Corrigendum: Oxygen Extraction Based on Inspiratory and Expiratory Gas Analysis Identifies Ventilatory Inefficiency in Chronic Obstructive Pulmonary Disease.

[This corrects the article DOI: 10.3389/fphys.2021.703977.].

Oxygen Extraction Based on Inspiratory and Expiratory Gas Analysis Identifies Ventilatory Inefficiency in Chronic Obstructive Pulmonary Disease.

Aims: In contrast to cardiovascular disease, low rather than high ventilatory inefficiency, evaluated by the minute ventilation-carbon dioxide output (V'E-V'CO2)-slope, has been recognized as being related to greater disease severity in chronic obstructive pulmonary disease (COPD). To better care for patients with cardiopulmonary disease, understanding the physiological correlation between ventilatory inefficiency and exercise limitation is necessary, but remains inadequate. Given that oxygen uptake (V'O2) evaluated by cardiopulmonary exercise testing (CPET) depends on both the ventilatory capability and oxygen extraction, i.e., the difference between inspiratory and expiratory oxygen concentration (ΔFO2), the aim of this study was to investigate the correlations between V'E-V'CO2-slope and the ΔFO2 during exercise and their physiological implications in patients with COPD. Methods: A total of 156 COPD patients (mean age, 70.9 ± 7.2 years) with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I-IV and 16 controls underwent CPET with blood gas analysis. Results: With the progression of COPD, mechanical ventilatory constraints together with a slower respiratory frequency led to exertional respiratory acidosis. In GOLD IV cases, (1) decrease in the dependence of reduced peak V'O2 on V'E led to an increase in its dependence on peak ΔFO2 during exercise; and (2) the ΔFO2-V'CO2-slope became steeper, correlating with the severity of exertional respiratory acidosis (r = 0.6359, p < 0.0001). No significant differences in peak exercise ΔFO2 or V'E-V'CO2-slope were observed among the various GOLD stages. In all subjects, including controls, peak exercise ΔFO2 had the strongest correlation with the V'E-V'CO2-slope (r = -0.8835, p < 0.0001) and correlated well with body mass index (r = 0.3871, p < 0.0001), although it did not correlate with the heart rate-V'CO2-relationship and V'E. Conclusions: Ventilatory efficiency related to CO2 clearance might depend on exertional oxygen extraction in the body. Measuring ΔFO2 might be a key component for identifying ventilatory inefficiency and oxygen availability. Increasing ΔFO2 would help to improve ventilatory inefficiency and exercise tolerance separately from cardiac and ventilatory capability in COPD patients.

Human airway trypsin-like protease enhances interleukin-8 synthesis in bronchial epithelial cells by activating protease-activated receptor 2.

Human airway trypsin-like protease (HAT) localizes at human bronchial epithelial cells (HBECs). HAT enhanced release of interleukin-8 (IL-8) from HBECs at 10-100 mU/mL and the enhanced release was almost completely abolished by 50 µM leupeptin, a serine protease inhibitor. Previous reports suggested that HAT displays its physiological functions via protease-activated receptor 2 (PAR2). In the present study, we examined the mechanism whereby HAT upregulates IL-8 synthesis in HBECs with a focus on PAR2. Northern blot analysis revealed that HAT enhanced IL-8 mRNA expression at concentrations of 10-100 mU/mL. PAR2 activating peptide (PAR2 AP) also enhanced IL-8 release and IL-8 mRNA expression in HBECs at 50-1,000 µM at similar levels as HAT. Knockdown of PAR2 mRNA by siRNA methods showed that PAR2 mRNA expression was significantly depressed in primary HBECs, and both HAT- and PAR2 AP-induced IL-8 mRNA elevation was significantly depressed in PAR2 siRNA-transfected HBECs. Additionally, HAT cleaved the PAR2 activating site (R36-S37 bond) of synthetic PAR2 N-terminal peptide. These results indicate that HAT stimulates IL-8 synthesis in airway epithelial cells via PAR2 and could help to amplify inflammation in chronic respiratory tract disease.

Randomized, dose-finding trial of ghrelin treatment for chronic respiratory failure.

