Chronic Pulmonary Aspergillosis Caused by Aspergillus tubingensis Diagnosed by a Bronchoscopic Biopsy.

We herein report a case of chronic pulmonary aspergillosis (CPA) caused by Aspergillus tubingensis diagnosed by a bronchoscopic biopsy with negative serological and sputum culture findings. A 66-year-old man was referred for the assessment of a pulmonary cavity. Computed tomography showed a thick-walled cavity in the upper right pulmonary lobe. Serum ß-D glucan, Aspergillus galactomannan, and Aspergillus antibody tests were negative. Aspergillus species were not detected in the sputum. Culture and pathological specimens were obtained from the mass by bronchoscopy. Microscopic examination findings were consistent with Aspergillus niger complex morphologically and identified as Aspergillus tubingensis through DNA sequencing. The patient was diagnosed with chronic pulmonary aspergillosis.

Successful treatment with inhaled corticosteroid/long-acting ß2-agonist in a case of allergic bronchopulmonary mycosis caused by Schizophyllumcommune.

Allergic bronchopulmonary mycosis (ABPM) is a chronic immune-mediated pulmonary disease, which is caused by fungal infection of the airways. Aspergillus species are the main causative fungi and standard treatment typically comprises systemic corticosteroid therapy with or without adjunct antifungal agents. We describe our experience with a case of ABPM caused by Schizophyllum commune (S. commune), with satisfactory response to treatment with a combination of an inhaled corticosteroid and a long-acting ß 2-agonist. The patient was a 61-year-old man who was referred to our hospital with dry cough and abnormal findings on chest radiography. He had peripheral blood eosinophilia and elevated levels of total serum IgE. High-resolution CT showed multiple areas of patchy consolidation with high-attenuation mucus plugs in the right upper lobe. Bronchoscopy revealed mucus plug impaction in the bronchial lumen, and Grocott's staining of the mucus detected fungal hyphae. Bronchioalveolar lavage fluid culture yielded white woolly colonies, which was subsequently identified as S. commune by MALDI-TOF MS and gene sequencing. Serology was positive for S. commune-specific IgE and IgG. We made a definitive diagnosis of ABPM caused by S. commune. Symptoms and chest CT findings improved considerably with inhaled combined fluticasone furoate/vilanterol trifenatate therapy, without the use of systemic corticosteroids or antifungal agents.

Entrectinib-induced syndrome of inappropriate antidiuretic hormone secretion in a patient with ROS1-rearranged non-small cell lung cancer.

A 75-year-old woman was referred to our hospital because of a productive cough and an abnormal shadow on chest radiography. She was diagnosed as having metastatic lung adenocarcinoma harbouring ROS proto-oncogene 1 (ROS1). First-line therapy was instituted with entrectinib 600 mg daily, and a gradual decrease in serum sodium level was noticed on day 6, which deteriorated to Grade 3 hyponatremia on day 12. Despite a partial therapeutic response to entrectinib, she developed fatigue and dizziness, so the drug was withdrawn. The clinical findings and laboratory workup were compatible with a diagnosis of syndrome of inappropriate antidiuretic hormone secretion (SIADH) due to entrectinib. The hyponatremia subsequently improved and entrectinib was resumed at a reduced dose of 400 mg daily, which has been continued to date, with no recurrence of SIADH.

Comparison of hemodynamics during induction of general anesthesia with remimazolam and target-controlled propofol in middle-aged and elderly patients: a single-center, randomized, controlled trial.

BACKGROUND: Remimazolam confers a lower risk of hypotension than propofol. However, no studies have compared the efficacy of remimazolam and propofol administered using target-controlled infusion (TCI). This study aimed to investigate hemodynamic effects of remimazolam and target-controlled propofol in middle-aged and elderly patients during the induction of anesthesia. METHODS: Forty adults aged 45-80 years with the American Society of Anesthesiologists Physical Status 1-2 were randomly assigned to remimazolam or propofol group (n = 20 each). Patients received either remimazolam (12 mg/kg/h) or propofol (3 µg/mL, TCI), along with remifentanil for inducing anesthesia. We recorded the blood pressure, heart rate (HR), and estimated continuous cardiac output (esCCO) using the pulse wave transit time. The primary outcome was the maximum change in mean arterial pressure (MAP) after induction. Secondary outcomes included changes in HR, cardiac output (CO), and stroke volume (SV). RESULTS: MAP decreased after induction of anesthesia in both groups, without significant differences between the groups (- 41.1 [16.4] mmHg and - 42.8 [10.8] mmHg in remimazolam and propofol groups, respectively; mean difference: 1.7 [95% confidence interval: - 8.2 to 4.9]; p = 0.613). Furthermore, HR, CO, and SV decreased after induction in both groups, without significant differences between the groups. Remimazolam group had significantly shorter time until loss of consciousness than propofol group (1.7 [0.7] min and 3.5 [1.7] min, respectively; p < 0.001). However, MAP, HR, CO, and SV were not significantly different between the groups despite adjusting time until loss of consciousness as a covariate. Seven (35%) and 11 (55%) patients in the remimazolam and propofol groups, respectively, experienced hypotension (MAP < 65 mmHg over 2.5 min), without significant differences between the groups (p = 0.341). CONCLUSIONS: Hemodynamics were not significantly different between remimazolam and target-controlled propofol groups during induction of anesthesia. Thus, not only the choice but also the dose and usage of anesthetics are important for hemodynamic stability while inducing anesthesia. Clinicians should monitor hypotension while inducing anesthesia with remimazolam as well as propofol. TRIAL REGISTRATION: UMIN-CTR (UMIN000045612).

