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).

Measurement of dyspnea in patients with obstructive sleep apnea.

PURPOSE: Patients with obstructive sleep apnea (OSA) frequently complain of exertional dyspnea. We aimed to assess its related factors and the significance of its measurement in OSA. METHODS: We evaluated 301 subjects with suspected OSA for dyspnea during activities of daily living using the Medical Research Council (MRC) scale. We analyzed the relationships between MRC grades and various subjective and objective indices. Further, the relationship of disease severity based on the apnea/hypopnea index (AHI) with these indices was examined. Results were compared between those obtained using MRC grades and the AHI. RESULTS: Of 301 subjects, 265 were diagnosed with OSA. Their MRC scores were worse than in non-OSA patients. Among OSA patients, 125 had MRC grade 1 (mild), 121 had MRC grade 2 (moderate), and 19 had MRC grade 3 or more (severe) dyspnea. Various measurements differed significantly between groups categorized according to the MRC scale although determinants between mild and moderate groups and between moderate and severe groups differed. AHI categorizations were not significantly related to patient-reported measurements such as the Medical Outcomes Study 36-item short form, Pittsburgh Sleep Quality Index, and Hospital Anxiety and Depression Scale scores, unlike categorization based on the MRC scale. CONCLUSIONS: Dyspnea is an important outcome in OSA although dyspnea in OSA patients is unrelated to the sleep disorder per se. Measurement of dyspnea in patients with OSA might provide further insights into the health of these patients and clinical manifestations of this disease.

Analysis of anatomical and functional determinants of obstructive sleep apnea.

PURPOSE: Craniofacial abnormalities have an important role in the occurrence of obstructive sleep apnea (OSA) and may be particularly significant in Asian patients, although obesity and functional abnormalities such as reduced lung volume and increased airway resistance also may be important. We conducted simultaneous analyses of their interrelationships to evaluate the relative contributions of obesity, craniofacial structure, pulmonary function, and airway resistance to the severity of Japanese OSA because there are little data in this area. METHODS: A cross-sectional observational study was performed on 134 consecutive Japanese male patients. A sleep study, lateral cephalometry, pulmonary function tests, and impulse oscillometry (IOS) were performed on all patients. RESULTS: Age, body mass index (BMI), position of the hyoid bone, and proximal airway resistance on IOS (R20) were significantly related to the apnea/hypopnea index (AHI) (p < 0.05) in multiple regression analysis. Subgroup analysis showed that, for moderate-to-severe OSA (AHI ≥ 15 events/h), neck circumference and R20 were predominantly related to AHI, whereas for non-to-mild OSA (AHI < 15 events/h), age and expiratory reserve volume were the predominant determinants. In obese subjects (BMI ≥ 25 kg/m(2)), alveolar-arterial oxygen tension difference, position of the hyoid bone, and R20 were significantly associated with AHI, whereas age alone was a significant factor in nonobese subjects (BMI < 25 kg/m(2)). CONCLUSIONS: Aside from age and obesity, anatomical and functional abnormalities are significantly related to the severity of Japanese OSA. Predominant determinants of AHI differed depending on the severity of OSA or the magnitude of obesity.

Effectiveness of high-flow nasal cannula on pulmonary rehabilitation in subjects with chronic respiratory failure.

BACKGROUND: The effects of exercise training using both high fraction of inspired oxygen (FIO2) and high flow oxygen delivered through a high-flow nasal cannula (HFNC) on exercise capacity in patients with chronic respiratory failure (CRF) receiving long-term oxygen therapy (LTOT) are unknown. METHODS: In this randomized study, 32 patients with CRF receiving LTOT were assigned to undergo 4 weeks of exercise training on a cycle ergometer using an HFNC (flow: 50 L/min) with a FIO2 of 1.0 (HFNC group; n = 16) or ordinary supplemental oxygen via a nasal cannula (flow: 6 L/min) (oxygen group; n = 16). A 6-min walking test and a constant-load test were performed before and after 4 weeks of exercise training. RESULTS: Following 4 weeks of exercise training, change in the 6-min walking distance was significantly greater in the HFNC than in the oxygen group (55.2 ± 69.6 m vs. -0.5 ± 87.3 m; p = 0.04). However, there was no significant difference between the two groups in the degree of improvement in the duration of the constant-load exercise test after exercise training. CONCLUSIONS: Considering the effect on daily activities (e.g., walking), exercise training using both high FIO2 and high flow through an HFNC is a potentially superior exercise training modality for patients with CRF receiving LTOT. Clinical Trial Registration - http://www. CLINICALTRIALS: gov. Unique identifier: NCT02804243.

