Clinical course of COPD patients with exercise-induced elevation of pulmonary artery pressure or less severe pulmonary hypertension presenting with respiratory symptoms and the impact of bosentan intervention-prospective, single-center, randomized, parallel-group study.

BACKGROUND: The data on bosentan were lacking for the treatment of exercise-induced elevation of pulmonary artery pressure (eePAP) or less severe PH in COPD. This study was conducted to investigate long-term efficacy and safety of bosentan for the treatment of eePAP or less severe PH in COPD. METHODS: COPD patients diagnosed at this hospital as having COPD (WHO functional class II, III or IV) with eePAP or less severe PH whose respiratory symptoms were stable but remained and gradually progressed even after COPD therapy were randomly assigned in a 1:1 ratio to receive either bosentan or no PH treatment for two years and assessed at baseline and every 6 months for respiratory failure, activities of daily living (ADL), lung and heart functions by right heart catheterization (RHC), and other parameters. RESULTS: A total of 29 patients who underwent RHC for detail examination were enrolled in the current study between August 2010 and October 2018.No death occurred in drug-treated group (n = 14) for 2 years; 5 patients died in untreated group (n = 15). Significant differences were noted between the 2 group in hospital-free survival (686.00 ± 55.87 days vs. 499.94 ± 53.27 days; hazard ratio [HR], 0.18; P = 0.026) and overall survival (727 days vs. 516.36 ± 55.38 days; HR, 0.095; P = 0.030) in all causes of death analysis, but not in overall survival in analysis of respiratory-related death. Bosentan was not associated with increased adverse events including requiring O2 inhalation. CONCLUSIONS: This study suggested that the prognosis for COPD patients with eePAP or less severe PH presenting with respiratory symptoms was very poor and that bosentan tended to improve their prognosis and suppress ADL deterioration without worsening respiratory failure. TRIAL REGISTRATION: This study was registered with UMIN-CTR Clinical Trial as UMIN000004749 . First trial registration at 18/12/2010.

Usefulness of simultaneous impulse oscillometry and spirometry with airway response to bronchodilator in the diagnosis of asthmatic cough.

Objective: Some of the most common causes of chronic cough include cough variant asthma (CVA), bronchial asthma (BA), and asthma-COPD overlap (ACO). Although there is some overlap in the etiology of these diseases, it is clinically important to attempt an early differential diagnosis due to treatment strategies and prognoses.Methods: Spirometry and impulse oscillometry (IOS) before and after bronchodilator inhalation were analyzed for clinically diagnosed CVA (cCVA, n = 203), BA (cBA, n = 222), and ACO (cACO, n = 61).Results: A significant difference in ΔFEV1 was observed between cBA and cCVA (ΔFEV1 improvement of 122.5 mL/5.4% and 65.7 mL/2.2%, respectively), but no difference was observed in ΔPEF, ΔV50, or ΔV25. Except for R20 (resistance at 20 Hz), significant differences between the three groups were observed in IOS. In IOS, cCVA and cBA showed comparable peripheral airway response to bronchodilator which was thought to be commensurate with changes in V50 and V25. cACO improved ΔFEV1 improvement of 81.0 mL/6.2% and was distinguished by a downward respiratory system reactance (Xrs) waveform with a limited bronchodilator response. FEV1/FVC, %FEV1, and %V25 had relatively strong correlations with the three IOS parameters, X5 (reactance at 5 Hz), resonant frequency (Fres), and low-frequency reactance area (ALX), in the correlation between IOS and spirometers.Conclusion: Changes in IOS parameters were more sensitive in this study than changes in FEV1 or the flow-volume curve. Considering the benefits and relevance of the two different tests, simultaneous IOS and spirometry testing were useful in the diagnosis of asthmatic cough.

Potential benefit of bosentan therapy in borderline or less severe pulmonary hypertension secondary to idiopathic pulmonary fibrosis-an interim analysis of results from a prospective, single-center, randomized, parallel-group study.

