Relationship between oral health and prognosis in patients with empyema: Single center retrospective study with propensity score matching analysis.

BACKGROUND: Empyema is a life-threatening infection often caused by oral microbiota. To the best of our knowledge, no reports have investigated the association between the objective assessment of oral health and prognosis in patients with empyema. MATERIALS AND METHODS: A total of 63 patients with empyema who required hospitalization at a single institution were included in this retrospective study. We compared non-survivors and survivors to assess risk factors for death at three months, including the Renal, age, pus, infection, diet (RAPID) score, and Oral Health Assessment Tool (OHAT) score. Furthermore, to minimize the background bias of the OHAT high-score and low-score groups determined based on the cut-off value, we also analyzed the association between the OHAT score and death at 3 months using the propensity score matching method. RESULTS: The 3-month mortality rate was 20.6% (13 patients). Multivariate analysis showed that a RAPID score ≥5 points (odds ratio (OR) 8.74) and an OHAT score ≥7 points (OR 13.91) were significantly associated with death at 3 months. In the propensity score analysis, a significant association was found between a high OHAT score (≥7 points) and death at 3 months (P = 0.019). CONCLUSION: Our results indicated that oral health assessed using the OHAT score may be a potential independent prognostic factor in patients with empyema. Similar to the RAPID score, the OHAT score may become an important indicator for the treatment of empyema.

Usefulness Analysis of Fraction of Exhaled Nitric Oxide for the Differential Diagnosis of Acute Cough.

BACKGROUND/AIM: Measuring the fraction of exhaled nitric oxide (FeNO) is useful in the diagnosis of asthma and cough variant asthma. The aim of this study was to clarify the significance of measuring the FeNO in the differential diagnosis of acute cough. PATIENTS AND METHODS: We analyzed 80 patients who visited the clinic with the chief complaint of acute cough having experienced an asthma-like episode from January 2014 to July 2015. RESULTS: Infectious cough alone was present in 21% of patients, while 30% had asthmatic cough alone and 49% had a combination of infectious and asthmatic cough. The values of FeNO in those with asthmatic cough (30.4±24.7 ppb) and asthmatic/infectious cough (33.2±17.4 ppb) were significantly higher than those with just infectious cough (13.7±3.2 ppb) (p=0.0089 and p<0.0001, respectively). CONCLUSION: FeNO measurement is useful for distinguishing asthmatic diseases, even in the differential diagnosis of acute cough.

Analysis of nocturnal desaturation waveforms using algorithms in patients with idiopathic pulmonary fibrosis.

PURPOSE: Sleep-disordered breathing is recognized as a comorbidity in patients with idiopathic pulmonary fibrosis (IPF). Among them, nocturnal hypoxemia has been reported to be associated with poor prognosis and disease progression. We developed a diagnostic algorithm to classify nocturnal desaturation from percutaneous oxygen saturation (SpO2) waveform patterns: sustained pattern, periodic pattern, and intermittent pattern. We then investigated the prevalence of nocturnal desaturation and the association between the waveform patterns of nocturnal desaturation and clinical findings of patients with IPF. METHODS: We prospectively enrolled patients with IPF from seven general hospitals between April 2017 and March 2020 and measured nocturnal SpO2 and nasal airflow by using a home sleep apnea test. An algorithm was used to classify the types of nocturnal desaturation. We evaluated the association between sleep or clinical parameters and each waveform pattern of nocturnal desaturation. RESULTS: Among 60 patients (47 men) who met the eligibility criteria, there were 3 cases with the sustained pattern, 49 cases with the periodic pattern, and 41 cases with the intermittent pattern. Lowest SpO2 during sleep and total sleep time spent with SpO2 < 90% were associated with the sustained pattern, and apnea-hypopnea index was associated with the intermittent pattern. CONCLUSION: We demonstrated the prevalence of each waveform and association between each waveform and sleep parameters in patients with IPF. This classification algorithm may be useful to predict the degree of hypoxemia or the complication of obstructive sleep apnea.

Validity of a novel respiratory rate monitor comprising stretchable strain sensors during a 6-min walking test in patients with chronic pulmonary obstructive disease.