OBJECTIVES: Ghrelin, a growth hormone-releasing peptide, has shown efficacy in chronic obstructive pulmonary disease (COPD) patients in previous trials. This study was designed to evaluate the effective dose of ghrelin in chronic respiratory failure patients. METHODS: In this randomized, double-blind, dose-finding, single-center study, 18 patients, including 16 with COPD, were randomly assigned to receive pulmonary rehabilitation (PR) with intravenous ghrelin at 1 µg/kg or 2 µg/kg, twice daily for 3 weeks. The primary outcome was the change in peak oxygen uptake ( V˙o2). Secondary outcomes included changes in plasma vascular endothelial growth factor (VEGF)-A levels, and exertional cardio-respiratory functions with blood gas analysis. RESULTS: With incremental exercise, there was no significant differences in the mean difference (high-dose ghrelin minus low-dose ghrelin) of peak V˙o2 (1.0 mL/kg/min, 95% CI: -0.6 to 2.6 mL/kg/min, between-group, P = 0.193). However, there were significant differences in the mean difference of (i) O2 -pulse (0.6 mL/beats, 95% CI: 0.0 to 1.1 mL/beats, between-group, P = 0.035) at iso-time; and ii) PaO2 (4.2 mmHg, 95% CI: 0.2 to 8.2 mmHg, between-group, P = 0.041) and PaCO2 (-3.1 mmHg, 95% CI: -6.0 to -0.3 mmHg, between-group, P = 0.034) at peak exercise. The mean difference in the plasma VEGF-A level was significantly inhibited by high dose-ghrelin with PR (-125.4 pg/mL, 95% CI: -235.2 to -15.5 pg/mL, between-group, P = 0.028). CONCLUSION: Although the primary outcome of the study was not met, high-dose ghrelin with PR improved exertional cardiac function and blood gas values, and inhibited circulating VEGF-A levels.

[Nutrition management for COPD].

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory reaction of the lung and of the whole body, and pulmonary cachexia often occurs during the advanced stage. The effects of nutritional support upon the management of under-nutrition in COPD remain controversial. However, a study of the effects of nutritional supplement therapy upon such patients with COPD has recently been published. The present report comprises a review of recent articles about the nutritional support of patients with COPD, especially those with cachexia, and a discussion about the roles of nutritional supplement therapy, focusing on exercise and treatment with ghrelin and vitamin D in the management of COPD.

[THE GENETIC EXAMINATION OF BRONCHIAL LAVAGE ENABLES THE PROMPT DIAGNOSIS OF PULMONARY MYCOBACTERIUM KANSASII--A CASE REPORT].

A 59-year-old man with chronic obstructive pulmonary disease and bronchial asthma presented at our hospital with an abnormal shadow on the chest radiograph, which was obtained as part of a routine medical examination. Computed tomography of the chest revealed two nodules in the right upper lung with the longest diameter measuring 29 mm and 10 mm, respectively. A granulomatous disease was strongly suspected based on the histological features of the transbronchial lung biopsy specimen. Results of smear examination for mycobacteria and genetic examination of the bronchial lavage aspirate by the transcription reverse transcription concerted (TRC) reaction method for Mycobacterium tuberculosis and M. avium complex (MAC), were both negative. However, three days after the bronchoscopic examination, an additional genetic examination by the TRC method confirmed the diagnosis of M. kansasii infection. About two weeks later, the culture results were positive and M. kansasii infection was re-confirmed with the DNA probe method. The patient responded well to treatment with a combination of isoniazid, rifampicin, and ethambutol. In Japan, among the nontuberculous mycobacterial infections, the prevalence of pulmonary M.kansasii disease is second only to infection with MAC. However, it is often difficult to distinguish this disease from pulmonary tuberculosis. In this patient, a genetic examination with the TRC method enabled a prompt diagnosis of M. kansasii infection. The TRC method appears to be a useful tool for diagnosing nontubercular mycobacterial infections.

Exogenous lipoid pneumonia caused by repeated sesame oil pulling: a report of two cases.

BACKGROUND: Exogenous lipoid pneumonia is a rare disease caused by aspiration or inhalation of oily substances. CASE PRESENTATION: A 66-year-old male with dry cough (Case 1) and a 38-year-old female with shortness of breath (Case 2) demonstrated ground-glass opacities on chest computed tomography and were diagnosed with lipoid pneumonia based on the confirmation of lipid-laden alveolar macrophages. Both patients habitually performed sesame oil pulling via nasal or mouth washing for several months prior to the diagnosis. CONCLUSION: Steroid therapy and bronchoalveolar lavage resulted in improvement in Case 1, and no intensive therapy was required for Case 2. Sesame oil pulling has been rarely been reported to cause lipoid pneumonia.

Personalized pulmonary rehabilitation and occupational therapy based on cardiopulmonary exercise testing for patients with advanced chronic obstructive pulmonary disease.