A 52-Year-Old Obese Man With Persistent Cough.

CASE PRESENTATION: A 52-year-old man was referred to our hospital with an abnormal chest radiography infiltrate. He presented with cough that persisted for 1 month without fever, chills, dyspnea, or sputum. He has been treated with clarithromycin 400 mg/d for 1 week with no improvement. He had a history of hypertension, hyperuricemia, and gastroesophageal reflux disease. He had no family history of respiratory disease. He smoked 10 cigarettes daily for 10 years, which he had quit 15 years ago. He denied a history of alcohol or illicit drug use, occupational exposure, recent travel, and exposure to TB. He reported being sexually active with one current partner.

Co-infection with Nocardia spp. in a patient with Mycobacterium avium complex pulmonary disease: A case report.

Mycobacterium avium complex pulmonary disease (MAC-PD) is sometimes accompanied by co-infection with other pathogenic microorganisms such as Pseudomonas aeruginosa and Haemophilus influenzae. However, co-infection with Nocardia spp. has been rarely reported. We report on a patient diagnosed as having co-infection with Nocardia after treatment for MAC-PD, which was successfully treated using trimethoprim-sulfamethoxazole (TMP-SMX). A 74-year-old woman with MAC-PD was admitted to our hospital to undergo re-examination for pathogenic microorganisms because chest computed tomography (CT) findings did not improve after treatment for MAC-PD. She underwent bronchoscopy and Nocardia spp. was detected from bronchoalveolar lavage fluid culture. Chest CT findings improved after 6 months of treatment using TMP-SMX. Co-infection with other pathogenic microorganisms should be considered when chest CT findings worsen after adequate treatment of MAC-PD. Chest CT findings of Nocardia pulmonary disease in immunocompetent patients can mimic those of MAC-PD and should therefore be differentiated one from the other.

Impact of surgical masks on fraction of inspired oxygen during oxygen therapy depends on the type of oxygen masks and respiratory conditions: volunteer- and simulation-based studies.

PURPOSE: We investigated the impact of surgical masks (SM) during oxygen therapy using oxygen masks in volunteer- and simulation-based studies. METHODS: Fifteen volunteers wore the Hudson RCI® or Open-Face Mask® with/without an SM. The fraction of inspired oxygen concentration (FIO2), end-tidal CO2 (EtCO2), partial pressure of inspired CO2 (PICO2), and respiratory rate (RR) were measured. The oxygen flow rate increased from 0 to 10 L/min. In the simulation-based study, FIO2 was measured using a simulator that reproduced spontaneous breathing. RR was 12 or 24 bpm, and the tidal volume (Tv) was 300, 500, or 700 mL. The effect of oxygen mask fitting conditions was also examined. The primary outcome measure was FIO2 at 6 L/min. RESULTS: In the volunteer-based study, FIO2 was reduced when the SM was used with the Hudson RCI® or Open-Face Mask®. The FIO2 drop was larger with the Open-Face Mask® than with the Hudson RCI®. The RR, EtCO2, and PICO2 significantly changed with the SM, but the differences were not clinically meaningful. In the simulation-based study, the SM with the Hudson RCI® did not reduce FIO2, but the SM with the Open-Face Mask® significantly decreased FIO2 under several conditions. However, the SM with the Hudson Mask® reduced FIO2 when the fit of the mask was inadequate. With the Open-Face Mask®, lower RR and Tv resulted in larger differences in FIO2. CONCLUSIONS: The SM decreased FIO2 during oxygen therapy with oxygen masks. The impact of SM depended on the type of the oxygen mask, mask fitting, and respiratory condition.

Desflurane improves lung collapse more than propofol during one-lung ventilation and reduces operation time in lobectomy by video-assisted thoracic surgery: a randomized controlled trial.