BACKGROUND: Breathing frequency is rarely measured during a field walking test since the current monitoring system using a face mask is cumbersome for older adults. For effective clinical application, we aimed to validate the new respiratory monitor using wearable strain sensors during a 6-min walk test (6MWT) in young adults and patients with chronic obstructive pulmonary disease (COPD). METHODS: The study included young adults and patients with stable COPD voluntarily recruited from three hospitals. Breathing frequency during 6MWT were measured by the strain sensor and a nasal capnometer. Total breathing frequencies were measured by the capnometer. The Bland-Altman method was used to estimate the mean limit of agreement for breathing frequency. RESULTS: A total of 23 young adults (age = 23.1 ± 3.7, mean ± SD) and 50 patients with COPD (age = 75.2 ± 7.2, %FEV1 = 59.1 ± 19.7) were analyzed. During the entire test period, the total breathing frequencies were measured based on an average of 252 ± 46 breaths, and the total breathing frequency was higher in patients with COPD than in young adults (mean difference = -3.349, p < 0.0013). The mean difference in breathing frequency between the strain sensors and capnometer was -0.28 (95%CI: 0.75 to 0.20), and the limit of agreement ranged from -4.1 to 3.6. The CI of the limit of agreement included the limit of equivalence (4 counts/min). CONCLUSIONS: The novel respiratory monitor with wearable sensors achieved the target accuracy in both young adults and patients with COPD in the 6MWT.

Prospective Study of Nocturnal Desaturation in Patients Receiving Home Oxygen Therapy.

Objective Nocturnal desaturation is common in patients with chronic respiratory disease and often worsens the prognosis. Therefore, it should be diagnosed accurately and appropriately treated. The aim of this study was to clarify the diversity of nocturnal desaturation. Methods We prospectively enrolled 58 outpatients diagnosed with chronic respiratory disease receiving home oxygen therapy and measured nocturnal SpO2 using a portable oximeter. We classified nocturnal desaturation (3% decrease in SpO2 from baseline) into three patterns: periodic pattern (desaturation duration of <655 seconds), sustained pattern (desaturation duration of ≥655 seconds), and intermittent pattern (desaturation and recovery of SpO2 repeated with a cycle of several minutes). Results Nocturnal hypoxemia (SpO2≤88% for more than 5 minutes) was found in 23.8% of patients. The percentage of patients with chronic obstructive pulmonary disease (COPD) was significantly higher in the nocturnal hypoxemia group than in the non-hypoxemia group (80% vs. 40.6%, p=0.03). Desaturation with a periodic pattern was found in 81% of patients, desaturation with a sustained pattern was found in 40.5% of patients, and desaturation with an intermittent pattern was found in 59.5% of patients. In patients with COPD, desaturation with a periodic pattern was found in 85.7%, desaturation with a sustained pattern was found in 47.6%, and desaturation with an intermittent pattern was found in 57.1%. Conclusion The SpO2 waveform of nocturnal hypoxemia was able to be classified into three patterns. Suitable treatment for each pattern might improve the prognosis of these patients.

Characteristics of the nocturnal desaturation waveform pattern of SpO2 in COPD patients: an observational study.

BACKGROUND: Nocturnal desaturation is common in patients with chronic obstructive pulmonary disease (COPD) and impacts disease exacerbation and prognosis. In our previous study, we developed a diagnostic algorithm to classify nocturnal desaturation from SpO2 waveform patterns based on data from patients receiving home oxygen therapy. In this study, we aimed to investigate nocturnal desaturation in patients with COPD based on SpO2 waveform patterns and the associations between the waveforms and clinical data. METHODS: We investigated patients diagnosed with COPD and measured SpO2 and nasal airflow with a type 4 portable long-term recordable pulse oximeter. Then, we classified the SpO2 waveforms with the algorithm and compared the clinical data. RESULTS: One hundred fifty-three patients (136 male and 17 female) were analysed. One hundred twenty-eight of the 153 (83.7%) patients had nocturnal desaturation, with an intermittent pattern (70.6%), sustained pattern (13.1%) and periodic pattern (68.0%). Intriguingly, desaturation with an intermittent pattern was associated with the apnoea-hypopnea index obtained with the portable monitor, and desaturation with a sustained pattern was associated with the cumulative percentage of time at a SpO2 below 90%. CONCLUSIONS: We found that nocturnal desaturation was frequently observed in patients with COPD and could be classified into 3 types of waveform patterns.

