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.

Circulating Extracellular Vesicle Levels in Patients with Coronavirus Disease 2019 Coagulopathy: A Prospective Cohort Study.

Coronavirus disease 2019 (COVID-19) is associated with coagulopathy. However, the underlying mechanisms are not completely understood. We evaluated the association between COVID-19 coagulopathy and extracellular vesicle (EV) levels. We hypothesized that several EV levels would be higher in COVID-19 coagulopathy patients than in non-coagulopathy patients. This prospective observational study was conducted in four tertiary care faculties in Japan. We enrolled 99 COVID-19 patients (48 with coagulopathy and 51 without coagulopathy) aged ≥20 years who required hospitalization, and 10 healthy volunteers; we divided the patients into coagulopathy and non-coagulopathy groups according to the D-dimer levels (≥1 µg/mL and <1 µg/mL, respectively). We used flow cytometry to measure the tissue-factor-bearing, endothelium-derived, platelet-derived, monocyte-derived, and neutrophil-derived EV levels in platelet-free plasma. The EV levels were compared between the two COVID-19 groups as well as among the coagulopathy patients, non-coagulopathy patients, and healthy volunteers. No significant difference was found in EV levels between the two groups. Meanwhile, the cluster of differentiation (CD) 41 + EV levels were significantly higher in COVID-19 coagulopathy patients than in healthy volunteers (549.90 [255.05-984.65] vs. 184.3 [150.1-254.1] counts/µL, p = 0.011). Therefore, CD41+ EVs might play an essential role in COVID-19 coagulopathy development.

ARDS Clinical Practice Guideline 2021.

BACKGROUND: The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. METHODS: The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. RESULTS: Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4-8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D), we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D), we suggest against routinely implementing NO inhalation therapy (GRADE 2C), and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). CONCLUSIONS: This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jsicm.org/publication/guideline.html ). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

ARDS clinical practice guideline 2021.

BACKGROUND: The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. METHODS: The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. RESULTS: Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4-8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D); we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D); we suggest against routinely implementing NO inhalation therapy (GRADE 2C); and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). CONCLUSIONS: This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jrs.or.jp/publication/jrs_guidelines/). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

Optimal Upper Limits of Plateau Pressure for Patients With Acute Respiratory Distress Syndrome During the First Seven Days: A Meta-Regression Analysis.

BACKGROUND: The effects of plateau pressure during the initial days of mechanical ventilation on outcomes for patients with acute respiratory distress syndrome have not been fully examined. We conducted meta-regression analysis of plateau pressure during the first 7 days using randomized control trials to investigate the optimal upper limits of plateau pressure on different days of mechanical ventilation. METHODS: Randomized controlled trials comparing two mechanical ventilation strategies with lower and higher plateau pressures in patients with acute respiratory distress syndrome were included. Meta-regression analysis was performed to determine the association of plateau pressure with mortality on days 1, 3, and 7 of mechanical ventilation. RESULTS: After evaluation of 2,975 citations from a comprehensive search across electronic databases, 14 studies were included in the final qualitative analysis. A total of 4,984 patients were included in the quantitative analysis. As a result of the pairwise comparison, overall short-term mortality was significantly higher for patients with plateau pressures over 32 cm H2O during the first 3 days after intensive care unit (ICU) admission (day 1: relative risk (RR), 0.77; 95% confidence interval (CI), 0.66 - 0.89; I2 = 0%; day 3: RR, 0.76; 95% CI, 0.64 - 0.90; I2 = 0%), but not on day 7 (RR, 0.82; 95% CI, 0.65 - 1.04; I2 = 16%). Plateau pressures below 27 cm H2O and 30 cm H2O were not associated with an absolute risk reduction of short-term mortality. According to univariable meta-regression analysis, mortality was significantly associated with plateau pressure on day 1 (ß = 0.01 (95% CI, 0.002 - 0.024), P = 0.02). On days 3 and 7, however, no significant difference was detected. When the cutoffs were set at 27, 30 and 32 cm H2O on day 1, which showed a significant difference, plateau pressure tended to be associated with increased mortality at pressures above the cut-off values, and there were no significant differences at pressures below the cut-off values, regardless of the cutoff used. CONCLUSIONS: This study suggests that the optimal cut-off value for plateau pressure may be 27 cm H2O especially during the initial period of mechanical ventilation, although this association may not continue during the latter period of mechanical ventilation.

