Oscillometry as a Predictor of Exercise Tolerance in COPD.

The usefulness of the oscillometry, known as forced oscillation technique, for predicting exercise tolerance in subjects with COPD is unknown. To test the hypothesis, we investigated whether oscillometry could predict a 6-minute walking distance (6MWD) <350 m in the 6-minute walk test (6MWT).This was a prospective, observational study. Fifty-seven subjects with COPD who attended outpatient clinics for routine checkups at Shizuoka General Hospital between April 2015 and April 2016 (54 males; median age, 70 years; and %FEV1, 61.0%). Modified MRC dyspnea scale (mMRC), COPD Assessment Test (CAT), oscillometry, spirometry, and 6MWT were performed in a stable condition. The participants were classified into subjects with 6MWD ≥350 m or 6MWD <350 m, and the predictor of 6MWD <350 m was assessed.Of the 57 total subjects, 43 (75.4%) had a 6MWD ≥350 m, and 14 (24.6%) had a 6MWD <350 m. Between the two groups, there were significant differences in mMRC scale, GOLD stages, CAT scores, FEV1, IC, 6MWD, lowest SpO2, maximum Borg scale, respiratory resistance (Rrs), and reactance (Xrs). In multivariate regression analysis, a 6MWD <350 m was independently predicted by CAT scores (OR 1.15, 95% CI: 1.01-1.30) and inspiratory R5 (OR 6.01, 95% CI: 1.09-33.30). In receiver operating characteristic curves, the area under the curve was 0.76, 0.78, and 0.85 for CAT scores, R5, and CAT scores + R5, respectively, with the best cutoff value of 17 and 2.82 cmH20/L/s. In conclusion, the oscillatory parameter, inspiratory R5, predicted low exercise tolerance in COPD subjects.

A case of acute respiratory distress syndrome due to lymphography with Lipiodol for chylothorax after esophagectomy.

BACKGROUND: Lymphography with Lipiodol is useful for chylothorax. There were many slight complications, but reports of acute respiratory distress syndrome (ARDS) after lymphography were few. CASE PRESENTATION: A 75-year-old man with esophageal cancer developed chylothorax after esophagectomy. Conservative treatment was ineffective, and he underwent lymphography with 8.5 mL of Lipiodol. He developed a high fever soon after lymphography, followed by severe ARDS requiring artificial respiration 5 days later. He recovered from ARDS but subsequently developed pulmonary fibrosis and was discharged with domiciliary oxygen therapy 3 months later. CONCLUSION: Although ARDS is a rare complication of lymphography with Lipiodol, this procedure should be applied carefully in patients with chylothorax.

Forced oscillation technique as a predictor of FEV1 improvement in asthma.

The usefulness of the forced oscillation technique (FOT) for predicting the treatment outcomes in untreated asthmatic patients is unknown. We investigated whether FOT could predict an improvement in FEV1 following treatment. FOT, spirometry, and fractional exhaled nitric oxide were performed in 31 outpatients before and after undergoing a minimum of two months combination therapy of inhaled corticosteroids and long-acting ß2-agonists. The patients were classified as responders or nonresponders to treatment based on the presence or absence of a 10% improvement in the FEV1. The responders to the treatment regimen exhibited lower FEV1, FEV1/FVC, FEF25-75%, and higher respiratory resistance at 5Hz (R5), as well as a difference between R5 and R20 (R5-R20) at baseline compared to the nonresponders. In the multivariate logistic regression analyses, a change in FEV1 greater than 10% was independently predicted by the R5 (adjusted odds ratio: 15.9). The ROC curve analyses revealed that the area under the curve for R5 (0.731) was larger than that of the other parameters. Thus, R5 is a forced oscillatory parameter and predicts an improvement in FEV1 following treatment.

Association of the forced oscillation technique with negative expiratory pressure in COPD.