Multimodal Telemonitoring for Weight Reduction in Patients With Sleep Apnea: A Randomized Controlled Trial.

BACKGROUND: Telemonitoring the use of CPAP devices and remote feedback on device data effectively optimizes CPAP adherence in patients with OSA. RESEARCH QUESTION: Can expanding the scope of telemonitoring and remote feedback to body weight (BW), BP, and physical activity enhance efforts for BW reduction in Patients with OSA receiving CPAP? STUDY DESIGN AND METHODS: Participants were recruited from patients at 16 sleep centers in Japan with OSA and obesity who were receiving CPAP therapy. Obesity was defined as a BMI of ≥ 25 kg/m2, based on Japanese obesity guidelines. Implementation of CPAP telemonitoring was enhanced with electronic scales, BP monitors, and pedometers that could transmit data from devices wirelessly. Participants were randomized to the multimodal telemonitoring group or the usual CPAP telemonitoring group and were followed up for 6 months. Attending physicians provided monthly telephone feedback calls to the usual CPAP telemonitoring group on CPAP data obtained remotely. In the multimodal telemonitoring group, physicians additionally encouraged participants to reduce their BW, after sharing the remotely obtained data on BW, BP, and step count. The primary outcome was set as ≥ 3% BW reduction from baseline. RESULTS: One hundred sixty-eight participants (BMI, 31.7 ± 4.9 kg/m2) completed the study, and ≥ 3% BW reduction occurred in 33 of 84 participants (39.3%) and 21 of 84 participants (25.0%) in the multimodal telemonitoring and usual CPAP telemonitoring groups, respectively (P = .047). Whereas no significant differences were found between the two groups in the change in office and home BP, daily step counts during the study period were significantly higher in the multimodal telemonitoring group than in the usual CPAP telemonitoring group (4,767 steps/d [interquartile range (IQR), 2,864-6,617 steps/d] vs 3,592 steps/d [IQR, 2,117-5,383 steps/d]; P = .02) INTERPRETATION: Multimodal telemonitoring may enhance BW reduction efforts in patients with OSA and obesity. TRIAL REGISTRY: UMIN Clinical Trials Registry; No.: UMIN000033607; URL: www.umin.ac.jp/ctr/index.htm.

Immediate noninvasive ventilation may improve mortality in patients with hepatopulmonary syndrome after liver transplantation.

Hepatopulmonary syndrome (HPS) is defined as hypoxemia induced by intrapulmonary vascular dilations associated with liver disease. Although liver transplantation (LT) is the only effective therapy established for severe HPS, patients with a partial pressure of arterial oxygen (PaO(2) ) less than 60 mm Hg have a poor prognosis. We treated a 4-year-old boy with HPS whose preoperative PaO(2) level was 48.8 mm Hg. After LT, he had persistent severe hypoxemia, although he was receiving high-flow oxygen. Noninvasive ventilation (NIV) was introduced, and his respiratory insufficiency promptly improved. Therefore, NIV therapy immediately after extubation following transplantation was administered to the next 4 consecutive HPS patients whose preoperative PaO(2) was less than 60 mm Hg. The NIV treatment of these 5 patients could have been responsible for preventing severe postoperative complications as well as reintubation and hospital death. NIV therapy for both pediatric and adult patients with severe HPS immediately after extubation might protect them from severe hypoxemia after transplantation and from complications necessitating reintubation and might improve their prognosis.

[Pneumonitis induced by rifampicin].

