies suggest that it may not necessarily benefit prognosis, or even be harmful. Clinical practice should be based on current data reflecting the shift in causative bacteria. The aim of this review was to investigate whether anaerobic coverage is recommended in the treatment of aspiration pneumonia. METHODS: A systematic review and meta-analysis of studies comparing antibiotics with and without anaerobic coverage in the treatment of aspiration pneumonia was performed. The main outcome studied was mortality. Additional outcomes were resolution of pneumonia, development of resistant bacteria, length of stay, recurrence, and adverse effects. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: From an initial 2523 publications, one randomised control trial and two observational studies were selected. The studies did not show a clear benefit of anaerobic coverage. Upon meta-analysis, there was no benefit of anaerobic coverage in improving mortality (Odds ratio 1.23, 95% CI 0.67-2.25). Studies reporting resolution of pneumonia, length of hospital stay, recurrence of pneumonia, and adverse effects showed no benefit of anaerobic coverage. The development of resistant bacteria was not discussed in these studies. CONCLUSION: In the current review, there are insufficient data to assess the necessity of anaerobic coverage in the antibiotic treatment of aspiration pneumonia. Further studies are needed to determine which cases require anaerobic coverage, if any.

Characteristics of patients with viral infections of the lower respiratory tract: A retrospective study.

While the impact of respiratory virus infections has been well researched in some respiratory diseases, no clinical studies have discussed the subject of who would be more likely to develop respiratory virus infections among patients with various respiratory illnesses who come from different backgrounds. This study aimed to identify respiratory diseases that are frequently associated with respiratory virus infections along with the characteristics of patients who develop such infections in clinical settings. Tested specimens were obtained from the lower respiratory tract by bronchoscopy to provide more accurate data. Data of bronchoscopies at Ryukyu University Hospital between August 2012 and September 2016 were reviewed, and patients who underwent multiplex polymerase chain reaction (PCR) tests for detecting respiratory viruses in bronchoscopy specimens were retrospectively recruited for descriptive statistics. Differences among patients' primary pulmonary diseases and backgrounds were compared between the PCR-positive and -negative patients, and multivariate statistical analysis was performed to analyze factors associated with a positive PCR test result. Overall, 756 bronchoscopies were performed during the study period and PCR tests were performed for 177 patients. Of them, 27 tested positive for respiratory viruses, mainly parainfluenza virus and rhinovirus, and out of those, 7 were hospitalized for >1 month. Overall, all patients did not experience typical upper respiratory infection symptoms. In positive patients, 13 and 7 had diagnoses of interstitial lung disease and bacterial pneumonia, respectively. The diagnoses of 3 bacterial pneumonia cases were changed to viral pneumonia after receiving their PCR-positive tests. Respiratory virus infections were confirmed in 14 patients on immunosuppressant therapy and 4 on maintenance dialysis. Multivariate analysis revealed that immunosuppressant therapy and maintenance dialysis were independently associated with respiratory virus infections. Viruses were commonly detected in patients with interstitial lung diseases and bacterial pneumonia, while few patients were diagnosed with pure viral pneumonia. These illnesses were considered to be induced by respiratory infections. Immunosuppressant therapy and maintenance dialysis were associated with respiratory virus infections. Multiplex PCR testing is an essential diagnostic tool for respiratory virus infections in immunocompromised patients.

The Japanese respiratory society guidelines for the management of cough and sputum (digest edition).