Expiratory flow limitation (EFL) during tidal breathing is common in patients with severe COPD, and a major determinant of dynamic hyperinflation and exercise limitation. The negative expiratory pressure (NEP) technique has been the gold standard to detect EFL, while the forced oscillation technique (FOT) has also been reported to detect it. However, the association of FOT with NEP is not fully understood. We assessed whether broadband frequency FOT would predict the presence of EFL measured by NEP. FOT, NEP, and spirometry were performed in 51 patients with COPD. The extent of emphysema was measured by high-resolution computed tomography and scored. Fifteen patients were classified into the EFL-positive group and 36 into the EFL-negative group. In multivariate logistic regression analysis, EFL was independently predicted by emphysema score, forced vital capacity, and whole-breath respiratory system reactance at 5Hz (X5). The receiver operator characteristic curve analysis revealed that inspiratory X5 best predicted EFL-positivity. X5-related forced oscillatory parameters are useful for detecting EFL in the management of COPD.

Real-world effect of gastroesophageal reflux disease on cough-related quality of life and disease status in asthma and COPD.

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most common causes of chronic cough and often coexists with asthma or chronic obstructive pulmonary disease (COPD); however, it is unknown whether there are differences in the effect of GERD on these diseases. The purpose of this study was to assess the difference in the effect of GERD on cough-related quality of life and disease status in asthma and COPD in a real-world setting. METHODS: Subjects were 132 patients with overall controlled asthma and 102 patients with stable COPD. They completed the frequency scale for symptoms of GERD (FSSG), a validated Japanese questionnaire for GERD, the Leicester Cough Questionnaire (LCQ), and the Asthma Control Test (ACT) or COPD assessment test (CAT) questionnaires. RESULTS: We found that 29 (22.0%) patients with asthma and 22 (21.6%) patients with COPD had GERD. There was no difference in the FSSG scale between the diseases. The patients with GERD, regardless of having asthma or COPD, had lower LCQ scores affecting all health domains and lower ACT or higher CAT scores than those without GERD. Overall, the patients with COPD had lower LCQ scores regardless of the presence or absence of GERD. The FSSG scale was negatively correlated with the LCQ total score in asthma and in COPD. In contrast, the FSSG scale was positively correlated with the CAT score but not with the ACT score. CONCLUSIONS: Patients with GERD had impaired cough-related quality of life, poor asthma control or more symptoms and impacts of COPD.

Inspiratory resonant frequency of forced oscillation technique as a predictor of the composite physiologic index in interstitial lung disease.

The composite physiologic index (CPI), which is derived from FEV1, FVC, and diffusing capacity, has been developed to predict the extent of fibrosis on high-resolution computed tomography (HRCT). However, the relevance to the forced oscillation technique (FOT) is not fully understood. We hypothesized that FOT would independently predict the CPI in interstitial lung disease (ILD). In this cross-sectional study we assessed the relationship between pulmonary function tests, forced oscillatory parameters, and the degree of fibrosis in ILD. Spirometry, evaluation of diffusing capacity for carbon monoxide, and the broadband frequency FOT were performed in 93 patients with a clinical/HRCT diagnosis of ILD. The CPI was calculated and fibrosis extent was measured by HRCT and scored. Univariate analyses revealed that, of the forced oscillatory parameters, inspiratory resonant frequency best correlated with FVC, FEV1, diffusing capacity, CPI, and fibrosis score. In multiple regression analyses, CPI was independently predicted by inspiratory resonant frequency and fibrosis score (model R(2)=0.405, p<0.0001).

Predictors of expiratory flow limitation measured by forced oscillation technique in COPD.

BACKGROUND: Expiratory flow limitation (EFL) during tidal breathing is common in patients with severe COPD, and a major determinant of dynamic hyperinflation and exercise limitation. EFL can be measured by the forced oscillation technique (FOT); however, the relevance to clinical parameters is not fully understood. We hypothesized that emphysema extent and pulmonary function would contribute independently to the degree of EFL. METHODS: Broadband frequency FOT and pulmonary function tests were performed in 74 patients with COPD to derive respiratory system resistance (Rrs) and reactance (Xrs), and the EFL index as expressed by the differences between inspiratory and expiratory phases of Xrs at 5 Hz (ΔX5). Emphysema extent was measured by high-resolution computed tomography and scored. RESULTS: On the basis of the median value of ΔX5 (0.55 cmH2O/L/s), patients were classified into a high or low EFL index group. In multivariate regression analyses, a high EFL index was independently predicted by emphysema score, peripheral airway obstruction (forced expiratory flow between 25% and 75% of forced vital capacity), hyperinflation (functional residual capacity), and airway caliber (whole-breath Rrs at 5 Hz). CONCLUSIONS: EFL measured by FOT is a global measure of COPD that has separable etiologies and is useful for evaluating the disease condition.