An 86-year-old male with pulmonary tuberculosis developed fever, rash, and interstitial pneumonia 3 weeks after the beginning of treatment with isoniazid (INH), rifampicin (RFP), and ethambutol (EB). Chest CT showed new infiltration shadows that were diffuse bilateral ground-glass opacities mixed with dense consolidation and septal thickening, accompanied by a small amount of pleural effusion. Drug-induced pneumonitis was suspected, and therefore the antituberculous regimen was discontinued. The radiologic findings and symptoms improved promptly. A provocation trial with RFP lead to fever, diarrhea, and rash. Therefore, RFP was considered to be the causative drug. INH and EB were reintroduced without any recurrence of the symptoms. Clinicians should be aware not only of paradoxical reactions but also of drug-induced pneumonitis, when a new pulmonary infiltrate develops in the course of tuberculosis treatment.

The use of non-invasive ventilation for life-threatening asthma attacks: Changes in the need for intubation.

BACKGROUND AND OBJECTIVE: Although non-invasive ventilation (NIV) has been shown to be effective in a wide variety of respiratory diseases, its role in severe asthma attacks remains uncertain. The aim of this study was to clarify the effectiveness of NIV in patients experiencing severe attacks of asthma. METHODS: A retrospective cohort study was performed, comparing the periods November 1999-October 2003 (pre-introduction of NIV) and November 2004-October 2008 (post-introduction of NIV). The data and clinical outcomes for patients who experienced severe attacks of asthma, and who fulfilled the inclusion criteria, were retrieved and compared. RESULTS: Fifty events (48 patients) from the pre-NIV period and 57 events (54 patients) from the post-NIV period, which required hospitalization, were included in the analysis. Nine of the 50 pre-NIV events (mean PaO(2)/fraction of inspired O(2) (FiO(2)) 241 +/- 161; PaCO(2) 79 +/- 40) were treated primarily by endotracheal intubation (ETI), while 17 of the 57 post-NIV events (PaO(2)/FiO(2) 197 +/- 132, P = 0.39; PaCO(2) 77 +/- 30, P = 0.95) were treated primarily by NIV. The rate of ETI decreased in the post-NIV period (2/57 (3.5%) vs 9/50 (18%), P = 0.01). NIV was started earlier than mechanical ventilation (MV) with ETI (mean time interval between arrival and start of MV 171.7 +/- 217.9 min vs 38.5 +/- 113.8 min for NIV, P < 0.05). In the post-NIV cohort, there was a trend towards a reduction in the duration of MV with ETI or NIV (36.9 +/- 38.4 h vs 20.3 +/- 35.8 h, P = 0.09), and hospital stay was shortened (12.6 +/- 4.2 vs 8.4 +/- 2.8 days, P < 0.01). No deaths occurred during this period as a consequence of asthma attacks. CONCLUSIONS: The need for ETI in patients with severe attacks of asthma was decreased after introduction of NIV. The ready availability of NIV enabled the rapid commencement of MV and may decrease the need for ETI. NIV is an acceptable and useful method of stabilizing patients experiencing severe attacks of asthma.

[A case of squamous cell lung carcinoma with gastric metastasis diagnosed by gastroendoscopic biopsy].

A 59-year-old man was referred to our hospital due to of a right pulmonary hilar mass shadow found on a chest X-ray film in October 2008. Bronchoscopy and transbronchial biopsy at that time revealed squamous cell carcinoma. The clinical stage was IIIB (T4N2M0). He was readmitted 2 months later because of appetite loss and severe anemia. An abdominal CT scan showed thickening of the stomach wall. Gastroendoscopy showed a submucosal tumor with central depression in the middle body of the stomach. We histologically confirmed that the gastric lesion was metastasis from the squamous cell lung carcinoma. Here we report a rare case of squamous cell lung carcinoma with gastric metastasis diagnosed by gastroendoscopic biopsy while the patient was alive.

A Randomized Controlled Trial of Telemedicine for Long-Term Sleep Apnea Continuous Positive Airway Pressure Management.