BACKGROUND: No drugs have been approved for the treatment of patients with pulmonary hypertension (PH) secondary to idiopathic pulmonary fibrosis (IPF), particularly those with idiopathic honeycomb lung. This study was conducted to investigate the long-term efficacy and safety of bosentan for PH based on changes in prognosis and respiratory failure. METHODS: IPF patients with borderline or less severe PH and completely organized honeycomb lung were randomized (1:1) to bosentan or no treatment for PH for 2 years and assessed at baseline and every 6 months for respiratory failure, activities of daily living (ADL), lung and heart functions by right cardiac catheterization, and other parameters. An interim analysis was performed, however, following detection of a significant survival benefit favoring bosentan therapy. RESULTS: Significant differences were noted for the bosentan-treated (n = 12) vs. untreated (n = 12) groups in hospital-free survival (603.44 ± 50.074 days vs. 358.87 ± 68.65 days; hazard ratio [HR], 0.19; P = 0.017) and overall survival (671 days vs. 433.78 ± 66.98 days; HR, 0.10; P = 0.0082). Again, significant improvements were noted for the bosentan-treated group from baseline to month 6 or 12 in several indices in ADL, pulmonary circulation, and %DLCO. Without requiring O2 inhalation, bosentan was associated with no increase but a trend toward a decrease in adverse events and an improvement in respiratory status. CONCLUSIONS: Bosentan tended to improve prognosis and ADL without worsening respiratory failure in IPF patients with borderline or less severe PH and completely organized honeycomb lung alone. TRIAL REGISTRATION: This study was registered on December 18, 2010 with UMIN-CTR Clinical Trial as UMIN000004749 to investigate the long-term influence of bosentan on cardiac function, as well as its cardioprotective efficacy and safety, in patients with pulmonary hypertension secondary to concurrent COPD and IPF, respectively.

Phase II study of carboplatin, docetaxel and bevacizumab for chemotherapy-naïve patients with advanced non-squamous non-small cell lung cancer.

PURPOSE: To evaluate a 3-drug combination of carboplatin, docetaxel and bevacizumab as a front-line chemotherapy for patients with advanced non-squamous non-small cell carcinoma (NSCLC), a single arm phase II study was conducted. METHODS: Patients with stage IIIB/IV or postoperative recurrent non-squamous NSCLC were treated with carboplatin (targeted area under the curve of 6 mg h/L), docetaxel (60 mg/m(2)), and bevacizumab (15 mg/kg) on day 1, repeated every 3 weeks for 4 to 6 cycles, followed by maintenance with bevacizumab every 3 weeks until disease progression or occurrence of predefined toxicity. The planned patient number was 40, and the primary endpoint was progression free survival (PFS) as assessed by independent reviewers. RESULTS: One patient refused the treatment after enrollment; thus, 39 patients were treated and analyzed. The 3-drug therapy was delivered for a median of 4 cycles, and 54 % of the patients proceeded to the maintenance therapy for a median of 4 cycles. The overall response rate was 74.4 % (29/39), with a 95 % confidence interval (CI) of 60.0 to 88.7 %. The median PFS and overall survival (OS) were 6.2 months (95 % CI, 4.8-8.5 months) and 22.4 months (95 % CI, 11.3-26.2 months), respectively. Toxicities of grade 3 or higher included neutropenia in 71.8 %, febrile neutropenia in 23.1 %, and hypertension in 38.5 % of the patients, but they were transient and manageable. CONCLUSION: The primary endpoint was met. The regimen yielded promising results with an excellent overall response rate, PFS, and OS for chemotherapy-naïve patients with advanced non-squamous NSCLC. Further studies are warranted.

Effect of Adding Inhaled Corticosteroid to Long-Acting Muscarinic Antagonist/Long-Acting Beta-Agonist Therapy Among Patients With Chronic Obstructive Pulmonary Disease.

