Continuous positive airway pressure versus high-flow nasal cannula oxygen therapy for acute hypoxemic respiratory failure: A randomized controlled trial.

BACKGROUND AND OBJECTIVE: The relative effectiveness of initial non-invasive respiratory strategies for acute respiratory failure using continuous positive airway pressure (CPAP) or high-flow nasal cannula (HFNC) is unclear. METHODS: We conducted a multicenter, open-label, parallel-group randomized controlled trial to compare the efficacy of CPAP and HFNC on reducing the risk of meeting the prespecified criteria for intubation and improving clinical outcomes of acute hypoxemic respiratory failure. The primary endpoint was the time taken to meet the prespecified criteria for intubation within 28 days. RESULTS: Eighty-five patients were randomly assigned to the CPAP or HFNC group. Eleven (28.9%) in the CPAP group and twenty (42.6%) in the HFNC group met the criteria for intubation within 28 days. Compared with HFNC, CPAP reduced the risk of meeting the intubation criteria (hazard ratio [HR], 0.327; 95% CI, 0.148-0.724; p = 0.006). There were no significant between-group differences in the intubation rates, in-hospital and 28-day mortality rates, ventilator-free days, duration of the need for respiratory support, or duration of hospitalization for respiratory illness. Pulmonary oxygenation was significantly better in the CPAP group, with significantly lower pH and higher partial pressure of carbon dioxide, but there were no differences in the respiratory rate between groups. CPAP and HFNC were associated with few possibly causal adverse events. CONCLUSION: CPAP is more effective than HFNC at reducing the risk of meeting the intubation criteria in patients with acute hypoxemic respiratory failure.

Nationwide survey of refractory asthma with bronchiectasis by inflammatory subtypes.

RATIONALE: Bronchiectasis and bronchiolitis are differential diagnoses of asthma; moreover, they are factors associated with worse asthma control. OBJECTIVE: We determined clinical courses of bronchiectasis/bronchiolitis-complicated asthma by inflammatory subtypes as well as factors affecting them. METHODS: We conducted a survey of refractory asthma with non-cystic fibrosis bronchiectasis/bronchiolitis in Japan. Cases were classified into three groups, based on the latest fractional exhaled NO (FeNO) level (32 ppb for the threshold) and blood eosinophil counts (320/µL for the threshold): high (type 2-high) or low (type 2-low) FeNO and eosinophil and high FeNO or eosinophil (type 2-intermediate). Clinical courses in groups and factors affecting them were analysed. RESULTS: In total, 216 cases from 81 facilities were reported, and 142 were stratified: 34, 40 and 68 into the type 2-high, -intermediate and -low groups, respectively. The frequency of bronchopneumonia and exacerbations requiring antibiotics and gram-negative bacteria detection rates were highest in the type 2-low group. Eighty-seven cases had paired latest and oldest available data of FeNO and eosinophil counts; they were analysed for inflammatory transition patterns. Among former type 2-high and -intermediate groups, 32% had recently transitioned to the -low group, to which relatively low FeNO in the past and oral corticosteroid use contributed. Lastly, in cases treated with moderate to high doses of inhaled corticosteroids, the frequencies of exacerbations requiring antibiotics were found to be higher in cases with more severe airway lesions and lower FeNO. CONCLUSIONS: Bronchiectasis/bronchiolitis-complicated refractory asthma is heterogeneous. In patients with sputum symptoms and low FeNO, airway colonisation of pathogenic bacteria and infectious episodes are common; thus, corticosteroids should be carefully used.

Hochuekkito Combined with Pulmonary Rehabilitation in Apathetic Patients with Chronic Obstructive Pulmonary Disease: A Randomized Controlled Pilot Trial.