Development of allergic bronchopulmonary aspergillosis with central bronchiectasis over a 10-year period: the need to recheck allergen sensitization.

A 55-year-old woman visited our hospital for an investigation of central bronchiectasis, mucoid impaction and infiltrative shadows on chest CT. She had a 10-year history of bronchial asthma; however, her adherence to treatment was poor. Based on the presence of peripheral blood eosinophilia and immediate cutaneous reactivity to Aspergillus fumigatus, the patient was clinically diagnosed with allergic bronchopulmonary aspergillosis. Her condition and CT findings improved with systemic corticosteroid therapy. It was found that the patient had not been sensitized to Aspergillus 10 years earlier, indicating that single testing is inadequate for the early diagnosis of this disease.

Usefulness of Colored 3D Imaging of Respiratory Impedance in Asthma.

PURPOSE: Recently, the clinical application of the forced oscillation technique (FOT) has progressed with the spread of commercially available FOT devices, including the impulse oscillation system and MostGraph. We investigated the usefulness of color 3D imaging of respiratory impedance in asthma using MostGraph. METHODS: Whole-breath and within-breath respiratory system resistance (Rrs) and reactance (Xrs) were measured in 78 patients with asthma. Color 3D images were classified into three patterns: the chronic obstructive pulmonary disease (COPD)-like pattern (high values of Rrs and Xrs with a marked respiratory cycle and frequency dependence), the asthma pattern (moderately high Rrs over the entire frequency and a respiratory cycle with slight Xrs changes), and a normal-like pattern (low Rrs and Xrs with few within-breath changes). The classification was performed by three researchers, who were unaware of the clinical information, and the clinical characteristics were compared among the three groups. RESULTS: Color 3D imaging provided a COPD-like pattern in 25 patients, an asthma pattern in 39 patients, and a normal-like pattern in 14 patients. Patients with the COPD-like pattern were predominantly female with a higher body mass index, lower forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), and higher Rrs and Xrs values (whole-breath and within-breath variation). Those with the normal pattern had higher FEV1 and FVC, and a lower single-breath nitrogen washout slope. There were no differences in asthma control or exhaled nitric oxide levels among the three groups. CONCLUSIONS: These results suggest that color 3D imaging of respiratory impedance may show asthma phenotypes.

Predictors of phase III slope of nitrogen single-breath washout in COPD.

The nitrogen (N2) single-breath washout (SBW) test is a measure of ventilation distribution inhomogeneity and also a small airway function that offers complementary information to spirometry; however, the relevance to the forced oscillation technique (FOT) and pulmonary emphysema in COPD is not fully understood. We hypothesized that pulmonary functions, forced oscillatory parameters, and emphysema extent would contribute independently to the results of the SBW test. In this cross-sectional study we assessed the relationship between the phase III slope (delta N2) derived from N2 SBW and these parameters. Spirometry, lung volumes, N2 SBW, and the broadband frequency FOT were performed in 56 patients with COPD. Emphysema extent was measured by high-resolution computed tomography and scored. In multiple regression analyses, the delta N2 was independently predicted by forced vital capacity, resonant frequency, and emphysema score (R(2)=0.57, p<0.0001). The degree of ventilation inhomogeneity derived from N2 SBW is independently predicted by spirometry, lung mechanics, and the degree of emphysema.

Respiratory mechanics measured by forced oscillation technique in combined pulmonary fibrosis and emphysema.

