[PROBLEMS ASSOCIATED WITH THE DIAGNOSIS OF PROLONGED/CHRONIC COUGH IN CLINICAL SETTINGS].

BACKGROUND: Many patients visit primary care clinics or local hospitals with a complaint of prolonged/chronic cough. Among the different types of chronic cough, cough variant asthma (CVA) and postinfectious cough may be the most common types, and their differential diagnosis is difficult. Some physicians tend to prescribe inhaled corticosteroids before establishing a definitive diagnosis. METHODS: We retrospectively investigated useful findings for diagnosis in 77 patients with a complaint of prolonged/ chronic cough to detect meaningful findings for differential diagnosis and to identify problems associated with diagnosis in clinical practice. RESULTS: CVA was diagnosed in 39 patients, and postinfectious cough was diagnosed in 19. Compared with postinfectious cough, CVA was associated with significant characteristics such as "diurnal variation of symptoms," "response to inhalation of short acting ß2 agonist (SABA)," and "recurrent episodes of symptoms." CVA was associated with high FeNO levels as well, and high FeNO levels were specific to CVA. However, these useful characteristics were not significant in the patients who had been prescribed ICS before visiting our hospital. CONCLUSIONS: Medical examination and determination of FeNO levels are useful for the differential diagnosis of prolonged/chronic cough, before treatment with ICS.

Overexpression of microRNA-155 suppresses chemokine expression induced by Interleukin-13 in BEAS-2B human bronchial epithelial cells.

BACKGROUND: MicroRNAs are non-coding small RNAs that regulate expression of target genes by binding to 3' untranslated regions. In this study, we used bronchial epithelial cells to investigate in vitro the role of the microRNA miR-155 in the expression of chemokines associated with airway inflammation. miR-155 has previously been reported to regulate allergic inflammation. METHODS: BEAS-2B bronchial epithelial cells were cultured and transfected with mimic or inhibitor oligonucleotides to overexpress or downregulate miR-155, as confirmed by real-time PCR. Cells were then stimulated with tumor necrosis factor-alpha, interleukin-13 (IL-13), and a double stranded RNA that binds Toll-like receptor 3. Expression and secretion of the chemokines CCL5, CCL11, CCL26, CXCL8, and CXCL10 were then quantified by real-time PCR and ELISA, respectively. Phosphorylation of signal transducer and activator of transcription 6 (STAT6), a target of the IL-13 receptor, was analyzed by ELISA. RESULTS: miR-155 overexpression significantly suppressed IL-13-induced secretion of CCL11 and CCL26. These effects were specific, and were not observed for other chemokines, nor in cells with downregulated miR-155. miR-155 overexpression also suppressed CCL11 and CCL26 mRNA, but did not affect expression of the IL-13 receptor or phosphorylation of STAT6. CONCLUSIONS: miR-155 specifically inhibits IL-13-induced expression of eosinophilic chemokines CCL11 and CCL26 in bronchial epithelial cells, even though the 3'-untranslated region of these genes do not contain a consensus binding site for miR-155.

Clinical features and outcomes of aspiration pneumonia compared with non-aspiration pneumonia: a retrospective cohort study.

Pneumonia is a leading cause of death among elderly patients. Although aspiration pneumonia (AP) commonly occurs with aging, its clinical features and outcomes are still uncertain. The aims of this study were to describe the clinical features and outcomes of AP and to assess whether presence of AP affects clinical outcomes in patients with community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP). We retrospectively analyzed patients with CAP and HCAP hospitalized in our institution in Japan from October 2010 to March 2012. We compared clinical features and outcomes between AP and non-AP, and investigated risk factors for recurrence of pneumonia and death. Of 214 consecutive patients, 100 (46.7%) were diagnosed as having aspiration pneumonia. These patients were older and had lower body mass index, more comorbidities, and poorer Eastern Cooperative Oncology Group performance status (ECOG PS) than the patients with non-AP. Patients with AP had more severe disease, required longer hospital stays, and had a frequent recurrence rate of pneumonia and higher mortality. In multivariate analyses, AP, age, and ECOG PS were related to recurrence of pneumonia, and the prognostic factors were CURB-65 score and ECOG PS. AP was not a significant indicator for prognosis but was the strongest risk factor for recurrence of pneumonia. Clinical background and outcomes including recurrence and mortality of AP were obviously different from those of non-AP; therefore AP should be considered as a distinct subtype of pneumonia, and it is important to prevent the recurrence of pneumonia in the patients with AP.

Detection of metallo-ß-lactamase genes in clinically isolated Klebsiella pneumoniae and Klebsiella oxytoca.

