Home High-Flow Nasal Cannula Oxygen Therapy for Stable Hypercapnic COPD: A Randomized Clinical Trial.

Rationale: The long-term effects of using a high-flow nasal cannula for chronic hypercapnic respiratory failure caused by chronic obstructive pulmonary disease remain unclear. Objectives: To assess whether long-term high-flow nasal cannula use reduces the number of exacerbations and improves other physiological parameters in patients with chronic hypercapnic respiratory failure caused by chronic obstructive pulmonary disease. Methods: We enrolled 104 participants (aged ⩾40 yr) with daytime hypercapnia (Global Initiative for Chronic Obstructive Lung Disease stages 2-4) receiving long-term oxygen therapy (⩾16 h/d for ⩾1 mo) and randomly assigned them to high-flow nasal cannula/long-term oxygen therapy and long-term oxygen therapy groups. The primary endpoint was the moderate or severe exacerbation rate. We compared changes from baseline in arterial blood gas values, peripheral oxygen saturation, pulmonary function, health-related quality-of-life scores, and the 6-minute-walk test. Measurements and Main Results: High-flow nasal cannula use significantly reduced the rate of moderate/severe exacerbations (unadjusted mean count 1.0 vs. 2.5, a ratio of the adjusted mean count between groups [95% confidence interval] of 2.85 [1.48-5.47]) and prolonged the duration without moderate or severe exacerbations. The median time to first moderate or severe exacerbation in the long-term oxygen therapy group was 25 (14.1-47.4) weeks; this was not reached in the high-flow nasal cannula/long-term oxygen therapy group. High-flow nasal cannula use significantly improved health-related quality of life scores, peripheral oxygen saturation, and specific pulmonary function parameters. No safety concerns were identified. Conclusions: A high-flow nasal cannula is a reasonable therapeutic option for patients with stable hypercapnic chronic obstructive pulmonary disease and a history of exacerbations. Clinical trial registered with www.umin/ac.jp (UMIN000028581) and www.clinicaltrials.gov (NCT03282019).

Disseminated nocardiosis due to Nocardia terpenica.

We report the first case of disseminated nocardiosis due to trimethoprim/sulfamethoxazole-resistant Nocardia terpenica successfully treated with meropenem and clarithromycin. The patient travelled to Japan from Australia via Southeast Asia, which led to differential diagnoses of multiple lung nodules including miliary tuberculosis and melioidosis as well as nocardiosis. Because of variety of susceptibility depending on the Nocardia species, clinicians need to confirm the species and investigate its susceptibility.

Domiciliary High-Flow Nasal Cannula Oxygen Therapy for Patients with Stable Hypercapnic Chronic Obstructive Pulmonary Disease. A Multicenter Randomized Crossover Trial.

RATIONALE: A growing evidence base suggests a benefit of using high-flow nasal cannula oxygen therapy in the acute setting. However, the clinical benefit of domiciliary use of high-flow nasal cannula oxygen therapy in patients with chronic hypercapnic respiratory failure due to chronic obstructive pulmonary disease remains unclear. OBJECTIVES: To evaluate the efficacy and safety of high-flow nasal cannula oxygen therapy use in patients with stable chronic obstructive pulmonary disease. METHODS: We conducted a multicenter, randomized crossover trial comparing high-flow nasal cannula oxygen therapy plus long-term oxygen therapy with long-term oxygen therapy only in 32 adults with stable hypercapnic chronic obstructive pulmonary disease. Participants were randomized to receive either 6 weeks of high-flow nasal cannula oxygen therapy/long-term oxygen therapy using the myAIRVO 2 device followed by another 6 weeks of long-term oxygen therapy only or long-term oxygen therapy only followed by high-flow nasal cannula oxygen therapy/long-term oxygen therapy. The primary outcome was the change in quality of life as assessed by St. George's Respiratory Questionnaire for chronic obstructive pulmonary disease. A linear mixed-effects model was used to account for treatment effect, time effect, allocation effect, and participant effect. RESULTS: Of 32 study participants, 29 completed the study. At the end of 12 weeks, high-flow nasal cannula oxygen therapy/long-term oxygen therapy treatment improved the mean total St. George's Respiratory Questionnaire for chronic obstructive pulmonary disease score compared with long-term oxygen therapy only (7.8 points; 95% confidence interval, 3.7 to 11.9; P < 0.01). Similarly, high-flow nasal cannula oxygen therapy/long-term oxygen therapy treatment improved the arterial partial pressure of carbon dioxide (adjusted treatment effect, -4.1 mm Hg; 95% confidence interval, -6.5 to -1.7 mm Hg), pH (adjusted treatment effect, +0.02; 95% confidence interval, 0.01 to 0.02), and median nocturnal transcutaneous carbon dioxide pressure (adjusted treatment effect, -5.1 mm Hg; 95% confidence interval, -8.4 to -1.8 mm Hg). High-flow nasal cannula oxygen therapy/long-term oxygen therapy treatment did not improve the arterial partial pressure of oxygen, dyspnea, spirometry, lung volume, 6-minute walk test, or physical activity. The most frequent high-flow nasal cannula oxygen therapy-related adverse event encountered was nocturnal sweating (n = 6 [20.7%]). Four severe adverse events occurred (two in each group) and were deemed unrelated to the intervention. CONCLUSIONS: Six weeks of treatment with high-flow nasal cannula oxygen therapy improved health-related quality of life and reduced hypercapnia in patients with stable hypercapnic chronic obstructive pulmonary disease. Clinical trial registered with www.clinicaltrials.gov (NCT02545855) and www.umin/ac.jp (UMIN000017639).