TAKE-HOME SUMMARY: Personalized pulmonary rehabilitation including occupational therapy improves the prognosis of patients with advanced COPD. PURPOSE: We previously reported that patients with chronic obstructive pulmonary disease (COPD) exhibit three exercise-induced life-threatening conditions: hypoxemia, sympathetic overactivity, and respiratory acidosis. We aimed to verify whether mortality in patients with advanced COPD could be reduced by a personalized pulmonary rehabilitation (PPR) program in hospital, which determines individual safe ranges and includes occupational therapy (PPR-OT), to prevent desaturation and sympathetic nerve activation during daily activities. PATIENTS AND METHODS: The novel PPR-OT program was evaluated in a retrospective study of patients with COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] Grade D) who underwent cardiopulmonary exercise testing (CPET) between April 1990 and December 1999. They received regular treatment without the proposed therapy (control group: n=61; male-to-female ratio [M:F] =57:4; mean age: 68.5±6.7 years) or with the proposed therapy (PPR-OT group: n=46; M:F =44:2; mean age: 68.7±7.1 years). A prospective observational study included patients with COPD receiving home oxygen therapy (HOT) between April 1995 and March 2007 to compare the survival rates of the control group (n=47; M:F ratio =34:13; mean age: 71.3±10.0 years) and the PPR-OT group (n=85; M:F =78:7; mean age: 70.7±6.1 years) who completed the proposed therapy. Survival after CPET or HOT was analyzed using Cox proportional-hazards regression and Kaplan-Meier analyses. RESULTS: In both studies, the program significantly improved all-cause mortality (retrospective study: risk ratio =0.389 [range: 0.172-0.800]; P=0.0094; log-rank test, P=0.0094; observational study: risk ratio =0.515 [range: 0.296-0.933]; P=0.0291; log-rank test, P=0.0232]. At 5 years and 7 years, all-cause mortality was extremely low in patients in the PPR-OT group receiving HOT (18.8% and 28.2%, respectively), compared to that in the control group (34.0% and 44.7%, respectively). Survival of patients with life-threatening pathophysiological conditions also greatly improved. CONCLUSION: The PPR-OT program improved the survival of patients with advanced COPD probably because it modified life-threatening conditions.

Ghrelin administration for chronic respiratory failure: a randomized dose-comparison trial.

BACKGROUND: Repeated ghrelin administration leads to improvements in symptoms, muscle wasting and exercise tolerance in cachectic patients with pulmonary disease. We investigated the optimal ghrelin dose for underweight patients with chronic respiratory failure. METHODS: In this multicenter, randomized, dose-comparison exploratory study, 44 cachectic patients with chronic respiratory failure were randomly assigned pulmonary rehabilitation with intravenous twice-daily administration of 1 or 2 µg/kg ghrelin for 3 weeks. The primary endpoint was improvement in 6-min walking distance (6 MWD). The secondary endpoint was change in peak VO2. RESULTS: Twenty-one patients were assigned to the 1 µg/kg ghrelin group and 23 to the 2 µg/kg ghrelin group. Change from baseline 6 MWD after treatment was similar between groups(1 µg/kg: 53.9 m, 2 µg/kg: 53.9 m, p = 0.99). Mean change in peak VO2 was significantly greater in the 2 µg/kg group (63.1 ml/min) than in the 1 µg/kg group (-63.8 ml/min, p = 0.048). Food intake and lean body mass significantly increased in both groups, and the St. George Respiratory Questionnaire score, body weight, and body mass index were remarkably improved in only the 2 µg/kg group, although there was no significant difference between groups. No treatment-related serious events were reported for either group. CONCLUSION: Improvements in the oxygen uptake capacity were greater in patients receiving 2 µg/kg ghrelin twice daily for 3 weeks than in those receiving 1 µg/kg, although exercise tolerance was similar between groups at the end of the 3-week treatment period. Thus, a twice daily dose of 2 µg/kg ghrelin is recommended over 1 µg/kg ghrelin for patients with chronic respiratory failure and weight loss.

Pulmonary disease caused by rapidly growing mycobacteria: a retrospective study of 44 cases in Japan.