Occurrence and incidence rate of peripheral intravascular catheter-related phlebitis and complications in critically ill patients: a prospective cohort study (AMOR-VENUS study).

BACKGROUND: The lack of precise information on the epidemiology of peripheral intravascular catheter (PIVC)-related phlebitis and complications in critically ill patients results in the absence of appropriate preventive measures. Therefore, we aimed to describe the epidemiology of the use of PIVCs and the incidence/occurrence of phlebitis and complications in the intensive care unit (ICU). METHODS: This prospective multicenter cohort study was conducted in 23 ICUs in Japan. All consecutive patients aged ≥ 18 years admitted to the ICU were enrolled. PIVCs inserted prior to ICU admission and those newly inserted after ICU admission were included in the analysis. Characteristics of the ICU, patients, and PIVCs were recorded. The primary and secondary outcomes were the occurrence and incidence rate of PIVC-related phlebitis and complications (catheter-related blood stream infection [CRBSI] and catheter failure) during the ICU stay. RESULTS: We included 2741 patients and 7118 PIVCs, of which 48.2% were inserted in the ICU. PIVC-related phlebitis occurred in 7.5% (95% confidence interval [CI] 6.9-8.2%) of catheters (3.3 cases / 100 catheter-days) and 12.9% (95% CI 11.7-14.2%) of patients (6.3 cases / 100 catheter-days). Most PIVCs were removed immediately after diagnosis of phlebitis (71.9%). Grade 1 was the most common phlebitis (72.6%), while grade 4 was the least common (1.5%). The incidence rate of CRBSI was 0.8% (95% CI 0.4-1.2%). In cases of catheter failure, the proportion and incidence rate per 100 intravenous catheter-days of catheter failure were 21% (95% CI 20.0-21.9%) and 9.1 (95% CI 8.7-10.0), respectively. CONCLUSION: PIVC-related phlebitis and complications were common in critically ill patients. The results suggest the importance of preventing PIVC-related complications, even in critically ill patients. TRIAL REGISTRATION: UMIN-CTR, the Japanese clinical trial registry (registration number: UMIN000028019 , July 1, 2017).

Repetitive instructions at short intervals contribute to the improvement of inhalation technique.

BACKGROUND: Inhaled medicines are key drugs for the treatment of asthma or chronic obstructive pulmonary disease. However, the variety of inhaler devices and complicated inhalation procedures have created confusion among patients, affecting their correct understanding of inhalation. Recent studies reported that up to 80% of patients made technical errors in inhalation and emphasized the necessity for patient education. OBJECTIVE: We aimed to assess the importance of inhalation-related instructions and to find clinical factors associated with improvements in the inhalation technique. METHODS: We conducted a retrospective, single-center study at a regional core hospital in Japan. Physicians and community pharmacists constructed an interactive instruction system and shared a common inhalation procedure manual. Patients who received instructions for the inhalation technique at least 3 times were recruited. RESULTS: A total of 125 patients were analyzed in this study. The median age was 73 years (interquartile range, 67-80 years). At the second visit, 67 patients (53.6%) failed to correctly perform the technique despite being guided at the first visit. At the third visit, 48.8% of patients made some errors. After excluding 40 patients who were not subjected to analysis, the remaining 85 were divided into "improvement" and "no-improvement" groups. The total improvement rate was 57.6%. The median time interval between consecutive instructions in the "improvement" groups was 84 days, whereas that in the "no-improvement" group was 128 days (p < 0.05, U test). No significant difference in the age, sex, or primary disease was seen between these groups. CONCLUSION: Repetitive instructions at shorter intervals may be helpful for patients to develop and maintain an improved inhalation technique.

Prognostic values of the Berlin definition criteria, blood lactate level, and fibroproliferative changes on high-resolution computed tomography in ARDS patients.