Evaluation of the rapid immunochromatographic ODK0501 assay for Streptococcus pneumoniae antigen detection with nasopharyngeal swabs: preliminary report.

BACKGROUND: Early identification and control of pathogenic bacteria are important in the treatment of pneumonia. Currently, two rapid antigen detection kits for pneumococcal pneumonia are available: one uses urine samples and the other, named RAPIRUN® S. pneumoniae, uses sputum samples. RAPIRUN® has shown high sensitivity with nasopharyngeal swab samples from pediatric patients. In this study, we investigated the performance of RAPIRUN® with nasopharyngeal swabs from adult patients. METHODS: All adult patients diagnosed with pneumonia from November 2011 to April 2012 in St. Luke's International hospital were included in this cross-sectional study. Single sputum, nasopharyngeal swab, and urine samples obtained from patients were investigated using a rapid antigen detection kit. Sputum and blood cultures were also evaluated. We compared the characteristics of pneumococcal pneumonia patients diagnosed using RAPIRUN with a nasopharyngeal swab to those patients diagnosed using other methods. Sensitivity and specificity were also calculated. RESULTS: Seventeen out of 60 patients with pneumonia were diagnosed with pneumococcal pneumonia. In 4 out  of the 17 cases, a positive test result was obtained using RAPIRUN with a nasopharyngeal swab. The sensitivity and specificity were 23.5 and 100 %, respectively. CONCLUSION: RAPIRUN performed with nasopharyngeal swabs from adult patients exhibited lower sensitivity for the diagnosis of pneumococcal pneumonia than the other compared methods. The causative pathogen of pneumonia should be identified using not only sputum cultures or rapid antigen detection kits but also clinical features or gram staining of sputum.

Impact of Symptom Clusters on Quality of Life Outcomes in Patients from Japan with Advanced Nonsmall Cell Lung Cancers.

OBJECTIVE: Identify symptom clusters based on symptoms experienced by patients with advanced nonsmall cell lung cancers (NSCLCs), and examine the relationship between the symptom clusters and impairment in everyday life and quality of life (QOL). METHODS: Using the M.D. Anderson Symptom Inventory, 9 symptom items and the QOL Questionnaire (QLQ-C-30) evaluation apparatus from the European Organization for Research and Treatment of Cancer, we evaluated symptom severity, interference in daily life, and QOL. Factor analysis and multiple regression analysis techniques were used. RESULTS: Sixty patients with advanced NSCLCs seen in pulmonary medicine departments were included in the study. The average age of patients was 64.33 (standard deviation = 11.40). Thirty-six were male and 24 were female. Three symptom clusters were identified as fatigue/anorexia cluster (dry mouth, altered the sense of taste, drowsiness, fatigue/tiredness, and lack of appetite), pain cluster (anxiety, sadness, and pain), numbness cluster (numbness, leg weakness, and distress). The pain cluster had the strongest influence (adjusted R2 = 0.355) on daily life (emotions) while the numbness cluster most strongly affected walking. The fatigue/anorexia cluster explained 22.7% of role function variance. This symptom clustering may be unique among patients with advanced NSCLCs. CONCLUSIONS: Each of these clusters affected QOL and everyday life with varying degrees of influence. In clinical screening assessments, focusing on symptom clusters could provide tailored management strategies for patients with advanced NSCLCs. These care strategies may improve outcomes specifically for advanced NSCLCs patients.

Analysis of the clinical backgrounds of patients who developed respiratory acidosis under high-flow oxygen therapy during emergency transport.