Background The role of inhaled corticosteroid (ICS) in chronic obstructive pulmonary disease (COPD) is unclear. Hence, this study aimed to evaluate the efficacy of ICS as an add-on to long-acting muscarinic antagonist (LAMA)/long-acting beta 2 agonist (LABA), which was assessed using the impulse oscillation system (IOS), in patients with COPD. Methodology We included patients with COPD whose treatment was changed from LAMA/LABA (≥four weeks) to ICS/LAMA/LABA between April 2019 and March 2021. To gain insight into the effect and safety of ICS-containing triple therapy for COPD, pulmonary function; Short-Form 36, St. George's Respiratory Questionnaire, COPD Assessment Test, and modified Medical Research Council scores; and airway resistance assessed using the IOS from one week before LAMA/LABA was switched to ICS/LAMA/LABA therapy until more than eight but less than twelve weeks after switching were evaluated. Results In total, 46 patients with COPD (mean age: 72.28 ± 7.81 years) were included in the study. None of the pulmonary function test parameters significantly changed from baseline values (mean difference in forced expiratory volume in one second [FEV1.0]: +0.032, P = 0.12; percentage FEV1.0 [FEV1.0%]/forced vital capacity [FVC]: -0.58, P = 0.42; and FVC: +0.087, P = 0.058). Meanwhile, the IOS showed that resonant frequency (mean difference from baseline: -2.12, P < 0.0001) and bodily pain scores in the St. George's Respiratory Questionnaire (mean difference: -7.03, P = 0.031) significantly decreased. Conclusions Switching from LAMA/LABA to ICS/LAMA/LABA therapy reduces airway elasticity-to-inertial resistance ratios, which may lead to structural airway improvements in patients with COPD.

Bevacizumab plus chemotherapy in nonsquamous non-small cell lung cancer patients with malignant pleural effusion uncontrolled by tube drainage or pleurodesis: A phase II study North East Japan Study group trial NEJ013B.

BACKGROUND: Pleurodesis is the standard of care for non-small cell lung cancer (NSCLC) patients with symptomatic malignant pleural effusion (MPE). However, there is no standard management for MPE uncontrolled by pleurodesis. Most patients with unsuccessful MPE control are unable to receive effective chemotherapy. Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of MPE. This multicenter, phase II study investigated the effects of bevacizumab plus chemotherapy in nonsquamous NSCLC patients with unsuccessful management of MPE. METHODS: Nonsquamous NSCLC patients with MPE following unsuccessful tube drainage or pleurodesis received bevacizumab (15 mg/kg) plus chemotherapy every three weeks. The primary endpoint was pleural effusion control rate (PECR), defined as the percentage of patients without reaccumulation of MPE at eight weeks. Secondary endpoints included pleural progression-free survival (PPFS), safety, and quality of life (QoL). RESULTS: A total of 20 patients (median age: 69 years; 14 males; 20 adenocarcinomas; six epidermal growth factor receptor mutations) were enrolled in nine centers. The PECR was 80% and the primary end point was met. The PPFS and the overall survival (OS) were 16.6 months and 19.6 months, respectively. Patients with high levels of VEGF in the MPE had shorter PPFS (P = 0.010) and OS (P = 0.002). Toxicities of grade ≥ 3 included neutropenia (50%), thrombocytopenia (10%), proteinuria (10%), and hypertension (2%). The cognitive QoL score improved after treatment. CONCLUSIONS: Bevacizumab plus chemotherapy is highly effective with acceptable toxicities in nonsquamous NSCLC patients with uncontrolled MPE, and should be considered as a standard therapy in this setting. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Bevacizumab plus chemotherapy is highly effective with acceptable toxicities in nonsquamous NSCLC patients with uncontrolled MPE. WHAT THIS STUDY ADDS: Bevacizumab plus chemotherapy should be considered as a standard treatment option for patients with uncontrolled MPE. CLINICAL TRIAL REGISTRATION: UMIN000006868 was a phase II study of efficacy of bevacizumab plus chemotherapy for the management of malignant pleural effusion (MPE) in nonsquamous non-small cell lung cancer patients with MPE unsuccessfully controlled by tube drainage or pleurodesis (North East Japan Study Group Trial NEJ-013B) (http://umin.sc.jp/ctr/).

ProGRP as early predictive marker of non-small-cell lung cancer to small-cell lung cancer transformation after EGFR-TKI treatment.

We report a case of non-small-cell lung cancer (NSCLC) to small-cell lung cancer (SCLC) transformation after epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment. The patient was a man who diagnosed with EGFR-mutant advanced NSCLC. After he was introduced afatinib, his tumor had been reduced by the treatment. However, plasma pro-gastrin-releasing peptide (ProGRP) became higher with disease progression, and SCLC was detected at the second biopsy. It is suggested that elevation of plasma ProGRP level before EGFR-TKI therapy is useful for predicting EGFR-mutant NSCLC to SCLC transformation.