BACKGROUND: In the Berlin definition, acute respiratory distress syndrome (ARDS) is stratified into three stages according to oxygenation severity at the onset. The relevance between ARDS severity and prognosis varies among published reports and has not been verified, especially in Asian patients. METHODS: In this study, we examined the associations between the Berlin definition criteria and prognosis and clinical parameters, including high-resolution computed tomography (HRCT) scores of fibroproliferative changes of the lungs. One hundred fifty-three patients (45 females; mean age, 67 y/o), who met the Berlin definition and received treatment in our intensive care unit between January 2012 and December 2015, were enrolled. RESULTS: The severity of ARDS was mild in 42 patients, moderate in 71, and severe in 40. The underlying diseases included pneumonia in 56 patients and aspiration in 43. Forty-two (27.5%) patients were deceased within 30 days, and the 30-day mortality was 10% in mild ARDS, 23% in moderate, and 55% in severe, which were significantly different (P <  0.05). In the non-survivors, APACHE II, SOFA, and SAPS II scores were higher than in the survivors (P <  0.001). Multivariate analyses revealed that elevated blood lactate level (≥ 2.0 mmol/L) and increased HRCT scores were significantly associated with weaning failure and 30-day mortality of the patients with ARDS. CONCLUSIONS: These results suggested that the severity criteria in the Berlin definition might be associated with the prognosis of the patients. Blood lactate levels and HRCT score might be predictive of the outcome of patients with ARDS.

Optimal duration of prone positioning in patients with acute respiratory distress syndrome: a protocol for a systematic review and meta-regression analysis.

INTRODUCTION: Several systematic reviews and meta-analyses have demonstrated that prolonged (≥16 hours) prone positioning can reduce the mortality associated with acute respiratory distress syndrome (ARDS). However, the effectiveness and optimal duration of prone positioning was not fully evaluated. To fill these gaps, we will first investigate the effectiveness of prone positioning compared with the conventional management of patients with ARDS, regarding outcomes using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Second, if statistical heterogeneity in effectiveness with regard to short-term mortality (intensive care unit death or ≤30-day mortality) is shown, we will conduct a meta-regression analysis to explore the association between duration and effectiveness, and determine the optimal duration of prone positioning. METHOD AND ANALYSIS: Relevant studies are collected using PubMed/MEDLINE, Embase, Cochrane Central Register of Controlled Trials and the WHO International Clinical Trials Platform Search Portal. Randomised controlled trials comparing prone and supine positioning in adults with ARDS will be included in the meta-analysis. Two independent investigators will screen trials obtained by search eligibility and extract data from selected studies to standardised data recording forms. For each selected trial, the risk of bias and quality of evidence will be evaluated using the GRADE system. Meta-regression analyses will be performed to identify the most important factors associated with short-term mortality, and subgroup analysis will be used to analyse the following: duration of mechanical ventilation in the prone position per day, patient severity, tidal volume and cause of ARDS. If heterogeneity or inconsistency among the studies is detected, subgroup analysis will be conducted on factors that may cause heterogeneity. ETHICS AND DISSEMINATION: This study requires no ethical approval. The results obtained from this systematic review and meta-analysis will be disseminated through international conference presentations and publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42017078340.

Anti-inflammatory roles of mesenchymal stromal cells during acute Streptococcus pneumoniae pulmonary infection in mice.