The main treatment goals for chronic obstructive pulmonary disease (COPD) are the reduction of its symptoms and future risks. The addition of the traditional herbal medicine Hochuekkito (TJ-41) treatment to pulmonary rehabilitation (PR) has been reported to improve dyspnea and health-related quality of life (HRQOL) in patients with COPD. However, the reason for this improvement is not sufficiently understood. The purpose of the present study was to investigate whether the addition of TJ-41 treatment to PR improves symptoms of apathy, dyspnea, and HRQOL and increases physical activity among apathetic patients with COPD. Apathetic patients with COPD were randomly assigned to receive low-intensity exercise with (TJ-41 group) or without (control group) TJ-41 treatment for 12 weeks. A total of 29.9% of COPD patients had apathetic symptoms without severe depression. After the 12-week treatment, Apathy Scale, Patient Health Questionnaire-9, visual analog scale for dyspnea, and COPD assessment test energy scores decreased significantly in the TJ-41 group (p < 0.05), but not in the control group. Additionally, the total number of steps taken was significantly higher in the TJ-41 group than in the control group. TJ-41 combined with PR may benefit apathetic patients with COPD with respect to apathy, dyspnea, HRQOL, and physical activity, but larger randomized placebo-controlled trials are required to validate the findings because of the small sample size and lack of placebo controls in this study.

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).

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).

[THE MINIMUM NUMBER OF SPUTUM SMEAR SAMPLES NEEDED FOR THE DIAGNOSIS OF TUBERCULOSIS].

[Objective] To determine whether three sputum examinations with fluorescent staining are necessary to diag- nose tuberculosis (TB) in our hospital. [Patients] From April 2005 to December 2012, 379 TB patients were admitted and received anti-TB therapy in our hospital. [Methods] A retrospective study was conducted to assess the positivity rates of sputum smears based on three exami- nations. The positivity rate of first sputum smear and the cumulative smear-positive rates in the second and third were determined. Then, we also determined difference of positivity rates in sputum properties, sampling procedures and cavity formation. [Results] Of the 379 patients who met the screening criteria, 300 tested positive based on the first sputum smear (79.2%). The positivity rate of the first sputum smears was higher in the purulent sputum group than in the mucous sputum group (91.2% vs. 72.3%). Cavity formation, and sputum extraction procedures were not related to the positivity rate of the first sputum smears. In the mucous sputum group, the cumulative smear-positive rate in the second test significantly rose, but did not rise in the third test. [Conclusions] Three sputum smear examinations were necessary in patients who submitted mucous sputum samples. It is important to get purulent sputum.

[AN OUTBREAK OF PULMONARY TUBERCULOSIS DUE TO DEFINITE EXOGENOUS REINFECTION AMONG ELDERLY INDIVIDUALS IN WELFARE FACILITIES].

PURPOSE: We report an outbreak of 64 cases of tuberculosis (TB) that spread in a welfare facility for elderly individuals. OBJECTIVE AND METHODS: First, 64 TB patients who had contact with the source patient were screened at our hospital. We examined the time course up to the discovery of symptoms and analyzed the results for variable numbers of tandem repeats (VNTR) and the drug susceptibility tests. Second, we performed chest computed tomography to examine lesions due to a previous TB infection. RESULT: The source patient had recurrent aspiration pneumonia. The delay in doctor consultation was considered day 0, and the delay of diagnosis was 267 days. On examining the contacts, we found that 29 patients had TB while 35 had a latent TB infection. Results of the VNTR and the drug susceptibility tests showed that all the patients who developed TB had the same pattern as that of the source patient. Chest computed tomography showed lesions due to a previous TB infection in 8 patients. CONCLUSION: Based on the results of the VNTR and drug susceptibility tests, we concluded that the outbreak was due to an exogenous infection from the same source. All 8 patients who showed lesions due to a previous TB infection were aged > 81 years, and TB in these patients was found to be due to exogenous re-infection.

Low-intensity noninvasive ventilation: Lower pressure, more exacerbations of chronic respiratory failure.

