Osamu Nishiyama

Pulmonary Hypertension as a Prognostic Indicator at the Initial Evaluation in Idiopathic Pulmonary Fibrosis

Background: The impact of pulmonary hypertension (PH) on survival has been demonstrated in severe cases with idiopathic pulmonary fibrosis (IPF) who were referred for transplantation. However, whether PH is a predictor of survival remains unclear in milder cases. Objectives: To evaluate the survival impact of pulmonary artery pressure measured during the initial evaluation in patients with IPF. Methods: We retrospectively analyzed the initial evaluation data of 101 consecutive IPF patients undergoing right heart catheterization. Patients evaluated with supplemental oxygen were excluded. Predictors of 5-year survival were analyzed using the Cox proportional model. Results: The mean forced vital capacity (FVC) % predicted, diffusing capacity of the lung for carbon monoxide (DLCO) % predicted, and mean pulmonary artery pressure (MPAP) were 70.2 ± 20.1%, 47.9 ± 19.5%, and 19.2 ± 6.5 mm Hg, respectively. A univariate Cox proportional hazard model showed that the body mass index, %FVC, %DLCO, baseline PaO2, modified Medical Research Council score, 6-min walk distance, and lowest SpO2 of the 6-min walk test were significantly predictive of survival. The MPAP and pulmonary vascular resistance of right heart catheterization were also significant. With stepwise, multivariate Cox proportional analysis, MPAP (HR = 1.064; 95% CI 1.015-1.116, p = 0.010) and %FVC (HR = 0.965, 95% CI 0.949-0.982, p < 0.001) were independent determinants of survival. Analysis of the receiver operating curve revealed MPAP >20 mm Hg to be optimal for predicting the prognosis. Conclusions: Higher MPAP and lower %FVC at the initial evaluation were significant independent prognostic factors of IPF. The current results suggested the importance of the initial evaluation of PH for patients with IPF.

Serum KL-6 in fibrotic NSIP: Correlations with physiologic and radiologic parameters

BACKGROUNDS Fibrotic nonspecific interstitial pneumonia (f-NSIP) has been recognized as a distinct disease entity. KL-6 has been reported to be a useful serum marker in interstitial lung diseases. However, few previous reports evaluated the value of serum KL-6 exclusively in f-NSIP, as distinct from other subtypes of idiopathic interstitial pneumonia, therefore the associations of serum KL-6 with clinical and radiologic findings in this population remain unclear. METHODS Serum KL-6 levels were measured in twenty-six consecutive patients with f-NSIP diagnosed by surgical lung biopsy. Pulmonary function testing, bronchoalveolar lavage, subjective measurement of dyspnea using baseline dyspnea index (BDI), and HRCT were performed in parallel. Two radiologists conducted independent visual examinations of the pattern and extent of abnormalities on HRCT. RESULTS Serum KL-6 levels were elevated above the cut-off level in all patients. In univariate analysis serum KL-6 levels showed negative correlations with BDI (rho=-0.52; p<0.01). Serum KL-6 had positive correlations with the extent of several patterns of opacities (rho=0.56-0.62; p<0.01). Among them, only the extent of traction bronchiectasis in HRCT showed significant association with serum KL-6 in multivariate analysis (beta-coefficient=0.043; p<0.01). CONCLUSIONS Serum levels of KL-6 were elevated in f-NSIP, and were correlated with the extent of fibrotic abnormalities on HRCT, suggesting a value of serum KL-6 as a marker for fibrosis in f-NSIP.

Reperfusion through balloon catheter to minimize myocardial infarction during the interval between failed percutaneous transluminal coronary angioplasty and emergency coronary artery bypass grafting

SummaryA 65-year-old man was admitted with chest pain. A diagnosis of spastic angina was made because of symptoms of recurrent anginal attacks associated with ST-segment elevations in the electrocardiogram. A selective coronary arteriogram revealed a 90% diameter narrowing of the proximal left anterior descending coronary artery (LAD). No angiographically visible collaterals from the right coronary artery to the LAD were observed. The ventriculogram showed normal contraction of the left ventricle with an ejection fraction of 65%. Percutaneous transluminal coronary angioplasty (PTCA) failed resulting in total occlusion of the stenosis. Repeat PTCA at a higher pressure and of longer duration failed to redilate the artery. Reperfusion with the blood from the femoral artery through the balloon catheter, which was used for the PTCA, was carried out until coronary artery bypass grafting (CABG). Blood flow rate of perfusion was approximately 25 ml/min. Reperfusion through the balloon catheter reduced chest pain and ST-segment elevations in the electrocardiogram. The patient tolerated the operative procedure well and his post-operative course was uncomplicated. The interval between the acute occlusion and revascularization by CABG was approximately 4 1/4 h. The ventriculogram taken 56 days after the CABG demonstrated normal contraction of the anterior wall of the left ventricle with an ejection fraction of 63%. Abnormal Q waves did not appear in precordial leads of the electrocardiogram after the surgery. The thallium scintigram showed no perfusion defects.In conclusion, this case suggested that autologous blood reperfusion through balloon cathether would be worth attempting in some cases for minimization of myocardial infarction during the interval between failed PTCA and emergency CABG.