BACKGROUND: Pneumonia is the fourth leading cause of death worldwide, and Streptococcus pneumoniae is the most commonly associated pathogen. Increasing evidence suggests that mesenchymal stromal cells (MSCs) have anti-inflammatory roles during innate immune responses such as sepsis. However, little is known about the effect of MSCs on pneumococcal pneumonia. METHODS: Bone marrow-derived macrophages (BMDMs) were stimulated with various ligands in the presence or absence of MSC-conditioned medium. For in vivo studies, mice intranasally-inoculated with S. pneumoniae were intravenously treated with MSCs or vehicle, and various parameters were assessed. RESULTS: After stimulation with toll-like receptor (TLR) 2, TLR9 or TLR4 ligands, or live S. pneumoniae, TNF-α and interleukin (IL)-6 levels were significantly decreased, whereas IL-10 was significantly increased in BMDMs cultured in MSC-conditioned medium. In mice, MSC treatment decreased the number of neutrophils in bronchoalveolar lavage fluid (BALF) after pneumococcal infection, and this was associated with a decrease in myeloperoxidase activity in the lungs. Levels of proinflammatory cytokines, including TNF-α, IL-6, GM-CSF and IFN-γ, were significantly lower in MSC-treated mice, and the bacterial load in the lung after pneumococcal infection was significantly reduced. In addition, histopathologic analysis confirmed a decrease in the number of cells recruited to the lungs; however, lung edema, protein leakage into the BALF and levels of the antibacterial protein lipocalin 2 in the BALF were comparable between the groups. CONCLUSIONS: These results indicate that MSCs could represent a potential therapeutic application for the treatment of pneumonia caused by S. pneumoniae.

The efficacy, safety, and feasibility of inhaled amikacin for the treatment of difficult-to-treat non-tuberculous mycobacterial lung diseases.

BACKGROUND: In multidrug regimens, including an intravenous aminoglycoside (e.g. amikacin [AMK]) is recommended for difficult-to-treat non-tuberculous mycobacterial (NTM) lung diseases. We aimed to evaluate the efficacy, safety, and feasibility of inhaled AMK therapy in patients with difficult-to-treat NTM lung diseases in a retrospective chart review. METHODS: The study population consisted of patients with NTM lung diseases who received combination therapy, including inhaled AMK therapy, at Keio University Hospital (Tokyo, Japan), from January 2014 through May 2016. A total of 26 cases, consisting of 23 Mycobacterium avium complex (MAC) and three Mycobacterium abscessus complex (MABC) infections cases, were included in this study. The efficacy, safety, and feasibility of inhaled AMK therapy were retrospectively investigated. The Research Ethics Committee of Keio University Hospital approved this study, and informed consent was obtained from all patients. RESULTS: All 26 patients were culture-positive at enrolment. Twenty-three of the 26 patients (88.5%), including 21/23 MAC patients (91.3%) and 2/3 MABC patients (66.7%), were administered inhaled AMK therapy for >3 months. The proportion of patients who had clinical symptoms, including, cough and sputum, declined after inhalation AMK therapy. Ten of the 23 patients (43.5%) who received AMK inhalation, including 8/21 MAC (38.1%) and 2/2 MABC patients (100%), showed sputum conversion, defined as at least three consecutive negative sputum cultures. Seven of the 23 patients, including, 5/21 MAC and 2/2 MABC patients, showed improvements in high-resolution computed tomography imaging of the chest. In addition, the serum AMK trough levels before the second inhalation were <1.2 µg/mL in all 26 patients, with no occurrence of severe adverse events, such as renal toxicity. One patient (3.8%) experienced auditory toxicity, in the form of tinnitus. However, this symptom was reversible, after temporary interruption of AMK, the patient was able to safely resume the therapy. CONCLUSIONS: Inhaled AMK therapy is an effective and feasible therapy for difficult-to-treat NTM lung disease.

Optimal plateau pressure for patients with acute respiratory distress syndrome: a protocol for a systematic review and meta-analysis with meta-regression.

INTRODUCTION: Lower tidal volume ventilation in patients with acute respiratory distress syndrome (ARDS) is a strategy to reduce the plateau pressure and driving pressure to limit ventilator-induced lung injury (VILI). Several randomised controlled trials (RCTs) and meta-analyses showed that limiting both the plateau pressure and the tidal volume decreased mortality, but the optimal plateau pressure to demonstrate a benefit is uncertain. The aim of this systematic review is to investigate the optimal upper limit of plateau pressure in patients with ARDS to prevent VILI and improve clinical outcomes using meta-analysis with and without meta-regression. METHODS AND ANALYSIS: RCTs comparing two mechanical ventilation strategies will be included, with lower plateau pressure and with higher plateau pressure, among patients with ARDS and acute lung injury. Data sources include MEDLINE via the NCBI Entrez system, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and Ichushi, a database of papers in Japanese. Two of three physicians will independently screen trials obtained by search for eligibility, and extract data from included studies onto standardised data recording forms. For each included trial, the risk of bias and the quality of evidence will be evaluated using the Grading of Recommendation Assessment Development and Evaluation system. ETHICS AND DISSEMINATION: This study does not require ethical approval. The results of this systematic review and meta-analysis with and without meta-regression will be disseminated through conference presentation and publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: CRD42016041924.