The coexistence of emphysema and pulmonary fibrosis is known as combined pulmonary fibrosis and emphysema (CPFE). The aim of this study was to compare the lung mechanics measured by multi-frequency forced oscillation technique (FOT) among patients with CPFE, interstitial pneumonia (IP), and chronic obstructive pulmonary disease (COPD). FOT and pulmonary function tests were performed in 41 patients with CPFE, 47 with IP, and 86 with COPD. Whole-breath resistance at 20 Hz was significantly lower in patients with CPFE than in those with IP or COPD, irrespective of the severity of airflow limitation. Within-breath analyses of resistance revealed no difference among the 3 groups; however, the difference between inspiratory and expiratory phases of reactance at 5 Hz, which reflects expiratory flow limitation, in patients with CPFE was significantly higher than in those with IP and lower than in those with COPD. In conclusion, both emphysema and fibrosis affect lung mechanics in CPFE, leading to different findings from IP or COPD alone.

Colored 3-dimensional analyses of respiratory resistance and reactance in COPD and asthma.

BACKGROUND: The forced oscillation technique (FOT) is a noninvasive method with which to measure respiratory system resistance (Rrs) and reactance (Xrs) at a wide range of frequencies during breathing at rest in a short time. The purpose of this study was to assess the differences in Rrs and Xrs between patients with chronic obstructive pulmonary disease (COPD) and asthma using a new method of FOT with colored 3-dimensional visualization. METHODS: Fifty-one patients with stable COPD and 49 patients with controlled or partly controlled asthma were enrolled. Whole-breath or within-breath changes of Rrs and Xrs were measured and compared between the diseases. RESULTS: The colored 3-dimensional images clarified the complex oscillatory properties of the respiratory system. Whole-breath resistance (the difference in Rrs at 5 and 20 Hz) and reactance (Xrs at 5 Hz and resonant frequency), and within-breath changes in reactance (Xrs at 5 Hz and resonant frequency) discriminated between patients with COPD and asthma. In multivariate regression analyses, inspiratory-expiratory differences in Xrs at 5 Hz contributed significantly to the differentiation between COPD and asthma, independent of age, gender, body weight, and pulmonary function. CONCLUSION: This new method of FOT is useful in the differential diagnosis of COPD and asthma.

[Leukopenia due to anti-tuberculous chemotherapy including rifampicin and isoniazid].