Aim: High-flow oxygen is often administered to patients during emergency transport and can sometimes cause respiratory acidosis with disturbed consciousness, thereby necessitating mechanical ventilation. Although oxygen titration in chronic obstructive pulmonary disease patients during emergency transport reduces mortality rates, the clinical risk factors for respiratory acidosis in emergency settings are not fully understood. Therefore, we analyzed the clinical backgrounds of patients who developed respiratory acidosis during pre-hospital transport. Methods: This was a retrospective study of patients who arrived at our hospital by emergency transport in 2010 who received high-flow oxygen while in transit. Respiratory acidosis was defined by the following arterial blood gas readings: pH, ≤7.35; PaCO 2, ≥45 mmHg; and HCO 3-, ≥24 mmol/L. The risk factors were identified using multivariable logistic regression analysis. Results: In 765 study patients, 66 patients showed respiratory acidosis. The following risk factors for respiratory acidosis were identified: age, ≥65 years (odds ratio [OR] 1.4; 95% confidence interval [CI], 0.7-2.8); transportation time, ≥10 min (OR 2.0; 95% CI, 1.1-3.7); three digits on the Japan Coma Scale (OR 3.1; 95% CI, 1.7-5.8); percutaneous oxygen saturation, ≤90% (OR 1.6; 95% CI, 0.8-3.0); tuberculosis (OR 4.5; 95% CI, 1.4-15.1); asthma (OR 1.8; 95% CI, 0.6-5.3); pneumonia (OR 1.5; 95% CI, 0.7-3.1); and lung cancer (OR 3.9; 95% CI, 1.5-10.1). These underlying diseases as risk factors included both comorbid diseases and past medical conditions. Conclusions: The factors identified may contribute to the development of respiratory acidosis. Further studies on preventing respiratory acidosis will improve the quality of emergency medical care.

Efficacy of early switch from intravenous to oral antimicrobials in patients with aspiration pneumonia: A prospective observational study.

BACKGROUND: Previous reports have documented the efficacy of an early switch from intravenous to oral antimicrobials in community-acquired pneumonia, but not aspiration pneumonia. Therefore, we assessed the feasibility and efficacy of these newly developed criteria for community-acquired pneumonia in patients with aspiration pneumonia. METHODS: This prospective observational study included consecutive patients admitted with aspiration pneumonia over a 10-month period at St. Luke's International Hospital; we excluded patients that required intensive care. The criteria for an early switch were stability of vital signs (temperature ≤ 38 °C; respiratory rate ≤ 24 breaths/min; pulse rate ≤ 100 beats/min for >24 h) and a successful swallow evaluation (repetitive saliva swallowing test score ≥ 2; modified water swallowing test score ≥ 4). Our primary endpoint was successful completion of antimicrobial treatment 30 days after the switch, without reversion to intravenous antimicrobials. Our anticipated success rate was set as 60-75%, based on a previous study. RESULTS: Of the 70 patients admitted with aspiration pneumonia, 32 (45.7%) were excluded, and 38 (54.3%) met the inclusion criteria. Of these 38 patients, 29 (76.3%) met the switch criteria. The median duration of hospital stay for the included patients was 16 (5-30) days and 30 (12-68) days, respectively (P=0.03). Among patients who met the switch criteria, 26 (89.7%) completed oral treatment successfully while 3 (10.3%) reverted to intravenous antimicrobials. CONCLUSIONS: Approximately 75% of patients met the switch criteria; of these, nearly 90% underwent safe conversion to oral therapy. These results demonstrate the efficacy and feasibility of our switch criteria.

[Safety of pemetrexed according to the duration of vitamin B12 and folic acid supplementation prior to the first dose of pemetrexed].

OBJECTIVE: Administration of vitamin B12 and folic acid for 7 days prior to the administration of the first dose of pemetrexed is recommended. However, vitamin supplementation rarely is initiated less than 7 days prior to the first dose of pemetrexed. Therefore, we analyzed the safety of pemetrexed with vitamin supplementation for less than 7 days prior to the first dose of pemetrexed. METHODS: Patients were classified into 2 groups according to the duration of vitamin supplementation prior to the first dose of pemetrexed: group A received vitamin supplementation for 7 days or more, and group B received vitamin supplementation for less than 7 days. We analyzed adverse effects, such as myelosuppression, rash, and diarrhea, after 1 cycle of pemetrexed therapy. RESULTS: A total of 70 patients were administered pemetrexed; 40 patients were men and 30 were women with a median age of 64.5 years(range, 43-86 years). A total of 57 patients were classified into group A and 13 into group B; 33 patients were administered pemetrexed as a first-line treatment. Neutropenia of Grade 3 or more was observed in 4/49(8.2%)patients in group A and 2/13(15.4%)patients in group B(p=0.60). There were no significant differences in the rates of occurrence of neutropenia, rash, and diarrhea. CONCLUSION: This retrospective study indicated that patients could be safely treated with pemetrexed if vitamin supplementation is initiated for less than 7 days prior to the first administration of pemetrexed. However, further studies are needed because of a lack of statistical power and adjustment for confounding factors.