Rationale: The effects of telemedicine on adherence in patients with obstructive sleep apnea with long-term continuous positive airway pressure (CPAP) use have never been investigated.Objectives: To examine effects of a telemedicine intervention on adherence in long-term CPAP users.Methods: In a prospective, randomized, multicenter noninferiority trial conducted in 17 sleep centers across Japan, patients who had used CPAP for >3 months and were receiving face-to-face follow-up by physicians every 1 or 2 months were randomized by a coordinating center in a blind manner to the following three groups: 1) follow-up every 3 months accompanied by a monthly telemedicine intervention (telemedicine group: TM-group), 2) follow-up every 3 months (3-month group: 3M-group), or 3) monthly follow-up (1-month group: 1M-group). Each group was followed up for 6 months. The change in percentage of days with ≥4 h/night of CPAP use from baseline to the end of the study period was evaluated. A decline of ≥5% from baseline was considered deterioration of adherence. Noninferiority of TM- and 3M-groups compared with the 1M-group according to the number of patients with deterioration of adherence was evaluated with the Farrington and Manning test (noninferiority margin 15%).Results: A total of 483 patients were analyzed (median duration of CPAP use, 29 [interquartile range, 12-71] mo), and deterioration of adherence was found in 41 of 161 (25.5%), 55 of 166 (33.1%), and 35 of 156 (22.4%) patients in the TM-, 3M-, and 1M-groups, respectively. The noninferiority of the TM-group compared with the 1M-group was verified (difference in percentage of patients with adherence deterioration, 3.0%; 95% confidence interval [CI], -4.8% to 10.9%; P < 0.01). Conversely, the 3M-group did not show noninferiority to the 1M-group (percentage difference, 10.7%; 95% CI, 2.6% to 18.8%; P = 0.19). In the stratified analysis, adherence in TM- and 1M-group patients with poor adherence at baseline improved (TM: 45.8% ± 18.2% to 57.3% ± 24.4%; P < 0.01; 1M: 43.1% ± 18.5% to 53.6% ± 24.3%; P < 0.01), whereas that of the 3M-group did not (39.3% ± 20.8% to 39.8% ± 24.8%; P = 0.84).Conclusions: Intensive telemedicine support could help to optimize CPAP adherence even after long-term CPAP use.Clinical trial registered with www.umin.ac.jp/ctr/index.htm (trial number: UMIN000023118).

Low Levels of PaO2 after Long-term Noninvasive Ventilation are a Poor Prognostic Factor in Patients with Restrictive Thoracic Disease.

Objective The effects of partial pressure of arterial oxygen (PaO2) after introducing long-term noninvasive ventilation (NIV) on the prognosis of patients with restrictive thoracic disease and chronic respiratory failure are not exactly known. Methods Data from 141 patients with restrictive thoracic disease under long-term nocturnal NIV were retrospectively examined. We divided the patients into 2 groups according to the daytime PaO2 value while breathing spontaneously with prescribed oxygen at 12 months after introducing NIV: PaO2≥80 Torr group (n=76) and PaO2<80 Torr group (n=65). Results During the 4-year follow-up, the mortality was significantly higher in the PaO2<80 Torr group than in the PaO2≥80 Torr group (50.8% vs. 32.9%, p=0.03). Independent factors associated with the 4-year mortality after introducing NIV determined by a multivariate logistic regression analysis were a low body mass index [odds ratio (OR) 0.87; 95% confidence interval (CI) 0.77 to 0.97; p=0.01], assisted mode with NIV (OR 4.11; 95% CI, 1.79 to 9.45; p=0.0009), hospitalization during the first year of introducing NIV (OR 1.72; 95% CI, 1.06 to 2.79; p=0.03), and daytime PaO2<80 Torr at 12 months after introducing NIV (OR 2.30; 95% CI, 1.03 to 5.10; p=0.04). Conclusion A low daytime PaO2 at 12 months after introducing NIV was an independent risk factor for mortality. Keeping the daytime PaO2≥80 Torr through the adjustment of the nocturnal NIV settings or increased diurnal supplemental oxygen may help improve the prognosis in patients with restrictive thoracic disease who are under NIV.

Acylated ghrelin level in patients with OSA before and after nasal CPAP treatment.