A case of nivolumab-induced isolated adrenocorticotropic hormone (ACTH) deficiency.

One of the novel PD-1 antibodies/immune checkpoint inhibitors, nivolumab is reported to be associated with a wide range of immune-related adverse events (irAEs). We hereby report a case of isolated adrenocorticotropic hormone (ACTH) deficiency developing in a patient with squamous cell lung cancer (SCC) during nivolumab therapy. CASE: A 79-year-old man with SCC was started on nivolumab therapy as a fifth-line treatment after 4 lines of cytotoxic anticancer therapy. After 20 courses of nivolumab therapy, he had nausea, appetite loss, and difficulty walking. A close laboratory examination led to the diagnosis of isolated ACTH deficiency in this patient. Hydrocortisone replacement therapy led to amelioration of his symptoms and allowed him to continue with nivolumab therapy. The present case of isolated ACTH deficiency was characterized by a slowly progressive decline in the serum sodium level, which became manifest well before appearance of any clinical symptoms, suggesting that the serum sodium level may be used to predict progression to isolated ACTH deficiency.Thus, not only serum sodium levels need to be monitored in patients suspected of having isolated ACTH deficiency, but ACTH and cortisol levels need to be monitored in those exhibiting a decline in serum sodium levels. Again, nivolumab-induced isolated ACTH deficiency needs to be appropriately diagnosed and treated to ensure that patients continue with, and maximize survival benefit from, nivolumab therapy.

Lung cancer screening--comparison of computed tomography and X-ray.

Recent studies on lung cancer screening with CT disclosed a discrepancy between its efficiency in detecting early lung cancer and a lack of proof for decreasing mortality from lung cancer. The present study, in a city in Japan where an X-ray screening program is provided, bi-annual CT screening was performed for X-ray screening negative subjects for 4 years. Ten patients with lung cancer were detected among 22,720 person-year subjects (0.044%) through the X-ray screening. Among the X-ray screening-negative subjects, 3305 subjects participated in a CT screening program resulting in the detection of 15 patients with lung cancer (0.454%). All 15 cases detected by CT screening and 5 of the 10 cases detected by X-ray screening were at stage IA. In respect of gender, histological type and CT findings, patients detected by CT screening had a better prognostic profile than those detected by X-ray screening. Survival was significantly better in the former than the latter, both in its entirety comparison and in a comparison limited to patients who underwent surgery. In conclusion, CT screening might have the potential to detect lung cancer with good prognostic factors not limited to early detection. Sufficiently long follow-up time, therefore, would be required to evaluate the efficacy for decreasing lung cancer mortality with CT screening.

Arterial blood lactate is a useful guide to when rehabilitation should be instigated in COPD.

BACKGROUND AND OBJECTIVE: Systemic effects of COPD include skeletal muscle dysfunction; the lactate threshold (LT) is an index of such dysfunction. However, it is not feasible in daily clinical practice to accurately determine the LT in all patients with COPD. There is no simple, practical and non-invasive index for determining the time at which rehabilitation should start. Previous studies have shown that the LT corresponds to the point at which the blood lactate concentration is 0.5 mmol/L above baseline (LTDelta0.5 mmol/L). The aim of the study was to assess the value of LTDelta0.5 mmol/L as an index of selecting candidates for pulmonary rehabilitation in COPD patients. METHODS: Eighteen male outpatients with COPD were enrolled. Exercise tolerance based on the 12-min walk test and treadmill exercise test, lactate concentrations and activities of daily living before and after individual exercise stress testing were assessed. RESULTS: There were no significant differences in the 12-min walk distance or metabolic equivalents between patients with and without a 0.5 mmol/L or more increase in lactate from baseline to post-walk test. However, significant differences were observed in activities of daily living, as assessed using Fletcher's scale, between those with and without a 0.5 mmol/L or greater increase in lactate from baseline to post-walk test. CONCLUSIONS: In daily clinical practice, a 0.5 mmol/L or greater increase in lactate from baseline to post-12-min walk test may be utilized as an index to determine when COPD patients should start rehabilitation, or to assess muscle alterations in the lower extremities in COPD patients undergoing rehabilitation.