Efficacy of combined therapy with cyclosporin and low-dose prednisolone in interstitial pneumonia associated with connective tissue disease.

Background: The optimal treatment method for interstitial pneumonia (IP) with connective tissue disease (CTD) remains controversial. In addition, a clinically meaningful end point to judge drug efficacy has not been fully investigated. Objectives: The aim of this study was to evaluate, from various aspects, the therapeutic benefit and tolerability of combined therapy with cyclosporin A (CsA) and low-dose prednisolone (PSL) for chronic fibrosing CTD-IP patients. Methods: A total of 26 CTD-IP patients diagnosed by surgical lung biopsy and subsequently treated with the above combination therapy were retrospectively reviewed. The therapeutic regimen comprised methylprednisolone induction therapy for 2-4 weeks, followed by a combined therapy of CsA with low-dose PSL for 1 year. Evaluation of the therapeutic benefit was based on not only pulmonary function but also exercise capacity, health-related quality of life and dyspnea. Results: After 1 year of therapy, clinically significant improvements in forced vital capacity (≥10%), carbon monoxide diffusing capacity of the lung (≥15%), 6-min walk distance (≥28 m), and St. Georges Respiratory Questionnaire (≤-7) were observed in 61.5, 69.2, 61.5 and 69.2% of the patients, respectively. All measurements showed statistically significant improvements compared with baseline values. The 1-year treatment did not need to be discontinued in any patients due to unacceptable toxicity, and no deaths occurred. Conclusions: Combined therapy with CsA and low-dose PSL for CTD-IP patients was well-tolerated and patients displayed a noteworthy response.

Prognosis in Patients with Non-Small Cell Lung Cancer Who Received Erlotinib Treatment and Subsequent Dose Reduction due to Skin Rash

Background: Severe skin rash as toxicity of erlotinib has been reported in relation to better response and survival. However, some patients require dose reduction due to skin toxicities, and their prognosis remains uncertain. We retrospectively evaluated the clinical course of non-small cell lung cancer patients receiving erlotinib at a reduced dose because of skin rash. Patients and Methods: Among 76 patients treated with erlotinib, 55 patients who developed skin rash severer than grade 2 were divided into 2 groups: 24 patients treated with erlotinib with dose reduction because of skin rash (dose reduction group) and 31 patients without any dose reduction (non-dose reduction group). Results: The median progression-free survival in the dose reduction and non-dose reduction groups was 341 and 70 days, respectively, and the median overall survival was 566 and 202 days, respectively (p < 0.001). In the dose reduction group, no smoking history, female sex, epidermal growth factor receptor gene mutation, and grade 3 skin rash were significant baseline factors. Conclusions: Patients who received erlotinib at a reduced dose following skin rash showed better survival than those without reduction. In cases of intolerable skin rash, patients may benefit from continuous treatment with a reduced dose of erlotinib.

The incidence of discrepant regional myocardial uptake between 201 thallium and 123 I-BMIPP SPECT in patients with coronary heart disease

Myocardial perfusion and fatty acid uptake at rest were assessed by SPECT with 201Tl (Tl) and 123I-BMIPP (BMIPP) in 50 consecutive patients with coronary heart disease. Discrepant regional myocardial uptake was observed in 19 patients and classified into the following two groups: mismatch (MM; Tl uptake > BMIPP uptake, n = 14, mean age, 66 years) and paradoxical mismatch (PM; Tl uptake < BMIPP uptake, n = 5, mean age, 68 years). In the MM group, 77% was single- or zero-vessel disease and the artery-perfused region in the mismatched area was almost always ischemia related. Sixty percent of the regions observed with the PM were related to the inferior wall. In the PM group, 80% of cases were associated with multivessel stenoses and 60% of cases was suffered from ischemic attack within a week before scintigraphy. In conclusion, mismatch was related to abnormal fatty acid uptake caused by coronary heart disease. Although the paradoxical mismatch might mainly be related to diaphragmatic attenuation of Tl scans and augmented artifacts of BMIPP scans in the inferior wall, we should not overlook severe coronary heart disease in patients with paradoxical mismatched phenomenon.

The COPD assessment test and St George's Respiratory Questionnaire: are they equivalent in subjects with COPD?