We detected and characterized metallo-ß-lactamase genes (blaIMP-1 and blaIMP-11) in third generation cephalosporin-resistant Klebsiella pneumoniae and Klebsiella oxytoca isolated at Showa University Hospital between January 1, 2011 and December 31, 2012. The cephalosporin-resistant K pneumoniae strains were frequently isolated from the urine, while one strain of K. pneumoniae, which was resistant to carbapenem, was isolated from the stool. We analyzed the phenotypes and genotypes of the metallo-ß-lactamase genes from the 16 strains of cephalosporin-resistant-K pneumoniae and 6 strains of -K. oxytoca isolated from the same ward. The minimum inhibitory concentrations of imipenem were below 4 µg/ml in 21 out of the 22 isolated strains. The double disc synergy test using ceftazidime and sodium mercaptoacetic acid revealed enlargements in the inhibitory zones of 14 of the 16 strains of K. pneumoniae and all 6 strains of K. oxytoca. Metallo-ß-lactamase genes were detected in all of the tested strains, with blaIMP-1 in 3 K. pneumoniae and 1 K. oxytoca, blaIMP-11 in 13 K pneumoniae and 4 K. oxytoca, and both blaIMP-1 and blaIMP-11 in one K. oxytoca. Our results indicate that third generation cephalosporin-resistant and imipenem-susceptible K. pneumoniae and K. oxytoca possess the metallo-ß-lactamase gene. The active surveillance of metallo-ß-lactamase genes should be performed in clinical laboratories. (Original).

Combination of anti-glycopeptidolipid-core IgA antibody and clinical features for diagnosing potential nontuberculous mycobacterium pulmonary disease in routine practice.

BACKGROUND: The anti-Mycobacterium avium complex (MAC) antibody test measures levels of IgA antibody against the glycopeptidolipid (GPL) core in the bacterial cell walls and is a useful clinical indicator of nontuberculous mycobacterium pulmonary disease (NTM-PD). However, it is not currently possible to diagnose the disease using anti-MAC antibodies alone. OBJECTIVES: The study aim was to assess the efficacy of the combination of anti-MAC antibodies and clinical findings for diagnosing potential NTM-PD. METHODS: This cross-sectional study included 938 patients tested using the anti-MAC antibody. NTM-PD was diagnosed by multiple positive cultures of the same species in sputum samples. Multivariate logistic regression models were used to identify the clinical factors related to NTM-PD. RESULTS: Overall, 19.6% (184/938) of participants were diagnosed with NTM-PD. In multivariate analysis, positive anti-MAC antibodies, low body mass index, absence of malignancy, and cavity-forming lung lesions were significantly associated with NTM-PD at diagnosis. The positive rates of the anti-MAC antibody test were 79.4% (135/170) for MAC and 55.6% (5/9) for Mycobacterium abscessus complex, respectively. CONCLUSIONS: Bronchoscopic examinations should be performed especially in certain types of individuals from whom sputum samples cannot be obtained. Anti-MAC antibodies are also positive in patients other than those harboring MAC, but the rate may be low because of the different components in GPLs.

Improvement in activities of daily living and exercise tolerance in a patient with severe COVID-19 and femoral nerve palsy after Kaifukuki rehabilitation: a case report.

Yashiro T, Wada Y, Sugiyama M, Tateno H, Kasai F, Kawate N. Improvement in activities of daily living and exercise tolerance in a patient with severe COVID-19 and femoral nerve palsy after Kaifukuki rehabilitation: a case report. Jpn J Compr Rehabil Sci 2021; 12: 53-57. Introduction: There have been many reports on rehabilitation techniques for patients with coronavirus disease 2019 (COVID-19). However, few have reported on the use of Kaifukuki rehabilitation for severe COVID-19 cases with complications of femoral nerve palsy after veno-venous extracorporeal membrane oxygenation (VV-ECMO) management. Case: A male in his 50s who underwent VV-ECMO management during the course of his treatment for COVID-19 developed femoral nerve palsy due to iliopsoas hematoma. From day 120 after admission, he underwent Kaifukuki rehabilitation focusing on exercise therapy, activities of daily living (ADL) training, and respiratory rehabilitation to improve ADL and exercise tolerance. His respiratory function, functional independence measure scores, and 6-min walk test results improved. The patient was discharged on day 196. His recovery progressed without any further deterioration. Discussion: Kaifukuki rehabilitation, focusing on respiratory rehabilitation, contributed to the improvement of ADL and exercise tolerance in a patient with severe COVID-19. In addition, attention should be paid to femoral nerve palsy after VV-ECMO.

Impact of the interferon-γ release assay and glomerular filtration rate on the estimation of active tuberculosis risk before bronchoscopic examinations: a retrospective pilot study.

BACKGROUND: Bronchoscopic examinations are vital to diagnose pulmonary diseases. However, as coughing is triggered during and after the procedure, it is imperative to take measures against nosocomial infections, especially for airborne infections like tuberculosis (TB). The interferon-γ release assay (IGRA) has recently been established as a method to evaluate the infection status of TB. We aimed to ascertain the efficacy of IGRA and clinical findings in estimating the prevalence of active TB before bronchoscopy. METHODS: We obtained IGRA results from 136 inpatients using a QuantiFERON-TB Gold In-Tube test. Bronchoscopy samples were cultured in Mycobacteria Growth indicator tubes and 2% Ogawa solid medium. We evaluated the adjusted effects of multiple clinical variables on active TB status using a logistic regression model. In addition, multiple variables were converted into a decision tree to predict active TB. RESULTS: Five (3.7%) patients were diagnosed with culture-positive TB, two of whom were simultaneously diagnosed with non-small-cell lung carcinoma or small-cell lung carcinoma. The multivariate analysis suggested the probability of predicting active TB using the IGRA [odds ratio (OR), 72.7; 95% confidence interval (CI), 3.169-1668; P=0.007] and decreased estimated glomerular filtration rate (eGFR) (OR, 0.937; 95% CI, 0.882-0.996; P=0.038) in patients undergoing bronchoscopy. A decision tree validated the use of these two variables to predict active TB. CONCLUSIONS: IGRA test results are useful for predicting active TB before bronchoscopy. This strategy could identify patients who require antibiotic therapy to prevent TB or who are in the active phase of TB.