Phase I study of paclitaxel, carboplatin and UFT in chemo-naive patients with advanced non-small cell lung cancer (NSCLC).

OBJECTIVE: We conducted a phase I study of paclitaxel (PTX), carboplatin (CBDCA), and UFT in chemo-naive patients with advanced non-small cell lung cancer (NSCLC). METHOD: Twenty-one chemo-naive patients with advanced NSCLC were enrolled. The study was conducted as a phase I dose-escalation study of various doses of systemic PTX followed by CBDCA on day 1 and oral UFT (400 mg/m2) on days 1-5 and 8-12, with the cycle repeated at 21-day intervals. At least three patients were enrolled in each step. RESULTS: The main toxicities were neutropenia and paresthesia, but were tolerable and reversible in all cases. Overall response rate was 57% (12 out of 21). The MTD was not reached at the highest dose level after the first cycle. Given previous recommends of PTX at 225 mg/m2 and CBDCA AUC 6 for two-drug therapy, the recommended dose for the phase II study under our regimen was set at PTX 225 mg/m2 on day 1, CBDCA AUC 6 on day 1, and UFT 400 mg/m2 on days 1-5 and 8-12. CONCLUSION: The combination of PTX, CBDCA, and UFT showed promising activity and acceptable toxicity in these chemo-naive patients, supporting the development of this combination as a feasible chemotherapeutic option for advanced NSCLC.

A case of anti-aminoacyl tRNA synthetase (ARS) antibody-positive polymyositis (PM)/dermatomyositis (DM)-associated interstitial pneumonia (IP) successfully controlled with bosentan therapy.

A 72-year-old woman was admitted to our hospital and was diagnosed with interstitial pneumonia (IP) associated with amyopathic dermatomyositis (ADM). The patient experienced three acute IP exacerbations in the 7 years that followed, which were each treated and resolved with steroid pulse therapy. The patient was closely examined for respiratory failure with right heart catheterization (RHC), which demonstrated that she had a mean pulmonary artery pressure (mPAP) of 34 mmHg. The patient was thus diagnosed as having pulmonary hypertension (PH) associated with anti-synthetase syndrome (ASS) and was started on bosentan therapy, which led to improvements in mPAP as well as in subjective symptoms over time. Indeed, she had had no acute exacerbations with serum markers of IP remaining low over 6 years following initiation of bosentan therapy, suggesting that bosentan may have a role in controlling IP. In addition, she was confirmed to be anti-ARS antibody-positive after 5 years of bosentan therapy, when anti-aminoacyl tRNA synthetase (anti-ARS) antibody testing became available.

Localized pulmonary crystal-storing histiocytosis complicating pulmonary mucosa-associated lymphoid tissue lymphoma presenting with multiple mass lesions.

Crystal-storing histiocytosis (CSH) is an uncommon finding in lymphoplasmacytic disorders that presents histiocytes with abnormal intralysosomal accumulations of immunoglobulin light chains as crystals of unknown etiology. A 38-year-old woman with antiphospholipid syndrome had a surgical lung biopsy because of multiple lung mass lesions. In a right middle lobe lesion, lymphoplasmacytic cells had a monocytoid appearance, destructive lymphoepithelial lesions, and positive immunoglobulin heavy chain (IGH) gene rearrangements. A right upper lobe lesion manifested proliferating rounded histiocytes with abundant, deeply eosinophilic cytoplasm and negative IGH gene rearrangements. Electron microscopy and mass spectrometry revealed a case of pulmonary CSH: abnormal proliferation of the immunoglobulin κ chain of a variable region that may be crystallized within plasma cells and histiocytes. We report a rare case of localized pulmonary CSH complicating pulmonary mucosa-associated lymphoid tissue lymphoma with multiple mass lesions. We demonstrate advances in the understanding of the pathogenesis of CSH by various analyses of these lesions.

Weekly administration of irinotecan (CPT-11) plus cisplatin for non-small cell lung cancer.