BACKGROUND: This study evaluated whether desflurane improved lung collapse during one-lung ventilation (OLV) more than propofol, and whether it could reduce the operation time of video-assisted thoracic surgery. METHODS: Sixty patients undergoing lobectomy by video-assisted thoracic surgery (VATS) were randomly assigned to general anesthesia with desflurane or propofol. Lungs were inspected by thoracoscope at 10, 30, and 60 min after initiation of OLV. After surgery, the Lung Collapse Score, a composite of lung color and volume assessments, was assigned by two clinicians blinded to the anesthetic regimen. The primary outcome was operation time. The secondary outcome included the complication rate. RESULTS: Of the 60 participants, 50 completed the study, 26 in Desflurane group and 24 in Propofol group. The Lung Collapse Scores at 30 and 60 min after OLV initiation were significantly better in Desflurane group than in Propofol group, and operation time was significantly shorter in Desflurane group (214 (57) min vs. 262 (72) min [mean (SD)], difference in means, -48; 95% CI, -85 to -11; P = 0.01). The incidence of multiple complications was 1/26 (3%) and 6/24 (25%) in Desflurane and Propofol group, respectively (relative risk, 0.1; 95% CI, 0.02 to 1.18; P = 0.04). CONCLUSIONS: Desflurane improved lung collapse during OLV and significantly shortened VATS lobectomy operation time compared to propofol in our studied patients. Desflurane resulted in fewer postoperative complications. Thus, desflurane may be an appropriate anesthetic during lobectomy by VATS requiring OLV. TRIAL REGISTRATION: The study was registered with the University Hospital Medical Information Network ( UMIN000009412 ). The date of disclosure of this study information is 27/11/2012. On this date, we registered the study into UMIN; patients were included from 2013 to 2014. However, on 11/27/2015, the UMIN system administrator suggested a detailed description. Thereafter, we added it to the Randomization Unit. Despite being prospective, it was retrospectively registered on UMIN for the above reasons.

The accuracy and clinical impact of the morphological identification of Aspergillus species in the age of cryptic species: A single-centre study.

BACKGROUND: Aspergillus spp. is identified morphologically without antifungal susceptibility tests (ASTs) in most clinical laboratories. The aim of this study was to examine the clinical impact of the morphological identification of Aspergillus spp. to ensure the adequate clinical management of Aspergillus infections. PATIENTS/METHODS: Aspergillus isolates (n = 126) from distinct antifungal treatment-naïve patients with aspergillosis were first identified morphologically, followed by species-level identification via DNA sequencing. An AST for itraconazole (ITC) and voriconazole (VRC) was performed on each Aspergillus isolate. RESULTS: Based on the genetic test results, morphology-based identification was accurate for >95% of the isolates at the species sensu lato level although the test concordance of Aspergillus spp. with low detection rates was low. The rates of cryptic species were found to be 1.2% among the isolates of A. fumigatus complex and 96.8% in the A. niger complex. Cryptic species with lower susceptibilities to antifungal drugs than sensu stricto species among the same Aspergillus section were as follows: The A. lentulus (n = 1) isolates had low susceptibilities to azoles among the A. fumigatus complex species (n = 86), and A. tubingensis isolates (n = 18) exhibited lower susceptibility to azoles among the A. niger complex species (n = 31). CONCLUSION: Diagnostic accuracy was high at the A. fumigatus and A. niger complex level. However, in the presence of cryptic species, a solely morphological identification was insufficient. Particularly, ITC and VRC might be inappropriate for aspergillosis treatment when the A. niger complex is identified morphologically because it is possible that the Aspergillus isolate is A. tubingensis.

Exophiala dermatitidis pneumonia with bronchiectasis required prolonged voriconazole treatment.

Exophiala dermatitidis is a black fungus that rarely causes respiratory infection. We report a case of E. dermatitidis pneumonia with bronchiectasis that relapsed after 11 months of voriconazole (VRCZ) treatment in a rheumatoid arthritis (RA) patient with bronchiectasis. A 65-year-old woman with RA and abnormal findings on chest radiography was referred for assessment of chronic cough and increased sputum production. She underwent bronchoscopy, and E. dermatitidis was identified from bronchoalveolar lavage fluid (BALF). Exophiala dermatitidis chronic lower respiratory tract infection and pneumonia were diagnosed. Although her condition improved after 11 months of VRCZ treatment, chest computed tomography (CT) images showed worsening at five months after the cessation of VRCZ treatment and E. dermatitidis was again detected in BALF. Re-administration of VRCZ for two years improved symptoms and chest CT images, and her condition is currently stable. In patients with bronchiectasis, E. dermatitidis pneumonia might require prolonged antifungal treatment.

Bronchial Brushing and Diagnosis of Pulmonary Nontuberculous Mycobacteria Infection.