BACKGROUND: The features of pulmonary disease caused by rapidly growing mycobacteria (RGM) have not been sufficiently documented. OBJECTIVES: To establish these features, we retrospectively evaluated 44 patients. METHODS: We screened respiratory isolates at the National Toneyama Hospital (Osaka, Japan) between 2003 and 2007. Diagnosis was based on the latest guidelines of the American Thoracic Society. The patients were classified into 3 types according to their radiographic findings: fibrocavitary, nodular bronchiectatic and unclassified variant. RESULTS: We obtained 1,348 nontuberculous mycobacteria respiratory isolates from 1,187 patients, including 119 RGM isolates from 100 patients. Forty-four of these 100 patients were definitively diagnosed with respiratory disease due to RGM. The most common pathogen was Mycobacterium abscessus, which accounted for 65.9% of cases, followed by Mycobacterium fortuitum at 20.5%. There was a statistically significant difference in smoking history between patients infected with these 4 RGM species (excluding those with an unknown smoking history; p = 0.039). The overall evaluation of radiographic findings revealed 18.2% as fibrocavitary, 43.2% as nodular bronchiectatic and 38.6% as unclassified variants in these 44 patients. There was a significant difference in radiographic findings between the 4 RGM species (p = 0.002). There was also a significant difference in radiographic findings between M. abscessus and M. fortuitum infected patients (p = 0.022). CONCLUSIONS: Patients with M. abscessus seem to have less of a smoking history and more frequent nodular bronchiectatic radiographic patterns than patients with M. fortuitum. In contrast, fibrocavitary patterns might be more frequent with M. fortuitum infection.

Antigen 85A and mycobacterial DNA-binding protein 1 are targets of immunoglobulin G in individuals with past tuberculosis.

Development of accurate methods for predicting progression of tuberculosis (TB) from the latent state is recognized as vitally important in controlling TB, because a majority of cases develop from latent infections. Past TB that has never been treated has a higher risk of progressing than does latent Mycobacterium tuberculosis infection in patients who have previously received treatment. Antibody responses against 23 kinds of M. tuberculosis proteins in individuals with past TB who had not been medicated were evaluated. These individuals had significantly higher concentrations of antibodies against Antigen 85A and mycobacterial DNA-binding protein 1 (MDP1) than did those with active TB and uninfected controls. In addition, immunohistochemistry revealed colocalization of tubercle bacilli, antigen 85 and MDP1 inside tuberculous granuloma lesions in an asymptomatic subject, showing that M. tuberculosis in lesions expresses both antigen 85 and MDP1. Our study suggests the potential usefulness of measuring antibody responses to antigen 85A and MDP1 for assessing the risk of TB progression.

Exertional acidotic responses in idiopathic pulmonary fibrosis: the mechanisms of exertional dyspnea.

To understand the mechanism of exertional dyspnea, we postulated that, despite hyperoxia during exercise, patients with idiopathic pulmonary fibrosis (IPF) might not regulate exertional acidosis by ventilatory compensation to stop exercise. The exercise responses during 30% O(2) or compressed air (CA) were examined in 13 patients with IPF. The PaO(2), PaCO(2), and HCO(3)(-) levels were higher during exercise with hyperoxia than with CA. At peak exercise, hyperoxia reduced the plasma lactate level. The dyspnea-ratio (%) of the ΔV(O(2)) (peak minus resting oxygen uptake) curve reached a break point that occurred at a similar exercise point with hyperoxia and CA, preceded by a break point in the breathing frequency-ratio of the ΔV(O(2)). Accordingly, the dyspnea score and pH each reached similar levels with hyperoxia and CA to stop exercise. Regardless of breathing CA or 30% O(2), IPF patients did not regulate exertional acidosis by ventilatory compensation to stop exercise, resulting in reaching a specific pH.

Whole-genome sequence of the hypervirulent clinical strain Mycobacterium intracellulare M.i.198.

We report herein the draft genome sequence of Mycobacterium intracellulare clinical strain M.i.198, which consistently exhibits hypervirulence in human patients, human macrophages in vitro, and immunocompetent mice.

Effects of inhaled tiotropium on left ventricular diastolic function in chronic obstructive pulmonary disease patients after pulmonary resection.

PURPOSE: The objective of the present study was to evaluate the effects of inhaled tiotropium on pulmonary function and left ventricular diastolic function in chronic obstructive pulmonary disease patients ≥ 1 year after pulmonary resection for lung cancer. METHODS: This prospective single-arm analysis involved 21 chronic obstructive pulmonary disease patients who underwent pulmonary resection for lung cancer at least one year earlier. Blood pressures, heart rate, spirometry, transthoracic echocardiography including tissue Doppler imaging, and quality of life were evaluated prior to and after 3 months of inhaled tiotropium treatment. B-type natriuretic peptide, white blood cell counts, and C-reactive protein levels before and after inhaled tiotropium treatment were also examined. RESULTS: There were no significant differences between before and after treatment in forced vital capacity and left ventricular ejection fraction. Forced expiratory volume in 1 second and early transmitral velocity/tissue Doppler mitral annular early diastolic velocity values improved from 1.60 ± 0.5 L and 8.97 ± 1.6, respectively, before treatment, to 1.84 ± 0.5 L and 7.59 ± 1.4, respectively, 3 months after treatment (P <0.001). CONCLUSION: Treatment with inhaled tiotropium may be effective in improving not only pulmonary function but also left ventricular diastolic function of patients with chronic obstructive pulmonary disease in the chronic phase after pulmonary resection.