Cough and sputum are common complaints at outpatient visits. In this digest version, we provide a general overview of these two symptoms and discuss the management of acute (up to three weeks) and prolonged/chronic cough (longer than three weeks). Flowcharts are provided, along with a step-by-step explanation of their diagnosis and management. Most cases of acute cough are due to an infection. In chronic respiratory illness, a cough could be a symptom of a respiratory infection such as pulmonary tuberculosis, malignancy such as a pulmonary tumor, asthma, chronic obstructive pulmonary disease, chronic bronchitis, bronchiectasis, drug-induced lung injury, heart failure, nasal sinus disease, sinobronchial syndrome, eosinophilic sinusitis, cough variant asthma (CVA), atopic cough, chronic laryngeal allergy, gastroesophageal reflux (GER), and post-infectious cough. Antibiotics should not be prescribed for over-peak cough but can be considered for atypical infections. The exploration of a single/major cause is recommended for persistent/chronic cough. When sputum is present, a sputum smear/culture (general bacteria, mycobacteria), cytology, cell differentiation, chest computed tomography (CT), and sinus X-ray or CT should be performed. There are two types of rhinosinusitis. Conventional sinusitis and eosinophilic rhinosinusitis present primarily with neutrophilic inflammation and eosinophilic inflammation, respectively. The most common causes of dry cough include CVA, atopic cough/laryngeal allergy (chronic), GER, and post-infectious cough. In the last chapter, future challenges and perspectives are discussed. We hope that the clarification of the pathology of cough hypersensitivity syndrome will lead to further development of "pathology-specific non-specific therapeutic drugs" and provide benefits to patients with chronic refractory cough.

A long-term survivor keeping in a complete response without treatment after pemetrexed maintenance therapy for advanced non-squamous non-small cell lung cancer.

Pemetrexed has significant efficacy for some non-squamous non-small cell lung cancer cases, as demonstrated in the current case. For those patients, pemetrexed administration should be carefully considered.

Human immunodeficiency virus-associated pulmonary sarcoidosis in a Japanese man as a manifestation of immune reconstitution inflammatory syndrome.

Asymptomatic pulmonary sarcoidosis can develop after starting antiretroviral therapy. The decision on whether to treat sarcoidosis with corticosteroids should be based on the disease severity.

Clinical characteristics of community-acquired pneumonia due to Moraxella catarrhalis in adults: a retrospective single-centre study.

BACKGROUND: Although Moraxella catarrhalis (M. catarrhalis) is a common cause of community-acquired pneumonia (CAP), studies investigating clinical manifestations of CAP due to M. catarrhalis (MC-CAP) in adults are limited. Since S. pneumoniae is the leading cause of CAP globally, it is important to distinguish between MC-CAP and CAP due to S. pneumoniae (SP-CAP) in clinical practice. However, no past study compared clinical characteristics of MC-CAP and SP-CAP by statistical analysis. We aimed to clarify the clinical characteristics of MC-CAP by comparing those of SP-CAP, as well as the utility of sputum Gram staining. METHODS: This retrospective study screened CAP patients aged over 20 years visiting or admitted to Okinawa Miyako Hospital between May 2013 and April 2018. Among these, we included patients whom either M. catarrhalis alone or S. pneumoniae alone was isolated from their sputum by bacterial cultures. RESULTS: We identified 134 MC-CAP and 130 SP-CAP patients. Although seasonality was not observed in SP-CAP, almost half of MC-CAP patients were admitted in the winter. Compared to those with SP-CAP, MC-CAP patients were older (p < 0.01) and more likely to have underlying pulmonary diseases such as asthma and bronchiectasis (p < 0.01). Approximately half of asthmatic MC-CAP and SP-CAP patients had asthma attacks. Although winter is an influenza season in Japan, co-infection with influenza virus was less common in MC-CAP compared to SP-CAP patients (3% vs. 15%, p < 0.01). Bronchopneumonia patterns on X-ray, as well as bronchial wall thickening, bilateral distribution, and segmental pattern on CT were more common in MC-CAP patients than in SP-CAP patients (p < 0.01). Sputum Gram stain was highly useful method for the diagnosis in both MC-CAP and SP-CAP (78.4% vs. 89.2%), and penicillins were most frequently chosen as an initial treatment for both pneumonias. CONCLUSIONS: This is the first study to show that MC-CAP occurred in older people compared to SP-CAP, influenza virus co-infection was less common in MC-CAP than SP-CAP, and that MC-CAP frequently caused asthma attacks. Gram stain contributed for the appropriate treatment, resulting in conserving broad-spectrum antibiotics such as cephalosporins and fluoroquinolones in both MC-CAP and SP-CAP patients.