BACKGROUND: Weekly administration of irinotecan plus cisplatin was evaluated for untreated patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Sixty mg/m(2) of irinotecan plus 30 mg/m(2) of cisplatin were administered on days 1, 8 and 15 every 4 weeks. Patients with no evidence of disease progression were treated with at least two cycles (8 weeks). Of the 39 patients, 29 were provided an antidiarrheal program consisting of sodium bicarbonate and magnesium oxide. RESULTS: There were 13 partial responses and an overall response rate of 33.3% [95% CI: 20%-50%]. The median time to progression and survival were 64 days and 12.8 months, respectively. Grade 4 neutropenia occurred in 15.4% of the patients, and Grade 3 and 4 diarrhea was observed in 12.8% and 2.6%, respectively. The incidence of leukopenia of grade 3-4 was significantly lower in patients provided with the antidiarrheal program due to lack of decrease in the lymphocyte count. CONCLUSION: This phase II study indicated that weekly irinotecan plus cisplatin administration was a promising treatment for untreated NSCLC.

Metastatic thoracic lymph node carcinoma of unknown origin on which we performed two kinds of immunohistochemical examinations.

Metastatic cancers of the thoracic lymph nodes without primary sites are rare. Such cancers are difficult for clinicians to manage as identifying the primary sites is difficult in using routine histologic examinations alone. We searched for the site of the primary lesion using immunohistochemical exploration of cytokeratin (CK) and thyroid transcription factors 1 (TTF-1), and 2-[18F] and fluorodeoxyglucose positron emission tomography (FDG PET) in a patient with cancer of the hilar lymph node without any known primary site. To our knowledge, there are no previous similar reports. A 45-year-old man presenting with a tumor in the right hilar region, underwent surgical resection of the tumor, resulting in a diagnosis of metastatic cancer of the bronchopulmonary lymph nodes. An immunohistochemical examination revealed the neoplastic lesion to be positive for CK7, negative for CK20, and negative for TTF-1. Repeated searches to identify the site of the primary lesion by FDG PET over the 35 months since operation have failed to locate a primary site.

Efficacy of triple antiemetic therapy (palonosetron, dexamethasone, aprepitant) for chemotherapy-induced nausea and vomiting in patients receiving carboplatin-based, moderately emetogenic chemotherapy.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is a major adverse toxicity of cancer chemotherapy. Recommended treatments for prevention of CINV vary among published guidelines, and optimal care for CINV caused by moderately emetogenic chemotherapy has not been established. This study assessed the efficacy and safety of triple antiemetic therapy comprising palonosetron, dexamethasone and aprepitant for carboplatin-based chemotherapy. Chemotherapy-naïve patients with lung cancer scheduled for a first course of a carboplatin-containing regimen formed the study cohort. Patients were pretreated with antiemetic therapy comprising palonosetron (0.75 mg, i.v.) and dexamethasone (9.9 mg, i.v.) on day 1, and aprepitant (125 mg, p.o.) on day 1 followed by 80 mg on days 2 and 3. Primary endpoint was the proportion of patients who did not experience vomiting and did not require rescue medication [complete response (CR)] in the acute phase (0-24 h), late phase (24-168 h) and overall. Secondary endpoint was the proportion of patients who experienced no vomiting episodes and no more than mild nausea without the need for rescue medication [complete control (CC)]. RESULTS: Prevalence of a CR during the acute phase, delayed phase, and overall was 100, 91.9 and 91.9%, whereas that of CC was 100, 84.4 and 84.4%, respectively. The most common adverse event was mild constipation; severe adverse events related to antiemetic treatment were not observed. CONCLUSION: Triple antiemetic therapy comprising palonosetron, dexamethasone and aprepitant shows excellent effects in the prevention of CINV in patients receiving a carboplatin-containing regimen.

Bosentan for pulmonary hypertension secondary to idiopathic pulmonary fibrosis.