BACKGROUND AND OBJECTIVE: Patients with newly diagnosed OSA have been reported to have recent weight gain prior to diagnosis. Ghrelin stimulates food intake and increases weight gain. Plasma ghrelin is decreased in obese and increased in lean individuals. Of the two circulating forms of ghrelin, acylated and unacylated, the former is thought to be essential for the biological activity of ghrelin. METHODS: The plasma levels of the two forms of ghrelin were measured in 21 OSA patients (with a mean of 46.2 sleep-disordered events/h) before and after 1 month of nasal CPAP (nCPAP) treatment, and were compared with those in 14 untreated OSA patients and 13 individuals without OSA. RESULTS: The BMI was significantly higher in the 21 OSA patients than in the non-OSA group as were the baseline acylated (11.4 +/- 5.86 vs 7.19 +/- 3.80 fmol/mL, P = 0.03) and unacylated (84.2 +/- 50.6 vs 48.3 +/- 23.2 fmol/mL, P = 0.02) ghrelin levels. The total ghrelin level was positively correlated with the number of sleep-disordered breathings (P = 0.002). After 1 month of nCPAP treatment, the acylated ghrelin level significantly decreased (P = 0.02) while the unacylated ghrelin level did not (P = 0.09). CONCLUSIONS: Treatment of OSA may play an important role in the management of obesity in these patients by reducing the acylated ghrelin level.

Validation of the Japanese Severe Respiratory Insufficiency Questionnaire in hypercapnic patients with noninvasive ventilation.

BACKGROUND: The Severe Respiratory Insufficiency (SRI) Questionnaire was originally developed in German to assess health-related quality of life (HRQL) and was validated as a multidimensional instrument with high psychometric properties in chronic hypercapnic respiratory failure (CHRF) patients receiving noninvasive ventilation (NIV). We aimed to investigate the intercultural adaptation of the Japanese SRI Questionnaire and whether it is a reliable and valid HRQL questionnaire to administer to those patients. METHODS: The SRI Questionnaire was adapted to Japanese using a translation and back-translation procedure, followed by equivalency assessment. It was validated in 56 stable outpatients receiving NIV for CHRF, primarily due to chronic obstructive pulmonary disease (COPD) and/or pulmonary tuberculosis sequelae. RESULTS: Examination of the frequency distribution of the Japanese SRI Questionnaire showed that the subscales and summary were approximately normally distributed and well balanced. There were no significant differences in SRI scores between patients with COPD and pulmonary tuberculosis sequelae. Cronbach׳s α values representing internal consistency of seven SRI subscales ranged from 0.56 to 0.80; attendant symptoms and sleep had the lowest values. Cronbach׳s α value was 0.92 for the SRI summary. The SRI summary score was significantly related to all eight subscales of the Medical Outcomes Study 36-item short form, with correlation coefficients of 0.41-0.66. CONCLUSIONS: The Japanese SRI Questionnaire was produced using a standardized procedure and an equivalency study. It has high psychometric properties with internal consistency and concurrent validity. The Japanese SRI Questionnaire can be used to assess HRQL in patients on NIV for CHRF.

Comparison of Different Disease-Specific Health-Related Quality of Life Measurements in Patients with Long-Term Noninvasive Ventilation.

BACKGROUND: Two disease-specific questionnaires have been developed to assess health-related quality of life (HRQL) in patients with chronic respiratory failure: the Severe Respiratory Insufficiency (SRI) Questionnaire and the Maugeri Respiratory Failure (MRF) Questionnaire. We aimed to compare the characteristics of the SRI, MRF-26, and St. George's Respiratory Questionnaire (SGRQ) for use in patients with home noninvasive ventilation (NIV). METHODS: Fifty-six outpatients receiving long-term NIV were recruited and underwent assessments of pulmonary function, arterial blood gas, HRQL, dyspnea, and psychological status. RESULTS: Correlations of the SRI and MRF-26 with the SGRQ were modest. While pulmonary function was weakly related to only some domains of the SRI and MRF-26, the modified Medical Research Council (mMRC) dyspnea scale and Hospital Anxiety and Depression Scale (HADS) were significantly related to all domains of the SRI and MRF-26. Multiple regression analyses showed that HADS depression and mMRC accounted for 34% and 27% of the variance in the SRI, 24% and 37% in the MRF-26, and 17% and 46% in the SGRQ, respectively. CONCLUSIONS: The SRI and MRF-26 were reliable questionnaires for patients receiving long-term NIV. Dyspnea and psychological status were their main common determinants. The SRI covers more psychological health impairments than the MRF. This trial is registered with ClinicalTrials.gov Identifier: NCT00905476.

Analysis of the relationship between health status and mortality in hypercapnic patients with noninvasive ventilation.