Use of steroids to treat anti-tumor necrosis factor α induced tuberculosis-associated immune reconstitution inflammatory syndrome: Case report and literature review.

INTRODUCTION: Individuals with tuberculosis (TB) who are being treated with anti-tumor necrosis factor α (anti-TNFα) for coexisting conditions may experience unexpected exacerbations of TB after the initiation of antituberculous therapy, so-called anti-TNFα-induced TB-immune reconstitution inflammatory syndrome (anti-TNFα-induced TB-IRIS). Anti-TNFα-induced TB-IRIS is often treated empirically with corticosteroids; however, the evidence of the effectiveness of corticosteroids is lacking and the management can be a challenge. PATIENT CONCERNS: A 32-year-old man on long-term infliximab therapy for Crohn disease visited a clinic complaining of persistent fever and cough that had started 1 week previously. His most recent infliximab injection had been administered 14 days before the visit. A chest X-ray revealed a left pleural effusion, and he was admitted to a local hospital. DIAGNOSIS: A chest computed tomography (CT) scan revealed miliary pulmonary nodules; acid-fast bacilli were found in a sputum smear and a urine sediment sample; and polymerase chain reaction confirmed the presence of Mycobacterium tuberculosis in both his sputum and the pleural effusion. He was diagnosed with miliary TB. INTERVENTIONS: Antituberculous therapy was started and he was transferred to our hospital for further management. His symptoms initially improved after the initiation of antituberculous therapy, but 2 weeks later, his symptoms recurred and shadows on chest X-ray worsened. A repeat chest CT scan revealed enlarged miliary pulmonary nodules, extensive ground-glass opacities, and an increased volume of his pleural effusion. This paradoxical exacerbation was diagnosed as TB-IRIS associated with infliximab. A moderate-dose of systemic corticosteroid was initiated [prednisolone 25 mg/day (0.5 mg/kg/day)]. OUTCOMES: After starting corticosteroid treatment, his radiological findings improved immediately, and his fever and cough disappeared within a few days. After discharge, prednisolone was tapered off over the course of 10 weeks, and he completed a 9-month course of antituberculous therapy uneventfully. He had not restarted infliximab at his most recent follow-up 14 months later. CONCLUSION: We successfully managed a patient with anti-TNFα-induced TB-IRIS using moderate-dose corticosteroids. Due to the limited evidence currently available, physicians should consider the necessity, dosage, and duration of corticosteroids for each case of anti-TNFα-induced TB-IRIS on an individual patient-by-patient basis.

Acute Hypertriglyceridaemia Caused by Tocilizumab in a Patient with Severe COVID-19.

Treatment with tocilizumab (TCZ) to block interleukin-6 (IL-6) signalling is predicted to mitigate cytokine release syndrome (CRS) caused by coronavirus disease 2019 (COVID-19). However, the adverse effects of TCZ on patients with COVID-19 remain unclear. We herein report a patient with COVID-19 treated with TCZ who developed acute hypertriglyceridaemia. Despite favipiravir treatment, acute respiratory distress syndrome developed in a 45-year-old patient with COVID-19; thus, TCZ was initiated. The triglyceride levels greatly increased after TCZ administration. Physicians should consider the negative impact of TCZ on the lipid profile in patients with COVID-19, although COVID-19-induced CRS itself may be an aggravating factor.

A Case Report of Cerebral Meningitis Caused by Penicillin-Non-Susceptible Group B Streptococcus in an Immunocompromised Adult Patient.

Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is the leading cause of bacteremia and meningitis in neonates; however, it also causes meningitis in adults, although much less frequently. After the detection of penicillin-non-susceptible GBS (PRGBS) for the first time in 2008 by Japanese researchers, clinical PRGBS isolates have been reported worldwide. These isolates need to be given due attention for being non-susceptible to multiple drugs. Herein, we present the first clinical report of meningitis caused by PRGBS. A 41-year-old Japanese male receiving an immunosuppressant visited hospital complaining of fever. Although he did not have meningitis-related symptoms or physical findings, determination of the cause of fever by Gram-staining of the spinal fluid revealed gram-positive cocci in pairs and chains. Initially, he was hospitalized on the diagnosis of cerebral meningitis caused by Streptococcus pneumoniae. However, culture of the spinal fluid revealed the ß-hemolytic colonies on blood agar. Biochemical testing and mass spectrometry revealed the isolated organism as GBS (serotype Ib). The minimum inhibitory concentration (MIC) of penicillin G for the isolated strain was 0.5 µg/mL, which is greater than the MIC criteria for "susceptibility" to penicillin G for beta-hemolytic streptococci according to Clinical and Laboratory Standards Institute standards. The isolated strain was also resistant to macrolide (MIC ≥ 8 µg/mL) and fluoroquinolone (MIC ≥ 8 µg/mL). The patient recovered without neurologic sequelae upon treatment with ceftriaxone, vancomycin, and corticosteroids for 4 days, and subsequently with ampicillin for 17 days. The rate of isolation of PRGBS in the clinics has gradually increased, particularly in Japan. Although PRGBS isolated in the present case was susceptible to ampicillin and cephalosporins, strains not susceptible to ampicillin, cefotaxime, and ceftriaxone have already been isolated, indicating the prospects for limited range of effective antibiotics against PRGBS infections, including meningitis, in the near future.

The First Case of Community-Acquired Pneumonia Due to Capsular Genotype K2-ST86 Hypervirulent Klebsiella pneumoniae in Okinawa, Japan: A Case Report and Literature Review.

Hypervirulent Klebsiella pneumoniae (HV-KP) typically causes pyogenic liver abscess and bacteremia with metastatic infections. Community-acquired pneumonia (CAP) due to HV-KP is uncommon and details of its clinical and microbiological features are limited. We report the first case of CAP due to capsular genotype K2-ST86 HV-KP in Okinawa, Japan and review infections caused by the K2-ST86 strain. A 79-year-old woman presenting with fever and productive cough persisting for the past three days was admitted to hospital. Her vital signs indicated septic shock. Lung examination by auscultation revealed holo-crackle and lobar pneumonia in chest radiography, and Streptococcus pneumoniae was suspected. However, sputum and blood cultures revealed Gram-negative coccus identified as K. pneumoniae. Genetic analysis identified the isolated strain as the K2 serotype harboring rmpA, iutA, entB, and mrkD. Therefore, we identified the isolated strain as hypervirulent. The isolate belonged to ST86 as determined by multilocus sequence typing. The case was not complicated by predisposing factors such as diabetes mellitus and malignancy related to HV-KP infection; thus, this CAP-causing HV-KP strain may differ from the typical HV-KP strain that induces liver abscess. A literature review identified only nine cases with CAP due to HV-KP. In all cases, the disease mainly occurred in older males with diabetes mellitus, which makes the present case unusual, and had high rates of septic shock and death. No case, including ours, was complicated by metastatic infection, suggesting that CAP due to HV-KP poses little distant metastasis risk, even in patients with bloodstream infection. In our review, consistent with our case, K2-ST86 was the most common strain of HV-KP in patients with CAP. Therefore, studies are needed to elucidate the clinical and microbiological features of HV-KP CAP, with a focus on the K2-ST86 strain. Physicians should always consider K. pneumoniae in cases of sepsis CAP with lobar pneumonia.

Case Report of Primary Lung Abscesses Due to Hypervirulent Klebsiella pneumoniae (Serotype K2, Sequence Type 375): an Emerging Isolate in Okinawa, Japan.