Pulmonary hypertension is a poor prognostic factor in patients with interstitial lung disease. No established treatment exists for pulmonary hypertension secondary to interstitial pneumonia. We describe the case of an 81-year-old woman with idiopathic pulmonary fibrosis (IPF), who was admitted to our hospital due to aggravation of dyspnea and decreased oxygen saturation, as well as onset of orthopnea and rapidly progressing edema. The transthoracic echocardiography and right heart catheterization showed the mean pulmonary artery pressure was 39 mmHg and the mean pulmonary capillary wedge pressure was 9 mmHg. After various examinations, the diagnoses of pulmonary hypertension (PH) due to IPF and of congestive heart failure secondary to PH were established. Diuretic therapy was started, but the patient's condition showed poor improvement. Subsequent initiation of oral bosentan therapy led to improvement in symptoms and findings. At the follow-up assessment one year later her pulmonary function showed no significant changes and no apparent worsening of arterial blood gases, with evident improvement of PH, WHO functional class, maximum exercise tolerance on treadmill exercise testing, right heart catheterization, and transthoracic echocardiography. This report describes a case of successful treatment with bosentan for severe pulmonary hypertension in a patient with idiopathic pulmonary fibrosis. We also present a review of the literature on treatment of pulmonary hypertension in patients with chronic lung disease. Bosentan appears to be efficacious in some patients with pulmonary hypertension secondary to idiopathic interstitial pneumonitis.

Human pulmonary dirofilariasis in a patient whose clinical condition altered during follow-up.

Pulmonary dirofilariasis is a rare disease. We have experienced a case which developed pleural effusion while being followed, rendering it difficult to establish the diagnosis. The patient, a 53-year-old woman, had previously undergone two operations; one for uterine cancer and another for breast cancer. She developed a cough in February 2002, and chest computed tomography (CT) scans disclosed a nodular mass in the right lung. A biopsy revealed a fibrous nodule with macrophage aggregation. Pleural effusion was demonstrated on chest CT scans performed in May. As the possibility of malignant tumor could not be ruled out, an operation was undertaken. The nodular lesion showed marked coagulation necrosis, and dead parasites were noted in the vascular lumen. The parasites had the characteristic morphological features of Dirofilaria immitis. Immunological studies produced a positive test result for the anti-dirofilaria immitis antibody; hence a diagnosis of pulmonary dirofilariasis was made.

[The frequency profiles of size of two-step tuberculin skin tests with histories of BCG vaccinations and tuberculin tests among hospital employees].

In 1998, Prevention Committee of the Japanese Society for Tuberculosis announced guidelines for dealing with nosocomial tuberculosis infections. These guidelines recommended the two-step tuberculin tests (TST) as baseline data for each medical employee when they started to work. If accurate records of previous TSTs are available in addition to baseline data, they are useful to evaluate the presence of tuberculosis infection when they started to work. We therefore studied the frequency profile of size of TST among medical employees in INBA-HITEC Medical Center and discussed methods to improve investigative measures for tuberculosis infection, and prior to skin testing we asked self-reporting questionnaires regarding history of previous BCG vaccinations and TSTs. We expected that their records of previous TSTs were accurately preserved, however, records of previous TSTs reported by medical employees were found to be inaccurate. From two-step TSTs results, the magnitude of booster phenomenon was defined by diameter of erythema and induration. Results demonstrated that the increase of induration size was larger in subjects > or = 41-years-old than in subjects < 41-years-old. Regarding booster phenomenon, no statistically significant differences were detected according to type of duty post. Many subjects with size of TST erythema > or = 30 mm on the first test showed increase erythema > or = 10 mm on the second test. We therefore suggest that the second test be made for those showing reaction size > or = 30 mm on the first test.

Assessment of the relationship between right ventricular function and the severity of obstructive sleep-disordered breathing.

INTRODUCTION: Some complications of obstructive sleep-disordered breathing (OSDB), such as heart failure including right ventricular (RV) overload, are more serious than an increase of the apnea-hypopnea index (AHI) or respiratory disturbance index (RDI). These serious complications may contribute to the worsening of OSDB. OBJECTIVE: To explore the relationship between RV function in OSDB patients while awake and the severity of OSDB. METHODS: Fifty-eight patients were evaluated to determine the cause of OSDB and were subjected to various examinations, including cardiac ultrasonography. Of them, 54 were included in this analysis. RESULTS: Isovolumetric relaxation time decreased as AHI increased to about 40 events/h and increased when AHI increased beyond 40 events/h. The total ejection isovolume index increased as AHI increased to approximately 35 events/h and decreased when AHI increased beyond 35 events/h. CONCLUSIONS: RV function gradually deteriorated from the early stages of obstructive sleep apnea syndrome, even though there was no apparent increase in pulmonary artery pressure. The results of this study indicated that the progression of OSDB correlated with RV function determined in patients while awake. Further studies are required to clarify this relationship, including assessment of components of RV function.