OBJECTIVES: To examine the incidence rate by age and gender of leukopenia caused by chemotherapy including rifampicin (RFP) and isoniazid (INH), and to study the relationships between the leukopenia and the hepatic side effect or other haematological disorders such as thrombocytopenia. SUBJECTS: Out of the tuberculosis patients who were admitted to our hospital in 1987-88, 1991-92, and 1996-2000, 1,525 patients (1,153 men, 372 women) were chosen for our study who had the white blood cell counts (WBC) in the peripheral blood more than 3,000/mm3 before chemotherapy, and underwent haematologic examination at least twice within 3 months after starting chemotherapy. METHODS: The definition of leukopenia was as follows: 1) WBC became less than 3,000/mm3 during chemotherapy for patients with pre-treatment WBC more than 4,000/mm3, or 2) WBC decreased more than 1,000/mm3 in patients with pre-treatment WBC between 3,000 and 4,000/mm3. The incidence rates of leukopenia by age, gender, and regimens of chemotherapy were calculated. The case-control study was done between the control and the leukopenia groups excluding patients suffered from agranulocytosis to clarify the hematological and biochemical characteristics of the leukopenia group. The control patients were chosen in the following way. For each patient with leukopenia, a patient with the same admission year, same gender, same regimen of chemotherapy, and the nearest age was chosen as a control patient. The changes in counts of white blood cell, granulocyte, and platelet, in hemoglobin concentration, and in hepatic enzyme levels before and during chemotherapy were compared between the leukopenia and the control groups. Thrombocytopenia was defined as platelet count less than 15 x 10(4)/mm3 and hepatic dysfunction as either asparate aminotransferase (AST) higher than 31 IU/l or alanine aminotransferase (ALT) higher than 34 IU/l. RESULTS: (1) Incidence rate of leukopenia The leukopenia appeared in 36 patients (14 men, 22 women), two (one man, one woman) of whom showed agranulocytosis. The incidence rate was 1.2% (14/1,153) for men and 5.9% (22/372) for women. The incidence rate of women was higher than that of men in the age groups between 20 to 79 y.o., but no difference was seen in the age groups elder than 80 y.o. There were no differences in the incidence rate among groups treated with HRE (E: ethambutol), HRS (S: streptomycin), and HREZ (Z: pyrazinamide). The chemotherapy was continued in 30 patients after the appearance of leukopenia, and the natural recovery from leukopenia was seen in 19 patients, while the leukopenic state lasted during the chemotherapy in the remaining 11 patients. In two patients who exhibited agranulocytosis all drugs were discontinued. In the remaining 4 patients one or more drugs were discontinued. (2) Case-control study between leukopenia (N = 34) and the control (N = 34) groups There were no differences in age, sputum culture positivity on admission, degree of roentgenographic extent of the disease, ratio of cavity formation, and quantity of daily doses between the two groups. There was also no difference between the days until leukopenia appeared after starting chemotherapy (47.6 +/- 29.5 days) in the leukopenia group, and the days until WBC count became minimum within 3 months after starting chemotherapy (41.7 +/- 21.0 days) in the control group. The negativity of tuberculin skin testing was higher in the leukopenia group [7/14 (50%)] than in the control group [1/10 (10%)], however, the difference was statistically not significant due to rather small size of cases. Before the starting chemotherapy, the counts of WBC (7,230 +/- 1,530 vs 5,500 +/- 1,510/mm3, p < 0.001), neutrophil (5,230 +/- 1,450 vs 4,320 +/- 1,620/mm3, p < 0.05), lymphocyte (1,440 +/- 830 vs 830 +/- 440/mm3, p < 0.001) and platelet (34.9 +/- 12.2 vs 24.1 +/- 6.4 x 10(4)/mm3, p < 0.001) in the peripheral blood and the globulin level (3.71 +/- 0.61 vs 3.35 +/- 0.61 g/dl, p < 0.05) in the serum were significantly higher in the control group than in the leukopenia group. The decrements in the counts of WBC and granulocyte during chemotherapy were larger in the leukopenia group than in the control group (delta WBC: 2,880 +/- 1,530 vs 1,910 +/- 1,520/mm3, and delta Neut: 2,840 +/- 1,510 vs 1,820 +/- 1,380/mm3, p = 0.01, respectively), but the counts of lymphocyte were similar in both groups. The platelet counts also decreased in both groups, but to the mid-normal level in the control group, and to the lowest normal level in the leukopenia group, in which 15 out of 34 patients (44%) showed thrombocytopenia. The levels in the serum of hepatic enzymes such as AST, ALT, and gamma-GTP (gamma-glutamyl aminotransferase) increased during chemotherapy in the leukopenia group, while decreased in the control group, and the facts indicate that in the former not only bone marrow cells but also hepatic cells were impaired by anti-tuberculosis drugs. CONSIDERATIONS: Leukopenia may occur in the course of treatment with anti-tuberculosis drugs, but it is not necessary to stop the chemotherapy immediately, because the WBC count recovers spontaneously or remains under stable leukopenic state during chemotherapy in most cases. But when leukopenia appears, the peripheral blood counts must be checked cautiously, and the chemotherapy should be stopped if the WBC count progressively decreases. The patients who showed leukopenia due to anti-tuberculosis drugs may have had weaker natural and acquired (cell-mediated) immunologic response to tuberculosis infection, and more vulnerable bone marrow cells and hepatic cells to anti-tuberculosis drugs than the control.

[Agranulocytosis due to anti-tuberculosis drugs including isoniazid (INH) and rifampicin (RFP)--a report of four cases and review of the literature].