Hypervirulent Klebsiella pneumoniae (HV-KP) is typically associated with community-acquired liver abscess and bacteremia with metastatic infection; however, primary lung abscess (PLA) caused by HV-KP is rare, with only one such case report to date. A 69-year-old man with a history of diabetes mellitus (DM) was admitted to hospital complaining of slight bloody sputum. Chest imaging showed multiple consolidations with cavities in both lung fields. A culture of bronchoalveolar lavage fluid confirmed the presence of K. pneumoniae. Genetic analyses identified the isolate as serotype K2 and sequence type 375 (K2-ST375), and that it harbored the rmpA gene. The patient was an Asian middle-aged male with DM, all of which are risk factors for HV-KP infection. Although complicating DM and the presence of the rmpA gene are more likely to induce disseminated infection, metastatic infections were not found in this patient. The clinical and microbiological characteristics of our patient were different from those of a previous reported case, although in both cases the patient was from Asia and had DM. Therefore, DM appears to be one of the predisposing factors for HV-KP lung abscesses and physicians should pay attention to emerging HV-KP lung abscess infection, particularly in Asian countries. Previous studies have also revealed that K2-ST375 is one of the major clones causing HV-KP infection, and that it is mainly isolated from patients with liver abscess. Interestingly, including the present case, most of the infectious cases caused by K2-ST375 have been reported from Okinawa Prefecture in Japan. Therefore, the trend of the K2-ST375 strain should be carefully monitored, particularly in Okinawa, Japan. The serotype of HV-KP that causes PLA is still unknown and further study is needed to elucidate the etiology of PLA due to HV-KP and the relationship between the strain K2-ST375 and PLA.

Analysis of bronchoalveolar lavage samples collected from 30 patients with drug-induced pneumonitis.

BACKGROUND: Drug-induced pneumonitis is a disease encountered by pulmonologists in the clinical setting. The diagnosis generally considers the patient's clinical course and the results of peripheral blood tests, radiological examinations, and often bronchoscopic examinations. However, few studies have reported the association between radiological patterns such as ground-glass opacity (GGO) or consolidation, and bronchoalveolar lavage fluid (BALF) cell fractions. This study aimed to clarify this association. METHODS: Patients with a Naranjo's score of probable or definite were enrolled, and all 30 patients were categorized under probable. Data such as patient background, blood examination results, radiological findings, and BALF cell fractions were retrospectively collected. The association between BALF cell fractions and other factors such as chest computed tomography (CT) findings was evaluated. RESULTS: The most common radiological finding in patients with lymphocyte-dominant BALF was GGO, with only one patient exhibiting consolidation. However, patients with eosinophil-dominant BALF were more likely to have consolidation; only three cases showed crazy paving and one showed GGO. In addition, patients with a GGO-dominant pattern on CT had an increased lymphocyte fraction of 41.0%; those with a consolidation-dominant pattern showed a relatively high eosinophil fraction of 5.2%; and those with a crazy paving pattern showed elevated eosinophil and neutrophil fractions of 19.1% and 9.9%, respectively. CONCLUSIONS: In this study, a remarkable difference in radiological findings was observed among different BALF patterns.

Diagnostic performance of serum interferon gamma, matrix metalloproteinases, and periostin measurements for pulmonary tuberculosis in Japanese patients with pneumonia.

Serum markers that differentiate between tuberculous and non-tuberculous pneumonia would be clinically useful. However, few serum markers have been investigated for their association with either disease. In this study, serum levels of interferon gamma (IFN-γ), matrix metalloproteinases 1 and 9 (MMP-1 and MMP-9, respectively), and periostin were compared between 40 pulmonary tuberculosis (PTB) and 28 non-tuberculous pneumonia (non-PTB) patients. Diagnostic performance was assessed by analysis of receiver-operating characteristic (ROC) curves and classification trees. Serum IFN-γ and MMP-1 levels were significantly higher and serum MMP-9 levels significantly lower in PTB than in non-PTB patients (p < 0.001, p = 0.002, p < 0.001, respectively). No significant difference was observed in serum periostin levels between groups. ROC curve analysis could not determine the appropriate cut-off value with high sensitivity and specificity; therefore, a classification tree method was applied. This method identified patients with limited infiltration into three groups with statistical significance (p = 0.01), and those with MMP-1 levels < 0.01 ng/mL and periostin levels ≥ 118.8 ng/mL included only non-PTB patients (95% confidence interval 0.0-41.0). Patients with extensive infiltration were also divided into three groups with statistical significance (p < 0.001), and those with MMP-9 levels < 3.009 ng/mL included only PTB patients (95% confidence interval 76.8-100.0). In conclusion, the novel classification tree developed using MMP-1, MMP-9, and periostin data distinguished PTB from non-PTB patients. Further studies are needed to validate our cut-off values and the overall clinical usefulness of these markers.