BACKGROUND: The optimal bronchoscopy procedure for diagnosis of pulmonary nontuberculous mycobacteria (NTM) infection is unclear. OBJECTIVE: This study investigated the usefulness of bronchial brushing in bronchoscopy for diagnosis of pulmonary NTM infection in patients with suspected NTM lung disease and nodular bronchiectasis on chest computed tomography (CT) images. METHODS: Bronchoscopy was prospectively performed for 69 patients with clinically suspected pulmonary NTM infection on chest CT from December 2017 through December 2019. Before and after bronchial brushing, bronchial washing was performed with 20 or 40 mL of normal sterile saline at the same segmental or subsegmental bronchi. Before and after bronchial brushing, samples of the washing fluid (pre- and postbrushing samples) and brush deposits (brush samples) were obtained and cultured separately. RESULTS: NTM was detected in 37 of the 69 (53.6%) patients (Mycobacterium avium in 27, Mycobacterium intracellulare in 7, M. abscessus in 2, and M. kansasii in 2). NTM was detected in 34 (49.3%) prebrushing samples, in 27 (39.1%) postbrushing samples, and in 20 (29.0%) brush samples from the 69 patients. In 2 (2.9%) patients, NTM was detected only in postbrushing samples; in 1 (1.4%) patient, NTM was detected only in a brush sample. As compared with bronchial washing only, additional bronchial brushing increased the NTM culture-positive rate by 4.3% (3/69). Bronchial brushing caused bleeding, requiring hemostasis in 5 (7.2%) patients. CONCLUSION: Additional bronchial brushing increased the NTM culture-positive rate by only 4.3% (3/69), as compared with bronchial washing alone. Thus, the usefulness of brushing appears to be limited.

Comparison of QuantiFERON-TB Gold Plus, QuantiFERON-TB Gold In-Tube, and T-SPOT.TB among patients with tuberculosis.

OBJECTIVES: This study evaluated the efficacy of the following interferon (IFN)-γ release assays (IGRAs): QuantiFERON-TB Gold Plus (QFT-Plus), QFT-Gold In-Tube (QFT-GIT), and T-SPOT. TB (T-SPOT) with the quantitative values of IFN-γ response. METHODS: Blood samples were collected from patients with active tuberculosis (TB), latent TB infection (LTBI), individuals with previous TB infection, and healthy volunteers enrolled between May 2017 and June 2018. RESULTS: IGRAs results were analyzed in 175 subjects (76 had active TB, 14 had LTBI, 35 had prior TB infection, and 50 were healthy). QFT-Plus and QFT-GIT revealed equal efficacy for IFN-γ values, and the IFN-γ response in QFTs tended to increase with the spot counts in T-SPOT, with similar high sensitivities (approximately 90%) in the active TB group. The test concordance of two of three IGRAs was optimal among all subjects (κ coefficients: 0.82-0.96). Additionally, the median quantitative values of IFN-γ with QFT-Plus and QFT-GIT were higher in the active TB group than in the LTBI and previous TB groups. CONCLUSION: Three IGRAs showed equivalent efficacy with high sensitivities and higher IFN-γ response in active TB group than that in non-active TB group.

Serial change in serum biomarkers during treatment of Non-HIV Pneumocystis pneumonia.

BACKGROUND: For patients with non-human immunodeficiency virus (HIV) Pneumocystis pneumonia (PCP), data are limited on serial changes in serum biomarkers and the correlations with clinical outcomes. OBJECTIVE: This study evaluated serial change in serum biomarkers and clinical outcomes of non-HIV PCP. METHODS: We retrospectively reviewed data from 63 patients treated for non-HIV PCP at Toho University Omori Medical Center. The patients were classified as survivors and nonsurvivors on the basis of 60-day PCP mortality. The groups were compared for clinical course and levels of serum biomarkers (ß-D glucan, Krebs von den Lungen-6 antigen [KL-6], and surfactant protein-D [SP-D]), which were measured at baseline, and 7 days and 14 days after starting treatment. In addition, serial changes in serum biomarkers were analyzed in survivors and nonsurvivors. RESULTS: There were 14 PCP nonsurvivors and 49 survivors. Biomarker values were not different between groups at baseline. At 7 and 14 days after starting treatment, the proportions of patients with elevated ß-D glucan and KL-6 did not significantly differ between groups; however, the proportion of patients with elevated SP-D was significantly lower among survivors than among nonsurvivors (57.1% vs. 100%, p = 0.009; 30% vs. 100%, p < 0.001; respectively). SP-D on day 14 was significantly lower than that at baseline among survivors (99.6 [61.0-190.3] vs. 156 [100.8-283.5]; p = 0.045) but significantly higher among nonsurvivors (974 [744.5-1565] vs. 317 [211-448]; p = 0.03). CONCLUSION: Serum SP-D value continues to increase after failure of treatment for non-HIV PCP and may thus be associated with outcomes for non-HIV PCP patients.