A Cross-sectional Survey of the Clinical Manifestations and Underlying Illness of Cough.

AIM: The aim of this study was to identify factors affecting the final diagnosis of cough. MATERIALS AND METHODS: This study recruited 463 consecutive patients who visited five Japanese general hospitals due to cough from October 2006 to September 2007. Of these, 418 patients (90%) who completed a questionnaire designed to acquire data regarding clinical manifestations of cough were included. RESULTS: Most patients with bronchial asthma had cough with seasonal variation and wheezing. Patients with gastro esophageal reflux disease suffered from heartburn and cough without daily or seasonal variation. Cough associated with sinobronchial syndrome was only observed in females and was linked to increased sputum. Patients with whooping cough were bothered by cough interrupting sleep and talking. Patients with cardiogenic cough had exertional dyspnea. CONCLUSION: The specific items on our questionnaire relating to patient characteristics, complications, and triggers of cough, represent useful tools for diagnosing the primary disease producing cough.

An Open-Label, Multi-Institutional, Randomized Study to Evaluate the Additive Effect of a Leukotriene Receptor Antagonist on Cough Score in Patients with Cough-Variant Asthma Being Treated with Inhaled Corticosteroids.

Cough-variant asthma is one of the most common reasons for chronic cough. It is important to treat appropriately cough-variant asthma because 30% to 40% of cough-variant asthma becomes a typical asthma. However, little is known about the treatment of cough-variant asthma except for inhaled corticosteroid (ICS). The aim of this study was to validate the additive efficacy of a leukotriene receptor antagonist (LTRA) on cough score and respiratory function in patients with cough-variant asthma being treated with ICS. A total 28 patients were randomly assigned to either an ICS + LTRA group or an ICS group. There were statistically significant improvements in cough scores in the ICS + LTRA group from 0 weeks (6.7 ± 4.4) to 2 weeks (2.9 ± 3.2) (P < 0.05), 4 weeks (0.7 ± 1.1) (P < 0.001), and 8 weeks (0.8 ± 1.2) (P < 0.001). However similar improvements were not evident in the ICS group from 0 weeks (6.7 ± 4.4) to 2 weeks (5.6 ± 10.0) (P = 0.59), 4 weeks (4.6 ± 7.6) (P = 0.32), and 8 weeks (2.9 ± 5.2) (P = 0.08). On the other hand, no significant changes were evident in the forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC). In conclusion, the LTRA was useful in improving cough in patients with cough-variant asthma, even though it appeared to be ineffective in improving respiratory function.

A case of granulomatosis with polyangiitis (Wegener's granulomatosis) presenting with marked inflamed tracheobronchial mucosa.

A 70-year-old man was admitted to our hospital because of weight loss and persistent dry cough. Chest radiograph and CT showed multiple infiltrates in the bilateral upper lobes and the remarkably thickened bronchial walls. Bronchoscopy revealed diffuse erythema and edema of the tracheobronchial mucosa without any ulcerous legions. Serum MPO-ANCA was positive (155 EU). Transbronchial biopsy was performed and revealed necrotic granulomas with multinucleated giant cells in the bronchial/bronchiolar and parenchymal lesions. Thus, we diagnosed it as a localized form of granulomatosis with polyangiitis (GPA, Wegener's granulomatosis). After treatment with corticosteroid and cyclophosphamide, the bronchial findings were entirely resolved. We report here a rare case of GPA presenting with markedly inflamed tracheobronchial mucosa.

Antithyroid drug-induced agranulocytosis complicated by pneumococcal sepsis and upper airway obstruction.