Comparison of two screening tests for HIV-Associated Neurocognitive Disorder suspected Japanese patients with respect to cART usage.

In this study, we demonstrated the pervasiveness of HIV-associated neurocognitive disorders (HAND) among a selection of Japanese patients as well as evaluated and compared the Mini Mental State Examination (MMSE) and the International HIV Dementia Scale (IHDS) for use as a screening tool among combination anti-retroviral therapy (cART)-naïve and cART experienced patients. The MMSE and the IHDS have both been used as HAND screening tests around the world with variable success. It has been reported the increased usage of cART the utility of these screening tests may have been diminished due to the decreased severity of impairment and the altered pattern of neurocognitive impairments in cART era HAND patients. It is therefore possible the MMSE and the IHDS may still be useful among cART-naïve patients even in the cART era. However, only one study has investigated and compared the screening results of the IHDS among cART-naïve and cART experienced patients. All HIV positive patients who visited, or were admitted, to the Ryukyu University Hospital between January 2009 and March 2014 were evaluated for inclusion. Selected patients (n = 49) had data without omission for all tests. The overall prevalence of HAND in our cohort was 44%. The area under the curve (AUC), for all subjects using the MMSE and the IHDS, were 0.60 and 0.69, respectively. However, the AUC among cART-naïve patients were 0.58 and 0.76 for the MMSE and the IHDS, respectively. Whereas, cART experienced patients had an AUC of 0.60 and 0.61, respectively. Overall, the MMSE demonstrated a poor screening ability for HAND, regardless of cART usage (the cut-off value of 27 had a Youden's J-Index of 0.1, in all groups). Alternatively, the IHDS was moderately useful for HAND screening among cART-naïve patients (the cut-off value of 11 had a Youden's J-Index of 0.4), but performed poorly as a screening test among cART experienced patients (the cut-off value of 11 had a Youden's J-Index of 0.1).

Clinical Features of Human Metapneumovirus Pneumonia in Non-Immunocompromised Patients: An Investigation of Three Long-Term Care Facility Outbreaks.

Background: Several studies have reported outbreaks due to human metapneumovirus (hMPV) in long-term care facilities (LTCF) for the elderly. However, most of these reports are epidemiological studies and do not investigate the clinical features of hMPV pneumonia. Methods: Three independent outbreaks of hMPV occurred at separate LTCF for intellectually challenged and elderly residents. A retrospective evaluation of hMPV pneumonia and its clinical and radiological features was conducted using available medical records and data. Results: In 105 hMPV infections, 49% of patients developed pneumonia. The median age of pneumonia cases was significantly higher than non-pneumonia cases (P < .001). Clinical manifestations of hMPV pneumonia included high fever, wheezing in 43%, and respiratory failure in 31% of patients. An elevated number of white blood cells as well as increased levels of C-reactive protein, creatine phosphokinase, and both aspartate and alanine transaminases was also observed among pneumonia cases. Evaluation of chest imaging revealed proximal bronchial wall thickenings radiating outward from the hilum in most patients. Conclusions: The aforementioned characteristics should be considered as representative of hMPV pneumonia. Patients presenting with these features should have laboratory testing performed for prompt diagnosis.