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.

[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.

Usefulness of the simultaneous determination of serum levels of theophylline and its metabolites in patients medicated with theophylline preparation.

OBJECTIVE: Measurement of the serum level of theophylline is essential for its proper use; however, it is difficult to infer the metabolic ability of individual patients by only the serum theophylline level and to decide the appropriate medication. In this study, we simultaneously measured serum theophylline and metabolite levels in patients treated with theophylline, and investigated their usefulness. EXPERIMENTAL: The subjects were asthma patients who visited the outpatient clinic of Respiratory Medicine, St Luke's International Hospital, between April and October 2003, and were medicated with sustained-release theophylline tablets (Theodur®). The serum level of theophylline and its metabolites was measured by HPLC in patients who gave written consent. RESULTS: A strong correlation was noted between the serum theophylline (TP) and 1,3-dimethyluric acid (DMU) levels of 52 patients (r = 0.670), and DMU/TP was about 0.04. In a patient whose the DMU/TP was 0.216, it was recognized that metabolic ability was promoted due to a history of smoking. DISCUSSION: In this study, it was shown that simultaneous measurement by HPLC of the serum level of theophylline and its metabolites and DMU/TP was useful to assess the metabolic ability of individual patients.

[Coinfection with Pneumocystis jirovecii and Mycobacterium tuberculosis in a patient with AIDS: a first report in Japan].

A 24-year-old man was admitted with a 7-month history of non-productive cough, and recent onset of fever and progressive dyspnea. A chest X-ray film and computed tomography (CT) scan showed bilateral infiltrates that indicated pneumocystis pneumonia (PCP). A transbronchial lung biopsy specimen demonstrated Pneumocystis jirovecii infection on Grocott staining, and was positive for acid-fast bacilli without necrotizing granuloma, which indicated coinfection with both Pneumocystis jirovecii and Mycobacterium tuberculosis. A test for human immunodeficiency virus (HIV) infection was positive, and his CD4 + T-lymphocyte count was 92 cells per cubic millimeter. Chest CT findings and pathological findings.were atypical for active tuberculosis (TB). It is important that clinicians should be aware that HIV-infected patients may have concurrent pulmonary TB and PCP, because the diagnosis is difficult.

[Impact of inhaled corticosteroid prescription at discharge from the emergency room on exacerbations of asthma in Japanese hospital].

BACKGROUND: Inhaled corticosteroid (ICS) therapy has been reported to improve relapses of asthma following emergency room (ER) discharge, but the benefits of ICS prescription at discharge from the ER are unclear. OBJECTIVE: To assess background of the patients who visit ER, and determine whether the prescription of ICS at ER reduces relapses in the patients with asthma. METHODS: A prospective multi-center cohort study was conducted at 32 Japanese ERs. Patients aged two to 82 years who visited ER with moderate to severe exacerbation of asthma underwent questionnaire and follow-up three and six months later. The primary observations were of the asthma-related hospitalizations, ER visits, and unscheduled visits. RESULTS: Among 343 asthma patients (Children: 120, Adults: 223), 33% of children and 12% of adult patients were classified as intermittent asthma, retrospectively. The patients with intermittent had the same rates of hospitalization (29.6%) and ER visits (46.2%) as those with persistent (hospitalization rate: 24.7%, ER visits: 53.1%, ns) before enrolled. The odds ratio for hospitalization in the patients received ICS at the discharge from the ER, compared with the patients who did not received ICS, yielded 0.256 (95% confidence interval, 0.069 to 0.942; p=0.040) by multinomial logistic regression model. CONCLUSION: Prescribing ICS at discharge from the ER to asthma patients is associated with the reduction of risk for asthma-related hospitalization. For patients discharged from the ER, including mild intermittent asthma, ICS might be prescribed.

[Two cases of invasive pulmonary aspergillosis mimicking pneumonia in lung cancer patients].

BACKGROUND: Invasive pulmonary aspergillosis (IPA) occurs predominantly in immunocompromised hosts, however increasing numbers of cases of IPA have been reported among basically immunocompetent patients who have some pulmonary abnormalities such as lung cancer and chronic obstructive pulmonary disease (COPD). CASE: Case 1. A 67-year-old man was admitted because of hemoptysis and purpura. He had COPD and small cell lung cancer and had finished chemotherapy 5 years previously. Chest X-ray showed pneumonia-like infiltration in his right lower lung field, and marked thrombocytopenia was pointed out. We started antibiotics and corticosteroids for community-acquired pneumonia (CAP) and idiopathic thrombocytopenic purpura. During treatment, we found Aspergillus fumigatus in his sputum culture and therefore added antifungal agents to his treatment. Despite intensive care, he died due to multi-organ dysfunction. Case 2. An 80-year-old man was admitted with fever and productive cough. He had COPD and non-small cell lung cancer and finished chemotherapy 2 months previously. Chest X-ray showed pneumonia-like infiltration in his right upper lung field. We started antibiotics and corticosteroids for acute exacerbation of COPD because of CAP. Several weeks later, after we observed initial improvement of his condition, pneumonia-like infiltration re-developed and Aspergillus fumigatus was detected in his sputum. We started antifungal agents and the treatment of IPA was successful, but he died because of idiopathic perforation of the sigmoid colon. CONCLUSION: In patients without myelosuppression, IPA could develop pneumonia-like pulmonary infiltrations.