Acquired resistance L747S mutation in an epidermal growth factor receptor-tyrosine kinase inhibitor-naïve patient: A report of three cases.

The purpose of the present study was to report cases of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-naïve patients carrying a mutation associated with acquired resistance to the drug. Gene alterations in 77 lung carcinoma patients were analyzed by collecting and studying curette lavage fluid at the time of diagnosis. PCRs were performed to amplify mutation hotspot regions in EGFR genes. The PCR products were direct-sequenced and the mutations confirmed by resequencing using different primers. Case 1 was a 78-year-old Japanese male diagnosed with stage IB lung adenocarcinoma who was found to have two EGFR mutations, G719S and L747S. Case 2 was a 73-year-old Japanese male diagnosed with stage IV squamous cell lung carcinoma and bone metastasis who had the EGFR mutation, L747S. Case 3 was an 82-year-old Japanese male diagnosed with hyponatremia due to inappropriate secretion of antidiuretic hormone and stage IIIB small cell lung carcinoma (SCLC) who had the EGFR mutation, L747S. Thus, the EGFR mutation L747S associated with acquired EGFR-TKI resistance was detected in two non-small cell lung carcinoma (NSCLC) patients and one SCLC patient, none of whom had ever received EGFR-TKI. The patients were current smokers with stages at diagnosis ranging from IB to IV, and their initial tumors contained resistant clones carrying L747S. L747S may be associated with primary resistance. To the best of our knowledge, this study is the first report of an EGFR mutation associated with resistance to EGFR-TKI in SCLC patients. The early detection of EGFR-TKI resistance mutations may be beneficial in making treatment decisions for lung carcinoma patients, including those with SCLC.

Analysis of EGFR, KRAS and P53 mutations in lung cancer using cells in the curette lavage fluid obtained by bronchoscopy.

Histopathological samples are commonly used for molecular testing to detect both oncogenes and tumor-suppressor genes in lung cancer. The purpose of this study was to determine the efficacy of using curette lavage fluid for molecular testing to detect EGFR, KRAS and P53 mutations in lung cancer patients. Samples were obtained from 77 lung cancer patients by bronchoscopy at the time of diagnosis, collected by scraping the site of the primary tumor lesion with a curette. DNA was extracted from cells in the curette lavage fluid, and PCRs were performed to amplify mutation hot spot regions in the EGFR, KRAS and P53 genes. The PCR products were direct-sequenced to detect mutations of each gene. The reference sequence of each gene was obtained from GenBank. Overall, 27% (21 of 77) were found with EGFR mutations, 1% (1 of 77) with KRAS mutations, and 36% (28 of 77) with P53 mutations. KRAS mutations were not detected in patients harboring mutations in either EGFR or P53. P53 mutations were identified in 38% (8 of 21) of the patients with EGFR mutations, all of who had advanced lung cancer. Of these patients, a 62-year-old female current smoker was given EGFR-TKI as third-line therapy, with no improvement in clinical symptoms or results of radiographic examination. Multivariate analysis indicated that P53 mutation rates in advanced-stage lung cancer were significantly higher than those in early-stage lung cancer (P=.017). In contrast, EGFR mutation rates were not significantly associated with staging. L747S in EGFR, described as a mutation associated with secondary resistance to EGFR-TKI, was detected in three patients who had never received EGFR-TKI, including one SCLC patient. It is possible to analyze EGFR, KRAS and P53 mutations using curette lavage fluid collected from lung cancer patients. This is useful when sufficient amounts of tumor samples cannot be obtained. Data from the current study suggest that EGFR mutations in concert with P53 mutations accelerate cancer development and lead to evolution of therapeutic resistance.

Azacitidine-induced pneumonitis in a patient with myelodysplastic syndrome: first case report in Japan.

A 74-year-old Japanese man with myelodysplastic syndrome (MDS) received chemotherapy with azacitidine. From the second day after starting the administration, he complained of fever, cough and shortness of breath. Chest roentgenography and computed tomography showed consolidations and ground-glass opacities. His symptoms grew from worse to life-threatening. We diagnosed him with azacitidine-induced pneumonitis and began administering corticosteroids. Thereafter, his symptoms and radiographic abnormalities improved. Azacitidine is a hypomethylating agent that improves the survival of MDS patients. Although this drug is commonly well tolerated and rarely causes severe lung injury, it is important to consider the potentially serious adverse effects of azacitidine-induced pneumonitis.