Alectinib as a treatment option following recovery from crizotinib-induced interstitial lung disease in patients with anaplastic lymphoma kinase-positive advanced non-small-cell lung cancer.

Crizotinib is a tyrosine kinase inhibitor that displays antitumor activity against anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer. However, crizotinib-associated interstitial lung disease (ILD) has been reported as an infrequent, but potentially fatal complication. We herein describe the case of a 63-year-old male patient with ALK-rearranged advanced lung adenocarcinoma. Chest computed tomography (CT) revealed extensive bilateral ground-glass opacity and airspace consolidation with traction bronchiectasis on day 27 of crizotinib therapy. No signs of infection or left heart failure were identified and we considered the lesions to be consistent with crizotinib-induced ILD. Following corticosteroid treatment and discontinuation of crizotinib, CT revealed improvement of ILD, but also showed regrowth of the tumor. Alectinib, a novel alternative ALK inhibitor, was initiated, and has been successfully continued, with neither disease progression nor recurrence of ILD. The present case indicates that alectinib may be considered as an alternative agent in cases of crizotinib-induced ILD, irrespective of the pattern of ILD, i.e., a diffuse alveolar damage (DAD) or non-DAD pattern, with careful observation.

Histone Deacetylase Inhibition Protects Mice Against Lethal Postinfluenza Pneumococcal Infection.

OBJECTIVES: Secondary bacterial pneumonia following influenza virus infection is associated with high mortality, but the mechanism is largely unknown. Epigenetic gene regulation appears to play key roles in innate and adaptive immunity. We hypothesized that histone acetylation, a major epigenetic mechanism associated with transcriptionally active chromatin, might contribute to the poor outcome of postinfluenza pneumonia. DESIGN: Prospective experimental study. SETTING: University research laboratory. SUBJECTS: C57BL/6 male mice. INTERVENTIONS: Mice were infected intranasally with 1.0 × 10 colony-forming units of Streptococcus pneumoniae, 7 days after intranasal inoculation with five plaque-forming units of influenza virus A/H1N1/PR8/34. The mice were intraperitoneally injected with the histone deacetylase inhibitor trichostatin A (1 mg/kg) or vehicle once a day from 1 hour after pneumococcal infection throughout the course of the experiment. The primary outcome was survival rate. MEASUREMENTS AND MAIN RESULTS: Trichostatin A significantly suppressed histone deacetylase activity and significantly improved the survival rate of mice (56.3%) after postinfluenza pneumococcal infection when compared with vehicle-treated mice (20.0%), which was associated with a significant decrease in the total cell count of the bronchoalveolar lavage fluid. The interleukin-1ß level in the serum and the number of natural killer cells in the lungs were significantly lower in the trichostatin A-treated group. CONCLUSIONS: The histone deacetylase inhibitor trichostatin A protects mice against postinfluenza pneumonia possibly through multiple factors, including decreasing local cell recruitment into the lungs and suppressing systemic inflammation.

Health-related quality of life is inversely correlated with C-reactive protein and age in Mycobacterium avium complex lung disease: a cross-sectional analysis of 235 patients.