BACKGROUND: For patients with chronic respiratory failure (CRF) who are treated with noninvasive positive pressure ventilation (NPPV), a little is known regarding the effects of low-intensity NPPV (LI-NPPV) on the clinical course of CRF and the frequency of adjustments in these patients. OBJECTIVES: This study investigated the effects of LI-NPPV on the clinical course of patients with CRF as compared with patients who were treated with conventional NPPV (C-NPPV) and determined how frequently NPPV was adjusted during therapy. METHODS: Clinical data from 21 patients who received long-term NPPV were retrospectively analyzed. Patients were categorized into two groups based on the level of initial pressure support (PS): C-NPPV group (PS ≥ 10 cm H2O) and LI-NPPV group (PS < 10 cm H2O). RESULTS: Patients in the LI-NPPV group had significantly more exacerbations of CRF (P < 0.05). There was no significant difference in the number of patients who required adjustments of NPPV settings between the two groups. There was no significant difference in PaCO2 levels 1 month after the start of NPPV between the two groups; however, PaCO2 levels were significantly lower after 1 year in the C-group (P < 0.001). Seventy-one percent of LI-NPPV patients and 43% of C-NPPV patients needed NPPV adjustments. CONCLUSIONS: Attention should be paid to CRF patients who are initially administered LI-NPPV; they should be carefully observed because they can develop more exacerbations of CRF than patients undergoing C-NPPV. If possible, higher initial PS should be administered to prevent CRF exacerbations.

[[CASE OF TUBERCULOSIS COMPLICATIONS DURING PREGNANCY LEADING TO AN INFECTION OUTBREAK].]

A 31-year-old woman developed a constant cough during the 8th week of pregnancy and was diagnosed with bronchial asthma. She was prescribed prednisolone and inhaled corticosteroids. At 28 weeks of pregnancy, she showed worsening weight loss, fever, night sweats, hoarseness, and coughs. At 31 weeks of pregnancy, a scatter shadow and cavitary lesions were detected on the chest radiograph. Acid- fast bacilli smear test and tuberculosis (TB) polymerase chain reaction tests yielded positive results (G-8), and she was diagnosed with TB. Contact tracing and screening indicated 3 patients with TB onset and 18 patients with latent TB infec- tion attributed to the initial patient, who infected a total of 36 people. In the present case, physicians were reluctant to order a chest radiograph for fear of harming the fetus and did not order sputum or interferon gamma release (IGRA) assay tests either. The diagnosis was delayed by 152 days, which was considered as a factor that caused the outbreak. The diag- nosis of TB in a pregnant patient may be very challenging because symptoms may initially be ascribed to the pregnan- cy, and delayed diagnosis and treatment of military TB can lead to the death of the mother and fetus. Consequently, to ensure early diagnosis and treatment, chest radiography and sputum and IGRA tests are recommended for pregnant women who have TB symptoms or are at high risk for TB.

An analysis of etiology, causal pathogens, imaging patterns, and treatment of Japanese patients with bronchiectasis.

BACKGROUND: Bronchiectasis (BE), a syndrome that presents with persistent or recurrent bronchial sepsis related to irreversibly damaged and dilated bronchi, has not been well-characterized in Asians. This study aims to review the etiology, causal pathogens, imaging patterns, and treatment of BE and to define the prognostic factors for acute exacerbation in a Japanese population. METHODS: We performed a retrospective cohort study of 147 patients (104 women; median age, 73 years; range, 30-95 years) with BE at our institution using high-resolution computed tomography to identify imaging patterns and the area of pulmonary involvement. RESULTS: Common BE etiologies were idiopathic (N=50 [34%]), sinobronchial syndrome (N=37 [25%]), non-tuberculous mycobacteriosis (NTM; N=26 [18%]), and previous respiratory infection (N=21[14%]). Pseudomonas aeruginosa was the most common causal pathogen (24%). Common imaging patterns were cylindrical (66%) and mixed including cylindrical pattern (47%). The median number of involved lobes was 2; 49% of the patients had ≥ 3 involved lobes, and 49% had middle lobe and left lingula dominant BE. Patients with predominantly lower lobe BE comprised 4% of the NTM group and 48% of the non-NTM group (P<0.001). In multivariate analysis, cystic BE was a predictor for frequent exacerbations in non-NTM patients (OR=7.947; P=0.004) which led to increased hospital admissions (OR=4.691; P=0.004). CONCLUSIONS: Idiopathic and sinobronchial syndrome were common causes of BE. Etiology did not contribute to imaging pattern or predictors of exacerbations. Cystic BE was a predictor for frequent exacerbations in the non-NTM BE patients.