We experienced 4 cases of agranulocytosis due to anti-tuberculosis drugs (rifampicin [RFP], isoniazid [INH], ethambutol [EB], streptomycin [SM] or pyrazinamide [PZA]) among some 6,400 tuberculosis patients who underwent chemotherapy over the past 20 years from 1981 to 2002 in our hospital, and the incidence rate of agranulocytosis was estimated at 0.06%. The 4 cases of agranulocytosis were as follows. CASE 1: A 51-year-old woman with right chest pain and fever was admitted to our hospital on Jan 4, 2001. The white blood cell (WBC) count was 5,200/microliter. The tubercle bacilli were cultured in her sputum. The treatment with INH 0.3, RFP 0.45, EB 0.75, PZA 1.2 g/day, allopurinol and teprenone was started on Jan 13. Pyrazinamide and allopurinol were stopped because of hyper-uric acidemia on Feb 7. Agranulocytosis and eosinophilia (WBC 1,300 [Neut 1%, Ly 57%, Eos 35%]) developed on Feb 13. All drugs were withdrawn and G-CSF drug nartograstim 100 micrograms was injected subcutaneously for 3 days. The WBC recovered to normal level and she was thereafter treated with INH, EB and Levofloxacin (LVFX) without any further trouble. Agranulocytosis in this case was supposed to be due to RFP. CASE 2: A 66-year-old man who had had nephrotic syndrome and hypothyroidism and has been treated with prednisolone 10 mg/day was admitted to our hospital on Aug 9, 2000 because of miliary tuberculosis. The tubercle bacilli were cultured in his sputum and the treatment with INH 0.3, RFP 0.45, and EB 0.75 g/day were started on Aug 10, but it was withdrawn on Aug 17 because of general skin eruption. After re-starting treatment with EB and INH on Aug 24, RFP was added in small dosage (0.05 g) on Oct 12, but agranulomatosis (WBC 2,300/microliter [Neut 2%]) developed on Nov 21, and all drugs were withdrawn again. The G-CSF drug filgrastim was used once subcutaneously, and WBC recovered immediately. He was thereafter treated with INH, EB, LVFX successfully. Agranulocytosis was supposed to be due to RFP. CASE 3: A 60-year-old woman without symptoms had abnormal chest roentgenograph, and consulted with our hospital on Aug 26, 2002. The broncho-alveolar lavage fluid was smear and culture-negative, but PCR-TB positive, and the case was diagnosed as pulmonary tuberculosis. Treatment with INH 0.3, RFP 0.45, EB 0.75, PZA 1.2 g/day, alloprinol 300 mg and rebamipide 300 mg/day was started on Sept. 5, 2002. Late in September, she complained of appetite loss. The laboratory data on Oct 3 revealed WBC 900/microliter (Neut 1%, Ly 94%), aspartate aminotransferase (AST) 199 IU/l, and alanine aminotransferase (ALT) 253 IU/l, showing agranulocytosis and drug-induced hepatitis. The chemotherapy was immediately withdrawn and she was admitted to our hospital on the next day. Glycyrrhizin derivative (SNMC) 40 ml was injected for 5 days, and WBC recovered, and AST and ALT also became normal. CASE 4: A 60-year-old man was admitted to our hospital on March 11, 1981 because pulmonary tuberculosis had recurred. He had been treated with SM, PAS and INH in 1973 for pulmonary tuberculosis. On admission examination of blood count and blood chemistry were normal. Treatment with RFP, INH and SM was started on March 11. He stopped out from the hospital on April 17, but in a few days he returned back with sore throat, lower lip swelling and gingival bleeding. Blood cell count on April 24 showed pancytopenia with RBC 226, Hb 7.5, WBC 800 (Ly 96%, Eos 4%) and Plt 10,000/microliter. The bone-marrow showed NCC (nuceated cell count) of 5,500, and megakaryocyte 0. Thereafter ground glass appearance shadows were seen on the whole lung field, and he died May 26. Autopsy showed generalized aspergillosis. It was strongly suspected that either of RFP, INH or SM was responsible for his pancytopenia. We collected another 10 cases of agranulocytosis due to anti-tuberculosis drugs in the world wide literature, and found men/women ratio 5/8 (in one case gender was not known), the duration of chemotherapy before appearance of agranulocytosis 1-3 months, no change in the lymphocyte count of the peripheral blood, and the accompanying of another allergic signs such as skin eruption, blood eosinophilia or drug-induced hepatitis in some cases, and these findings suggest that the mechanism of agranulocytosis due to anti-tuberculosis drugs was allergic in nature.