BACKGROUND: Mycobacterium avium complex (MAC) lung diseases generally cause chronic disease in immunocompetent hosts. Although a few studies have examined health-related quality of life (HRQL) in patients with MAC lung disease, there have been no large studies. This study aimed to evaluate HRQL and its correlation with clinical outcomes in MAC lung disease. METHODS: A cross-sectional study was conducted at Keio University Hospital to investigate the factors associated with HRQL in pulmonary nontuberculous mycobacterial diseases. MAC lung diseases were diagnosed according to the 2007 ATS/IDSA guidelines for nontuberculous mycobacterial diseases. The 36-item short form health survey (SF-36) was administered to assess clinical outcomes. Clinical variables included treatment status, latest haematological data, and bacterial smear and culture results. RESULTS: The SF-36 scores for the 235 patients (median age, 69 years; 45 men and 190 women) with MAC lung disease, except for the bodily pain and mental health subscale scores, were significantly lower than the Japanese population norms. In the multivariable analyses, current treatment for MAC and a positive sputum smear or culture within the past year were significantly associated with lower SF-36 scores. C-reactive protein (CRP) and age showed stronger inverse correlations with SF-36 scores. CONCLUSIONS: HRQL, especially the physical component, was impaired in patients with MAC lung diseases; this appears to be related with current treatment status, positive sputum smear or culture within the previous year, and particularly CRP and age. Further studies including qualitative assessments are needed to investigate the efficacy of CRP as a marker for progression or treatment response in MAC lung disease. TRIAL REGISTRATION: Clinical trial registered with UMIN ( UMIN000007964 ).

Levels of Soluble Receptor for Advanced Glycation End Products in Bronchoalveolar Lavage Fluid in Patients with Various Inflammatory Lung Diseases.

Receptor for advanced glycation end products (RAGE) is a multiligand receptor of S100/calgranulins, high-mobility group box 1, and others, and it is associated with the pathogenesis of various inflammatory and circulatory diseases. The soluble form of RAGE (sRAGE) is a decoy receptor and competitively inhibits membrane-bound RAGE activation. In this study, we measured sRAGE levels in bronchoalveolar lavage fluid (BALF) of 78 patients, including 41 with interstitial pneumonia, 11 with sarcoidosis, 9 with respiratory infection, 7 with ARDS, 5 with lung cancer, and 5 with vasculitis. Among them, sRAGE was detectable in BALF of 73 patients (94%). In patients with ARDS and vasculitis, the sRAGE levels were significantly higher than in the control subjects and those with interstitial pneumonia. The sRAGE levels were positively correlated with total cell counts in BALF and serum levels of surfactant protein-D, lactate dehydrogenase, and C-reactive protein. There was an inverse correlation between PaO2/FIO2 ratio and sRAGE levels. These results indicate that sRAGE in BALF might be considered as a biomarker of lung inflammatory disorders, especially ARDS and vasculitis.

Pulmonary nocardiosis caused by Nocardia cyriacigeorgica in patients with Mycobacterium avium complex lung disease: two case reports.

BACKGROUND: Pulmonary nocardiosis frequently occurs in immunocompromised hosts and in some immunocompetent hosts with chronic lung disease; however, few reports have described pulmonary nocardiosis with nontuberculous mycobacterial lung infection. Here we report for the first time two cases of pulmonary nocardiosis caused by Nocardia cyriacigeorgica associated with Mycobacterium avium complex (MAC) lung disease caused by M. avium. CASE PRESENTATION: Case 1 is that of a 72-year-old Japanese man with untreated MAC lung disease, who was diagnosed with rheumatoid arthritis and initiated on methotrexate. After 3 years of methotrexate therapy, the patient remained smear-negative and culture-positive for MAC, but also became smear-positive for Nocardia species. He received trimethoprim/sulfamethoxazole, and his symptoms and lung infiltrates improved. Case 2 is that of an immunocompetent 53-year-old Japanese woman with MAC lung disease, who was treated with a combined therapy of clarithromycin, rifampicin, ethambutol, and levofloxacin. MAC sputum culture was negative after 1 year of combined treatment, which was maintained for 2 years. After four treatment-free years, Nocardia species were occasionally isolated from her sputum, although MAC was rarely isolated from sputum cultures over the same period. In both cases, the Nocardia species were identified as the recently defined N. cyriacigeorgica by 16S ribosomal RNA gene sequencing. CONCLUSION: We report two cases of pulmonary nocardiosis caused by N. cyriacigeorgica associated with MAC lung disease caused by M. avium and suggest that N. cyriacigeorgica may be a major infective agent associated with MAC lung disease.