Streptococcus pneumoniae is a rare pathogen of sepsis in patients with antithyroid drug-induced agranulocytosis. We herein describe a case of antithyroid drug-induced agranulocytosis complicated by pneumococcal sepsis and upper airway obstruction. A 27-year-old woman who was previously prescribed methimazole for nine months presented with a four-day history of a sore throat. She nearly choked and was diagnosed with febrile agranulocytosis. She was successfully treated with intubation, intravenous antibiotics and granulocyte colony-stimulating factor. Her blood cultures yielded S. pneumoniae. Emergency airway management, treatment of sepsis and the administration of granulocyte colony-stimulating factor can improve the clinical course of antithyroid drug-induced pneumococcal sepsis in patients with airway obstruction.

Evaluation of simple aspiration therapy in the initial treatment for primary spontaneous pneumothorax.

OBJECTIVE: A retrospective evaluation of the effectiveness of simple aspiration therapy in primary spontaneous pneumothorax was carried out. METHODS: We enrolled 143 patients with mild and moderate primary spontaneous pneumothorax between June 2006 and October 2010. Clinical backgrounds and therapeutic results from 92 patients that underwent simple aspiration therapy were assessed. RESULTS: All patients were treated safely without any serious complications. With the exception of one patient with an unknown result, the initial success rate after three days was 72.5% (66 out of 91 patients). Chest X-ray analysis at the first medical examination showed that the success rate was significantly low in patients with a larger vertical rim between the apex and top of the lung and a higher collapsed area ratio; in particular, the success rate was markedly decreased in cases that exceeded 8 cm and 50%, respectively. No significant difference was observed in the aspiration volume, however, the success rate was lower when the aspiration volume was more than 1,500 mL. The recurrence rate at one year was 36.4% (24 out of 66 successfully treated patients). CONCLUSION: Our results are nearly identical to previous reports from other countries and show that simple aspiration has proved to be a safe and effective therapy.

[A case of 2009 influenza A (H1N1) virus-associated pneumonia diagnosed from bronchoalveolar lavage specimen].

A 41-year-old man admitted for fever and respiratory failure had visited a local clinic 8 days earlier for fever and cough. Several days earlier, his 3 children had been diagnosed with influenza A by rapid influenza diagnostic test (RIDT) by nasopharyngeal swabs. At the clinic, RIDT done by nasopharyngeal swab two times on two consecutive days had negative results. On admission, chest computed tomography (CT) showed bilateral subpleural and peribronchovascular opacity, although RIDT by nasopharyngeal swab was negative. His respiratory distress worsened rapidly over the next several hours, necessitating intubation. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) with nasopharyngeal secretion was also negative. Despite test results, 2009 influenza A (H1N1) was strongly suspected due to chest CT and history. Oseltamivir was administered and respiratory distress gradually disappeared. He was extubated on hospital day 7. Bronchoalveolar-lavage collected on admission and sent to the laboratory for RT-PCR on hospital day 8, from which the result was positive for influenza A. He was discharged on hospital day 22.

Sphingosine kinase 1 regulates mucin production via ERK phosphorylation.

Our previous report showed that inhibition of sphingosine kinase (SphK) ameliorates eosinophilic inflammation and mucin production in a mouse asthmatic model. To clarify the role of SphK in airway mucin production, we utilized the mouse asthmatic model and found that both SphK and MUC5AC expression were increased and co-localized in airway epithelium. Next we cultured normal human bronchial epithelial cells in an air-liquid interface and treated with IL-13 to induce their differentiation into goblet cells. We found that SphK1 and MUC5AC expression was increased by IL-13 treatment at both protein and mRNA levels, whereas SphK2 expression was not changed. N,N-dimethylsphingosine (DMS), a potent SphK inhibitor, decreased MUC5AC expression up-regulated by IL-13 treatment. Furthermore, DMS inhibited IL-13-induced ERK1/2 phosphorylation but neither p38 MAPK nor STAT6 phosphorylation. These results suggest that SphK1 is involved in MUC5AC production induced by IL-13 upstream of ERK1/2 phosphorylation, and independent of STAT6 phosphorylation.

Targeted inactivation of endothelial lipase attenuates lung allergic inflammation through raising plasma HDL level and inhibiting eosinophil infiltration.