Background The chronic obstructive pulmonary disease (COPD) assessment test (CAT) is a short questionnaire that has facilitated health status measurements in subjects with COPD. However, it remains controversial as to whether the CAT can be used as a suitable substitute for the St George’s Respiratory Questionnaire (SGRQ). This study investigated the reliability and score distributions of the CAT and SGRQ and evaluated which factors contributed to health status for each questionnaire. Methods A total of 109 consecutive subjects with stable COPD from a single center were enrolled in this study. Each subject completed pulmonary function tests, exercise tests, and the following self-administered questionnaires: the Baseline Dyspnea Index, the Hospital Anxiety and Depression Scale, the CAT, and SGRQ. Results Internal consistencies of CAT and SGRQ total scores were both excellent (Cronbach’s α coefficients =0.890 and 0.933). Statistically significant correlations were observed between CAT and SGRQ total scores (R=0.668, P<0.001). Correlations of CAT scores with parameters related to pulmonary function, dyspnea, exercise performance, and psychological factors were inferior to correlations with those parameters with SGRQ total scores. Both multiple regression analyses and principal component analyses revealed that there were slight differences between SGRQ total scores and CAT scores. Conclusion The CAT is similar to SGRQ in terms of discriminating health status. However, we demonstrated that what is assessed by the CAT may differ slightly from what is measured by SGRQ.

Paradoxical regional myocardial uptake between 201Thallium and 123I-BMIPP SPECT in patients with cardiomyopathy.

Abstract. The clinical significance of the paradoxical mismatched phenomenon between 201Tl and 123I-BMIPP is still unknown. We report two cases that revealed paradoxical regional myocardial uptake between two tracers in patients with cardiomyopathy. There may be abnormal myocardium in these patients where active transportation of 201Tl is disturbed and passive transportation of 123I-BMIPP is not disordered.

Clinical spectrum and prognostic factors of possible UIP pattern on high-resolution CT in patients who underwent surgical lung biopsy

Background Few studies have reported the diagnostic variability in patients with a possible usual interstitial pneumonia (UIP) pattern on high-resolution CT (HRCT) who underwent surgical lung biopsy (SLB), and the prognostic factors for these patients have not been fully evaluated. We retrospectively investigated the frequency of idiopathic pulmonary fibrosis (IPF) and prognostic factors in patients with possible UIP pattern on HRCT. Methods Consecutive patients who had a possible UIP pattern on HRCT, underwent SLB, and had a diagnosis of IIPs before SLB were retrospectively recruited from 10 hospitals. Diagnoses were made based on multidisciplinary discussion using the criteria for current IPF guidelines and multidisciplinary classification for IIPs in each hospital. Results 179 patients who underwent SLB were enrolled. The diagnoses were IPF in 91 patients (51%), unclassifiable IIPs in 47 (26%), idiopathic NSIP in 18 (10%), and chronic hypersensitivity pneumonia in 17 (9%). One-year FVC changes showed significant differences between IPF and non-IPF (-138.6 mL versus 18.2 mL, p = 0.014). Patients with IPF had a worse mortality than those with non-IPF (Logrank test, p = 0.025). Multivariable Cox regression analysis demonstrated that diagnoses of IPF (HR, 2.961; 95% CI, 1.183–7.410; p = 0.02), high modified MRC score (HR, 1.587; 95% CI, 1.003–2.510; p = 0.049), and low %FVC (HR, 0.972; 95% CI, 0.953–0.992; p = 0.005). Conclusions About a half of patients with a possible UIP pattern on HRCT had diagnoses other than IPF, and patients with IPF had a worse mortality than those with an alternative diagnosis. We reaffirmed that multidisciplinary discussion is crucial in patients with possible UIP pattern on HRCT.

Joint Annual Meeting of the Swiss Society for Allergology and Immunology and the Swiss Respiratory Society, Bern, April 17-19, 2013

Introduction Bioaerosols such as grain dust (GD) elicit direct immunological reactions within the human respiratory system. Workplace-dependent exposure to GD may induce asthma, chronic bronchitis, and hypersensitivity pneumonitis. Aims To assess the clinical impact of occupational exposure to GD and to determine quantitative biological markers of bioaerosol exposure in grain workers. Methods This longitudinal study has been conducted from summer 2012 to summer 2013, comprising 6 groups of 30 active workers with different GD exposure patterns (4 groups of grain workers, 2 control groups). Two evaluations at high- and low-exposing seasons take place, during which an occupational and a medical history are questionnaire-assessed, lung function is evaluated by spirometry, airway inflammation is measured by exhaled nitric oxide (eNO) and specific blood IgG and IgE are titrated. Results The preliminary results are those of 2 of the 4 exposed groups, (harvesters and mill workers), compared to the control groups, at first assessment (n=100). Mean age is 38.4 [years]; 98% are male. Exposed groups differ from controls (p Conclusion Preliminary results show a higher prevalence of clinical symptoms and a lower mean PEF value in the groups exposed to GD.