BACKGROUND: Health status and mortality are important outcomes in patients with advanced pulmonary diseases receiving noninvasive ventilation (NIV). However, their relationship has not been thoroughly investigated. METHODS: The present study prospectively recruited 56 stable outpatients treated with NIV for chronic hypercapnic respiratory failure caused by chronic obstructive pulmonary disease and/or pulmonary tuberculosis sequelae. At baseline, health status was measured by the Medical Outcomes Study 36-item short form, a generic questionnaire; the St. George's Respiratory Questionnaire (SGRQ), a respiratory-specific questionnaire; and two respiratory failure-specific questionnaires, the Maugeri Respiratory Failure questionnaire and the Severe Respiratory Insufficiency (SRI) questionnaire. Arterial blood gas, pulmonary function, dyspnea and psychological status were also measured. RESULTS: In cross-sectional comparisons of the four health status questionnaires, the SGRQ and SRI questionnaire had lower floor and ceiling effects. During the 3-year follow-up, 16 patients (29%) died. Health status shown by the SGRQ and SRI was significantly predictive of mortality, independently of the physiological measures of low body mass index (BMI), hypercapnia, and low pulmonary function. Stepwise multivariate analyses indicated that the SRI summary score was the most significant predictor of mortality (P = 0.0006) followed by BMI (P = 0.012). CONCLUSION: There was a significant relationship between health status and 3-year mortality in patients with NIV, independently of under-nutrition, hypercapnia and low pulmonary function. Health status measurement is important not only to comprehensively evaluate disease severity in relation to its close association with mortality, but also to elucidate factors that improve the survival of patients with advanced respiratory diseases.

[Noninvasive positive pressure ventilation in patients with acute exacerbations of pulmonary tuberculosis sequelae].

To clarify whether noninvasive positive pressure ventilation (NPPV) is effective in patients with acute exacerbations of pulmonary tuberculosis sequelae (PTS), 50 PTS patients (66 episodes) without long-term domiciliary noninvasive ventilation were studied, retrospectively. The average values (SD) of their pulmonary function tests and arterial blood gases were as follows; %predicted VC = 31.4 (8.4)%, pH = 7.29 (0.06), PaCO2 = 91.8 (19.7) mmHg, and PaO2 = 64.2 (20.3) mmHg. The probability of avoiding endotracheal intubation and recovering from an acute exacerbation with NPPV (NPPV success rate) was 92% as a whole. NPPV success rates according to the causes of deterioration were as follows; 96% in 26 episodes with only a simple right heart failure, 93% in 29 episodes with airway infectious diseases, 75% in eight episodes with pneumonia and/or acute respiratory distress syndrome. Moreover, the NPPV success rate of eight episodes in coma or semicoma was 88%. Most patients were treated in respiratory wards rather than intensive care units. Out of 46 patients who recovered from an acute exacerbation, 41 finally received domiciliary NPPV. In facilities where staff are well-trained for an acute NPPV, patients with exacerbations of PTS can be treated as successfully with NPPV as patients with COPD.

Successful desensitization therapy for a patient with isoniazid-induced hypersensitivity pneumonia.

A 57-year-old male was diagnosed with mycobacterium tuberculoma and was treated with isoniazid, rifampicin, ethambutol, and pyrazinamide. Three weeks after initiation of treatment, he presented with fever and appetite loss. Chest radiograph showed diffuse micronodular shadows on both lung fields. High-resolution chest computed tomography findings were diffuse parenchymal micronodules in both lungs, which was consistent with hypersensitivity pneumonia. Because drug-induced pneumonia was suspected, the antituberculous regimen was discontinued. The symptoms and diffuse micronodular shadows improved. A drug lymphocyte stimulation test was only positive for isoniazid, so we suspected that the pneumonia was induced by isoniazid. Rifampicin and ethambutol were reintroduced without any recurrence of the abnormal shadows. Next, we tried desensitization to isoniazid over a period of two weeks, which was successful without any adverse events. Although isoniazid-induced pneumonia is extremely rare, it is important to recognize that isoniazid can cause such an adverse reaction. In addition, drug desensitization may be useful in drug-induced pneumonia.

The Importance of Stabilizing PaCO2 during Long-term Non-invasive Ventilation in Subjects with COPD.