Endothelial lipase (EL) is a novel phospholipase that determines plasma high-density lipoprotein cholesterol (HDL-C) levels. We have investigated the role of HDL-C in lung allergic inflammation by using EL knockout (EL-KO) mice that are high in HDL-C. EL-KO and wild-type control mice were sensitized and challenged with ovalbumin to evoke eosinophilic inflammation in the lung. EL was expressed in epithelial cells, alveolar type II cells, and endothelial cells in the lung, and its expression was upregulated during inflammation. Concomitant with attenuated hyperresponsiveness of the airway smooth muscles, the number of eosinophils in bronchoalveolar lavage and the expression of VCAM-1 were lower in EL-KO mice than in control mice. HDL reduced cytokine-induced VCAM-1 expression in cultured endothelial cells. When plasma HDL levels were decreased to similar levels in both mouse groups by adenovirus-mediated overexpression of EL, however, eosinophil infiltration was still lower in EL-KO mice. In vitro adhesion assays revealed that EL expression on the cell surface promoted the interaction of eosinophils through the ligand-binding function of EL. In summary, targeted inactivation of EL attenuated allergic inflammation in the lung, and the protective effects in EL-KO mice were associated with high plasma HDL levels, downregulation of VCAM-1, and loss of the direct ligand-binding function of EL. Thus EL is a novel modulator of the progression of allergic asthma.

Inhalation of urokinase-type plasminogen activator reduces airway remodeling in a murine asthma model.

The airway remodeling that occurs in asthma is characterized by an excess of extracellular matrix deposition in the submucosa, hyperplasia/hypertrophy of smooth muscle, goblet cell metaplasia, and accumulation of fibroblasts/myofibroblasts. The urokinase-type plasminogen activator (uPA)/plasmin system participates in pericellular proteolysis and is capable of directly degrading matrix components, activating latent proteinases, and activating growth factors. In a mouse ovalbumin (OVA) asthma model, we increased plasminogen activator activity in the lung by administering exogenous uPA or by using mice genetically deficient in the uPA inhibitor plasminogen activator inhibitor-1 (PAI-1) to assess the role of this system in asthma pathogenesis. After intraperitoneal OVA sensitization, mice inhaled OVA plus uPA (500 IU/mouse) or saline by ultrasonic nebulization for 3 wk. When studied 24 h after the final exposure, the groups with upregulated plasmin activity had significantly reduced subepithelial fibrosis within the airway walls and had decreased airway hyperresponsiveness (AHR) to methacholine. Morphometric analysis showed that subepithelial wall thickening of the bronchi (subepithelial area ratio) was also reduced, as were collagen and alpha-smooth muscle actin. Upregulation of plasmin activity also increased the level of hepatocyte growth factor activity in bronchoalveolar lavage fluid, whereas the release of transforming growth factor-beta was decreased. The administration of uPA 1 wk after the last OVA inhalation also significantly reduced lung hydroxyproline content and AHR. These results show that enhancing uPA/plasmin activity lessens the airway remodeling in a murine asthma model.

Rad9 is upregulated and plays protective roles in an acute lung injury model.

The Rad9-Hus1-Rad1 protein complex is believed to respond to DNA damage and play important roles in the cell cycle. We studied the role of Rad9 protein in alveolar epithelial cells in the pathogenesis of acute lung injury. In a mouse model of lung injury induced by bleomycin or lipopolysaccharide, Rad9 expression is increased in type II alveolar epithelial cells from the early stage of lung injury. A549 cells and mouse primary alveolar epithelial cells also upregulated Rad9 expression after exposure to bleomycin. Gene silencing of Rad9 using siRNA decreased the G2/M arrest in A549 cells induced by bleomycin and also decreased the survival of A549 cells following exposure to bleomycin and hydrogen peroxide. In conclusion, Rad9 is a signal in the earlier stage of epithelial cell cycle regulation and plays protective roles in alveolar epithelial cells in the pathogenesis of acute lung injury.

Diffuse periairway thickening in patients with Mikulicz disease.