A patient with lung squamous cell carcinoma presenting with severe cardiac dysfunction similar to dilated cardiomyopathy with left bundle branch block induced by myocardial metastasis.

A patient with severe cardiac dysfunction similar to dilated cardiomyopathy expired because of lung squamous cell carcinoma. He was admitted with respiratory failure and was diagnosed with congestive heart failure due to dilated cardiomyopathy based on the chest X-ray, electrocardiography, echocardiography, and coronary angiography. Chest computed tomography showed a mass shadow in the right lower lobe, and the patient was diagnosed with lung squamous cell carcinoma by bronchoscopy. The patient expired, and the autopsy revealed that a myocardial metastasis disrupted the cardiac-conduction system without dilated cardiomyopathy in myocytes. Left bundle branch block caused by myocardial metastasis presumably induced left cardiac dysfunction.

Bronchoscopic visualization of the alveoli.

We report a rare case in which we were able to visualize the lung alveoli through the bronchial wall by a bronchoscope in a patient with marked bronchiectasis and performed lung biopsy safely under direct vision. An 80-year-old woman presented with complaints of a severe persistent cough for the past 6 months. A chest computed tomography scan revealed diffuse interstitial pneumonia with marked bronchiectasis. Bronchoscopy also revealed marked bronchiectasis. After inserting the bronchoscope into the 10th-generation bronchus, we observed a honeycomb pattern through the bronchial wall, which represented the alveoli. We perforated the bronchial wall by using biopsy forceps and performed lung biopsy under direct vision. The pathologic diagnosis revealed interstitial pneumonia with epithelioid granuloma and cholesterin-like substance, which were indicative of hypersensitivity pneumonia. The routine performance of true "trans"-bronchial lung biopsy will be possible if a thin bronchoscope with high-quality imaging is developed in the future.

Long-term survival of a patient with extensive small cell carcinoma of unknown primary etiology complicated by nephrotic syndrome.

We experienced a case of nephrotic syndrome (membranous nephropathy) complicated by extensive small cell carcinoma of unknown primary etiology that was diagnosed based on the findings of bilateral cervical and mediastinal lymphadenopathy. A complete cancer response and proteinuria remission following radical chemoradiation therapy were documented. The status of a complete response and nephrosis remission persisted for more than three years. This is the first report to demonstrate the long-term survival of a patient with extensive small cell carcinoma of unknown primary etiology complicated by paraneoplastic nephrotic syndrome.

A case of pulmonary tumor thrombotic microangiopathy diagnosed by transbronchial lung biopsy and treated with chemotherapy and long-term oxygen and anticoagulation therapies.

A 41-year-old woman, who underwent breast resection for cancer of the right breast and adjuvant chemotherapy 2 years ago, was admitted to our hospital due to shortness of breath upon exertion. High-resolution computed tomography of the chest showed small nodular opacities in the peribronchiolar area in both lungs, as well as mediastinal and hilar lymphadenopathy. A transbronchial lung biopsy revealed breast cancer metastasis and pulmonary tumor thrombotic microangiopathy (PTTM). Treatment of PTTM is rarely reported due to the difficulty of antemortem diagnosis; however, the patient was effectively treated with chemotherapy and oxygen and anticoagulation therapies for 3 months.

Impact of blood cultures on the changes of treatment in hospitalized patients with community-acquired pneumonia.