[Physical therapy].

Recently, pulmonary rehabilitation program is widely considered one of the most effective and evidence-based treatment for not only chronic obstructive pulmonary disease (COPD) but many clinical situations including neuro-muscular disease, post-operative status and weaning period from the ventilator, etc. The essential components of a pulmonary rehabilitation program are team assessment, patient training, psycho-social intervention, exercise, and follow-up. In 2003, Japanese medical societies (J. Thoracic Society, J. Pul. Rehabilitation Society and J. Physiotherapist Society) made a new guideline for pulmonary rehabilitation, especially how to aproach the execise training. As for the duration after surgical operation, airway cleaning is the important technique to prevent post-operative complications including pneumonia. Postural dranage technique is well known for such condition, at the same time, several instruments (flutter vulve, positive expiratory mask, high frequecy oscillation, etc) were also used for the patient to expectrate airway mucus easier. Lung transplantation is a new method of treatment for the critically-ill patients with chronic respiratoy failure. Several techniques of physical therapy are must be needed before and after lung transplantation to prevent both pulmonary infection and osteoporosis.

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).

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.

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.

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.

[Advanced non-small cell lung cancer responded to both vinorelbine and carboplatin over long-term outpatient treatment].

We treated a patient with lung adenocarcinoma who responded to chemotherapy with vinorelbine (VNR) plus carboplatin (CBDCA) on an outpatient basis. The patient was a 68-year-old man. He visited a local physician complaining of wet coughing, headache and general fatigne. The symptoms remained unchanged and the patient was admitted to our department for treatment in June 2000. A massive shadow in the right upper lobe and multiple cerebral metastases were found. Based on this, the diagnosis was lung adenocarcinoma (T3N2M1, clinical stage IV). Whole-brain irradiation and systemic chemotherapy were initiated from July 2000. The patient received 1 course of systemic chemotherapy with vindesine (VDS) plus cisplatin (CDDP) on an inpatient basis. This regimen was replaced with combination therapy of paclitaxel (TXL) plus CBDCA in the outpatient setting, along with VNR plus CBDCA due to side effects caused by TXL. The cerebral metastases almost disappeared due to whole-brain irradiation. Chest CT after 3 courses revealed a reduction in primary tumor size. The VNR plus CBDCA combination therapy was continued for a further 6 courses. As the result, neither the primary tumor nor the cerebral metastases enlarged. The combination therapy with VNR plus CBDCA seems to be a useful regimen that can maintain high QOL and be conducted for a long term on an outpatient basis.

[Usefulness of sputum Gram staining in community-acquired pneumonia].

To evaluate the usefulness of sputum gram staining in community-acquired pneumonia (CAP), we reviewed 144 cases requiring hospitalization in the last 4 years. The sensitivity was 75.5%, specificity 68.2%, positive predictive value 74.1%, negative predictive value 69.8%, positive likelihood ratio 2.37, negative likelihood ratio 0.36 and accuracy 72.2% in 97 cases. Both sputum gram staining and culture were performed. Concerning bacterial pneumonia (65 cases), we compared the Gram staining group (n = 33), which received initial antibiotic treatment, based on sputum gram staining with the Empiric group (n = 32) that received antibiotics empirically. The success rates of the initial antibiotic treatment were 87.9% vs. 78.1% (P = 0.473); mean hospitalization periods were 9.67 vs. 11.75 days (P = 0.053); and periods of intravenous therapy were 6.73 vs. 7.91 days (P = 0.044), respectively. As for initial treatment, penicillins were used in the Gram staining group more frequently (P < 0.01). We conclude that sputum gram staining is useful for the shortening of the treatment period and the appropriate selection of initial antibiotics in bacterial pneumonia. We believe, therefore, that sputum gram staining is indispensable as a diagnostic tool CAP.

[Bronchiolitis obliterans organizing pneumonia after irradiation therapy for breast cancer].

We report three cases of bronchiolitis obliterans organizing pneumonia (BOOP) that developed after irradiation therapy following breast cancer. All patients presented with cough and fever for 3 to 10 months after the completion of irradiation. Chest radiographs and computed tomography (CT) in all three patients demonstrated a consolidation outside the irradiated fields. Their laboratory data revealed increased C-reactive protein and increased erythrocyte sedimentation rates. Transbronchial lung biopsy was performed in all patients, and plugs of granulation tissue in the bronchioles and interstitial infiltration by mononuclear cells were found. Corticosteroid treatment resulted in rapid clinical improvement. BOOP was diagnosed from the histological and clinical findings. Although the etiology of BOOP still remains unknown, there may be a subgroup of such patients in whom the BOOP is induced by irradiation for breast cancer. These cases were assumed to be in a series of reported cases of BOOP primed by radiotherapy.

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.