A 70-year-old woman presented with dry mouth, bilateral swelling of the eyelids, and abnormal taste and smell sensations that had persisted for 3 years. She was diagnosed with Mikulicz disease and presented with dyspnea on exertion afterwards. Chest computed tomography and magnetic resonance imaging showed wall thickening of the trachea and bilateral bronchus. Transbronchial needle aspiration showed lymphoproliferative lesion in the tracheobronchus. The patient was treated with corticosteroid, which improved all of her clinical symptoms, computed tomography, and magnetic resonance findings. In this case, we presented a rare condition of coexistent Mikulicz disease with tracheobroncial wall thickening caused by lymphoproliferation without lesions in small airways or lung.

Inhalation of sphingosine kinase inhibitor attenuates airway inflammation in asthmatic mouse model.

Sphingosine 1-phosphate (S1P) produced by sphingosine kinase (SPHK) is implicated in acute immunoresponses, however, mechanisms of SPHK/S1P signaling in the pathogenesis of bronchial asthma are poorly understood. In this study, we hypothesized that SPHK inhibition could ameliorate lung inflammation in ovalbumin (OVA)-challenged mouse lungs. Six- to eight-week-old C57BL/6J mice were sensitized and exposed to OVA for 3 consecutive days. Twenty-four hours later, mice lungs and bronchoalveolar lavage (BAL) fluid were analyzed. For an inhibitory effect, either of the two different SPHK inhibitors, N,N-dimethylsphingosine (DMS) or SPHK inhibitor [SK-I; 2-(p-hydroxyanilino)-4-(p-chlorophenyl) thiazole], was nebulized for 30 min before OVA inhalation. OVA inhalation caused S1P release into BAL fluid and high expression of SPHK1 around bronchial epithelial walls and inflammatory areas. DMS or SK-I inhalation resulted in a decrease in S1P amounts in BAL fluid to basal levels, accompanied by decreased eosinophil infiltration and peroxidase activity. The extent of inhibition caused by DMS inhalation was higher than that caused by SK-I. Like T helper 2 (Th2) cytokine release, OVA inhalation-induced increase in eotaxin expression was significantly suppressed by DMS pretreatment both at protein level in BAL fluid and at mRNA level in lung homogenates. Moreover, bronchial hyperresponsiveness to inhaled methacholine and goblet cell hyperplasia were improved by SPHK inhibitors. These data suggest that the inhibition of SPHK affected acute eosinophilic inflammation induced in antigen-challenged mouse model and that targeting SPHK may provide a novel therapeutic tool to treat bronchial asthma.

Adenoviral transfer of rho family proteins to lung cancer cells ameliorates cell proliferation and motility and increases apoptotic change.

Lung cancer is still a very severe disease which has a low survival rate due to local invasion and metastasis potentials in spite of many clinical challenges using anti-cancer drugs. Rho family small GTPases play pivotal roles in cell invasion and metastasis during carcinogenesis. In this study, we explored the inhibitory effect of adenoviral vector encoding dominant negative mutants of Rac, RhoA, and ROCK in human non-small cell lung carcinoma cell lines (A549 and SQ5) and mouse carcinoma cell line (Lewis lung carcinoma, LLC). These cells showed high expression of Rac, Rho, and ROCK, whereas only faint bands were detected in normal human lung epithelial cells, BET-1A. The efficiency of adenoviral vector transfer was stronger in A549 and SQ5 cells than LLC cells. Dominant negative forms of RhoA (Rho-DN) and Rac (Rac-DN) decreased cell proliferation in WST-8 assay and increased the number of apoptotic cells in both A549 and SQ5 cells by Hoechst 33258 and TUNEL staining. On the other hand, DN form of ROCK (ROCK-DN) did not show any apparent changes compared with the other proteins. Transwell chamber analysis showed that migration/invasion activity was significantly suppressed by gene transfection both in A549 and SQ5 cells and that ROCK-DN gene transfer required a higher multiplicity of infection to show effects similar to Rho and Rac. Although the effect of gene therapy is cell-dependent, these data suggest that adenoviral gene transfer with Rho family small GTPases is one good approach to lung cancer therapy.