BACKGROUND: Initial blood cultures (BCs) with severe community-acquired pneumonia (CAP) are warranted. However, other than severity, the specific contributing factors that affect the decision to change antimicrobial agents have not been evaluated previously. METHODS: Consecutive adults with CAP hospitalized between January 2008 and December 2010 were assessed retrospectively. We enrolled those who were over 18 years old with typical symptoms of pneumonia and with an infiltrate consistent with pneumonia, from which 2 sets of BCs were obtained. Those who had been immunocompromised, hospitalized, or prescribed antibiotics in the past 30 days were excluded. We retrospectively assessed the factors contributing to the change in antimicrobial agents as well as the frequency of these changes in the enrolled patients based on the initial BC results. RESULTS: In total, 793 patients with initial diagnosis of CAP were admitted; 399 met the inclusion criteria. Among them, 386 were made definitive diagnosis of CAP after admission (the remaining 13 were made alternative diagnosis [non-pneumonia illnesses]). BC results were positive in 17 (4.4%) out of 386 CAP patients, among whom antimicrobial therapy was changed based on the BC results in 8 (2.1%) (Pneumonia Severity Index [PSI] grade IV; 2, PSI grade V; 6). Alternative diagnosis after admission was contributing factors for changing antimicrobial agents based on the positive blood culture results. CONCLUSIONS: The use of BCs should be limited to patients with very severe cases. It would be helpful to find alternative diagnosis and modify treatment.

Effect of switching tiotropium HandiHaler® to Respimat® Soft Mist™ Inhaler in patients with COPD: the difference of adverse events and usability between inhaler devices.

BACKGROUND: Recently, tiotropium Respimat® Soft Mist™ Inhaler has been developed. Respimat is a multidose and propellant-free kit. The aerosol generated from Respimat improved lung drug deposition and required a lower dose of drug than HandiHaler®. The aim of this study is to assess the effect of switching from tiotropium HandiHaler to Respimat in patients with chronic obstructive pulmonary disease (COPD). METHODS: Thirty-four patients with COPD who received 18 µg of tiotropium delivered by the HandiHaler once daily were enrolled in this study between May and September 2010. Symptoms, adverse events, pulmonary functions, and usability of inhaler devices were assessed before and 12 weeks after switching from HandiHaler to 5 µg of tiotropium delivered by the Respimat. Symptoms and adverse events were also assessed 4 and 12 weeks after switching. Dyspnea was evaluated using the British Medical Research Council dyspnea scale. The usability of inhaler devices was scored using a 12-step checklist. RESULTS: Twenty-nine patients were followed until 12 weeks after switching. The median FEV1 (forced expiratory volume in 1 sec) values before and 12 weeks after switching to Respimat were 1.41 L and 1.60 L, respectively. Dry mouth appeared to improve after switching to Respimat. Cough just after inhalation was observed in seven patients until 4 weeks after switching. However, six patients overcame cough as they got used to Respimat. Regarding the handling of inhaler devices, patients were not good at breathing out before inhalation and holding their breath just after inhalation both with HandiHaler and with Respimat. However, in general, both inhalers were considered to be easy to use. Twenty-one patients replied that handling of Respimat was easier than that of HandiHaler. CONCLUSIONS: There was no major problem in switching from tiotropium HandiHaler to Respimat. Respimat and HandiHaler showed similar effects and usability. However, we should be aware of cough just after inhalation with Respimat.

Miliary brain metastases in 2 cases with advanced non-small cell lung cancer harboring EGFR mutation during gefitinib treatment.

Here we report 2 cases of non-small cell lung cancer (NSCLC) with sensitive epidermal growth factor receptor (EGFR) gene mutation that developed miliary brain metastases characterized by dementia and disorientation during gefitinib therapy. One patient's therapy was switched from gefitinib to chemotherapy followed by whole brain radiotherapy (WBRT), which resulted in disease progression with coma. Gefitinib reinitiation improved the patient's symptoms. The other patient continued gefitinib during WBRT and achieved complete remission of the miliary metastases and lived 18 months longer. These results suggest that gefitinib concomitant with WBRT is an optional strategy for the treatment of patients with EGFR-mutated NSCLC with miliary metastases to prevent disease flare.

Bronchiolitis obliterans organising pneumonia syndrome presenting with neutrophilia in bronchoalveolar lavage fluid after breast-conserving therapy.

A 61-year-old female presented with a dry cough and fever 4 months after tangential radiation therapy (RT) following conserving surgery for breast cancer. Chest radiography and CT demonstrated consolidation with air bronchogram outside the irradiated area. Neutrophil granulocytes were abundant in bronchoalveolar lavage fluid (BALF) (39.6% of total cells), and transbronchial lung biopsy revealed organising pneumonia (OP) histologically. Antibiotic therapy had no effect, but corticosteroid therapy brought about clinical improvement. Her condition was diagnosed as bronchiolitis obliterans OP (BOOP) syndrome. Lymphocytic BALF has been identified as a characteristic of BOOP syndrome induced after RT for breast cancer. The BALF in this case, however, was neutrophilic. In our analysis of differential cell counts in the BALF of 24 patients with BOOP syndrome, the BALF was neutrophilic (>5%) in 16 (76%) cases, and the neutrophilia was severe in some of those patients.