OBJECTIVE: In subjects with chronic obstructive pulmonary disease (COPD), the effect of partial pressure of CO2 (PaCO2) alterations during long-term non-invasive ventilation (NIV) on continuance remains uncertain. We herein investigated the utility of PaCO2 stability during long-term NIV as a prognostic outcome. METHODS: We retrospectively assessed data from 54 subjects with COPD who received long-term NIV. The annual alteration in PaCO2 during NIV was determined using a simple linear regression method for each subject who had at least two 6-month intervals of PaCO2 data. Annual alterations in PaCO2 during long-term NIV and probable confounders were examined, and long-term NIV discontinuation was the major outcome. RESULTS: Data from 37 subjects who met the criteria were analyzed. PaCO2 during long-term NIV increased slightly in 19 subjects (group 1, <2 mm Hg/y), and increased greatly in 18 subjects (group 2, >2 mmHg/y). In the multivariate modality model, smaller annual alterations in PaCO2 (p=0.009) and lower PaCO2 6 months after the start of long-term NIV (6 m-PaCO2) (p=0.03) were associated with a significantly higher probability of continuing NIV. The 2- and 5-year probabilities of continuing NIV were 89% and 66% for group 1 and 78% and 32% for group 2, respectively. CONCLUSION: A lower 6 m-PaCO2 and a lower annual alteration of PaCO2 during long-term NIV are significant predictive variables for patients with COPD.

[Evaluation of the Mycobacteria Growth Indicator Tube system for detection and quantification of mycobacteria from clinical specimens].

The Mycobacteria Growth Indicator Tube (MGIT) system, a broth system for detection of mycobacterial growth, has been shown to be more sensitive and rapid compared with the egg-based Ogawa solid media, while the lack of ability to quantitate bacterial growth is the problem. We compared mycobacterial growth in the MGIT and the Ogawa systems, and evaluated the relationship between detection time in the MGIT system and bacterial CFU on Ogawa egg medium. A total of 413 respiratory specimens from 245 patients were included in the study, of which Mycobacterium tuberculosis (MTB), M. avium complex (MAC) and M. kansasii were recovered from 127, 42 and 6 specimens, respectively. Recovery rates were significantly higher and detection time was significantly shorter in the MGIT than in the Ogawa for MTB and MAC. Detection time in the MGIT was significantly shorter in smear positive specimens than in smear negative ones for MTB and MAC. There was a significant negative correlation between CFUs on Ogawa egg medium and detection time in the MGIT system for the MTB, therefore, this system may have an ability to quantitate live mycobacteria according to the detection time.

The importance of controlling PaCO2 throughout long-term noninvasive ventilation.

BACKGROUND: The significance of changes in P(aCO2) during long-term noninvasive ventilation (NIV) on prognosis remains unclear. We aimed to clarify whether stabilizing P(aCO2) during NIV had a favorable prognostic effect. METHODS: Data from 190 subjects with restrictive thoracic disease and who received long-term NIV were studied retrospectively. The annual change in P(aCO2) during NIV was determined using a simple linear regression method for each subject who had at least 4 6-month intervals of P(aCO2) data. Annual changes in P(aCO2) during long-term NIV and possible confounders were analyzed with discontinuation of long-term NIV as the main outcome. RESULTS: One hundred and twenty-five subjects who had > 4 6-month intervals of P(aCO2) data were included in the study. P(aCO2) during long-term NIV decreased in 41 subjects (group 1; < 0 mm Hg/y), increased slightly in 42 subjects (group 2; between 0 and 1.85 mm Hg/y), and increased significantly in 42 subjects (group 3; > 1.85 mm Hg/y). Smaller annual changes in P(aCO2) (P < .001) and a control ventilator mode (P = .008) were associated with a significantly higher probability of continuing NIV, compared with decreased P(aCO2) 3-6 months after the start of long-term NIV (P = .11). The 10-y probability of continuing NIV was 69% in group 1, 39% in group 2, and 12% in group 3. CONCLUSIONS: A decrease in the annual change of P(aCO2) during long-term NIV was shown to be a significantly prognostically favorable factor. Efforts to reduce P(aCO2) should be made if P(aCO2) increases at a greater rate during long-term NIV.