Phase II trial of S-1 as third-line or further chemotherapy in patients with advanced non-small-cell lung cancer.

OBJECTIVES: This study was conducted to evaluate the efficacy and safety of S-1 in patients with advanced non-small-cell lung cancer (NSCLC), receiving two or more prior chemotherapy regimens. METHODS: S-1 was administered orally for 14 consecutive days, followed by a 7-day rest period. This treatment course was repeated until disease progression or intolerable toxicity occurred. RESULTS: From 2010 to 2012, 45 patients were enrolled in this study. Of the 45 patients, 4 patients [8.9 %, 95 % confidence interval (CI) 0.6-17.2 %] exhibited a partial response and 24 patients (53.3 %) exhibited stable disease. The disease control rate was 62.2 % (95 % CI 48.1-76.4 %). Median progression-free survival was 71 days, and median survival time was 205 days. Four patients had grade 3 hematological toxicities, but toxicities of grade 4 were not observed in this study. CONCLUSION: Although S-1 monotherapy as third-line treatment or beyond was well tolerated, the response rate for this regimen did not demonstrate sufficient activity for patients with advanced NSCLC.

Pulmonary actinomycosis caused by Actinomyces cardiffensis.

We herein present the first case of pulmonary actinomycosis caused by Actinomyces cardiffensis (A. cardiffensis). A computed tomography (CT) examination revealed a nodule with cavitation in the left upper lobe of the lung. One month later, the lesion had almost disappeared, but a new nodule with peripheral consolidation had appeared in the right middle lobe. Because organizing pneumonia was suspected, prednisolone was begun and improvement was seen. However, two months after the initiation of corticosteroid administration, a chest CT scan showed a lung abscess. The patient underwent surgical resection of the abscess. A. cardiffensis was identified by an amplified 16S ribosomal DNA restriction analysis of a pus sample.

Sarcoid-like reaction in Cryptococcus neoformans infection.

We report a patient with Cryptococcus (C.) neoformans infection, who developed a case of sarcoid-like reaction (SLR). There have been reports of SLRs associated with malignancies. Although differentiating sarcoidosis from SLR is difficult, the patient was diagnosed as SLR because propionibacterium acnes bacterial (PAB) antibody staining of biopsy specimens was negative and the chest radiological findings improved after antifungal treatment. To our knowledge, this is the first report of SLR occurring during cryptococcal infection, and we believe that cryptococcal infection should be considered as a potential cause of SLR.

A case of sinobronchial syndrome complicated with myeloperoxidase antineutrophil cytoplasmic antibody associated vasculitis: review of the literature.

We report a case of long-standing sinobronchial syndrome complicated by microscopic polyangiitis (MPA) during the clinical course. The patient showed a mild elevation of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) 17 months prior to the diagnosis of MPA. Subsequently, her MPO-ANCA level gradually became more elevated, and finally her MPO-ANCA level peaked when purpura appeared. Histologic examination of the skin biopsy was consistent with leukocytoclastic vasculitis. Based on the pathological and clinical findings, a diagnosis of MPA was made. Corticosteroid therapy finally led to a remission of MPA with normalized MPO-ANCA titers.

[A case of alveolar hemorrhage 35 years after propylthiouracil treatment].

A 69-year-old woman had received oral treatment of propylthiouracil (PTU) under a diagnosis of hyperthyroidism for 35 years. In the first 10 days of January 2009, she noticed the development of a cough. In February of the same year, she consulted a clinic with bloody sputum. Chest X-ray films revealed diffuse infiltration in both lungs, and she came to our hospital for further examination. An alveolar hemorrhage was identified by bronchial alveolar lavage testing. Because the cough was relieved by stopping PTU administration and there has been no relapse during 2-year follow-up, this case was diagnosed as PTU-induced diffuse alveolar hemorrhage. Her myeloperoxidase (MPO) -anti-neutrophil cytoplasmic antibody (ANCA) level was 55 EU, suggesting ANCA-associated angitis. However, as a drug lymphocyte stimulation test to PTU was also positive and her MPO-ANCA level was not elevated, the onset mechanism of this case was unclear.