Ghrelin treatment of cachectic patients with chronic obstructive pulmonary disease: a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Pulmonary cachexia is common in advanced chronic obstructive pulmonary disease (COPD), culminating in exercise intolerance and a poor prognosis. Ghrelin is a novel growth hormone (GH)-releasing peptide with GH-independent effects. The efficacy and safety of adding ghrelin to pulmonary rehabilitation (PR) in cachectic COPD patients were investigated. METHODOLOGY/PRINCIPAL FINDINGS: In a multicenter, randomized, double-blind, placebo-controlled trial, 33 cachectic COPD patients were randomly assigned PR with intravenous ghrelin (2 µg/kg) or placebo twice daily for 3 weeks in hospital. The primary outcomes were changes in 6-min walk distance (6-MWD) and the St. George Respiratory Questionnaire (SGRQ) score. Secondary outcomes included changes in the Medical Research Council (MRC) scale, and respiratory muscle strength. At pre-treatment, serum GH levels were increased from baseline levels by a single dose of ghrelin (mean change, +46.5 ng/ml; between-group p<0.0001), the effect of which continued during the 3-week treatment. In the ghrelin group, the mean change from pre-treatment in 6-MWD was improved at Week 3 (+40 m, within-group p = 0.033) and was maintained at Week 7 (+47 m, within-group p = 0.017), although the difference between ghrelin and placebo was not significant. At Week 7, the mean changes in SGRQ symptoms (between-group p = 0.026), in MRC (between-group p = 0.030), and in maximal expiratory pressure (MEP; between-group p = 0.015) were better in the ghrelin group than in the placebo group. Additionally, repeated-measures analysis of variance (ANOVA) indicated significant time course effects of ghrelin versus placebo in SGRQ symptoms (p = 0.049) and MEP (p = 0.021). Ghrelin treatment was well tolerated. CONCLUSIONS/SIGNIFICANCE: In cachectic COPD patients, with the safety profile, ghrelin administration provided improvements in symptoms and respiratory strength, despite the lack of a significant between-group difference in 6-MWD. TRIAL REGISTRATION: UMIN Clinical Trial Registry C000000061.

Efficacy of low-dose landiolol, an ultrashort-acting ß-blocker, on postoperative atrial fibrillation in patients undergoing pulmonary resection for lung cancer.

PURPOSE: Postoperative atrial fibrillation is the most common complication encountered during the early postoperative period following a pulmonary resection procedure. Landiolol is a newly developed, ultrashortacting, ß-adrenoceptor antagonist. The objective of the present study was to evaluate the efficacy and safety of low-dose landiolol for postoperative atrial fibrillation in patients undergoing pulmonary resection for lung cancer. METHODS: Of 553 patients who underwent an elective pulmonary resection procedure for lung cancer at National Toneyama Hospital from January 2005 to December 2009, this analysis involved 30 consecutive patients who developed atrial fibrillation after surgery and needed treatment. These patients were divided into two groups: the landiolol group (n = 15) and the historical control group (treated with a combination of verapamil and digoxin, n = 15). Hemodynamic changes before and 30 min, 2 h, and 12 h after medication, the time required to restore sinus rhythm, and adverse events were evaluated. RESULTS: There were no significant differences between the two groups regarding blood pressure before and after medication. Heart rate was reduced immediately in both groups after medication and was significantly lower in the landiolol group than in the control group. The time to restore sinus rhythm was significantly shorter in the landiolol group than in the control group (8.1 ± 11.0 h vs. 23.0 ± 26.0 h, P < 0.05). In none of the subjects with the landiolol infusion was it discontinued because of side effects. CONCLUSION: Low-dose landiolol can be effective quickly and used safely in patients who develop atrial fibrillation after pulmonary resection for lung cancer.

[Smoking cessation].

Smoking has been determined as a cause of chronic obstructive pulmonary disease (COPD) in most patients. Smoking cessation should be stressed above everything else for COPD patients under all conditions. A smoking habit is determined not as a preference but as a dependency on tobacco; therefore, smoking cessation is difficult solely based on one's motivation. Smoking cessation therapy is employed with cessation aids. Now, we can use nicotine-containing gum, patches, and the nicotine-receptor partial agonist varenicline. First, nicotine from tobacco is replaced with a nicotin patch, or a nicotine-free condition is induced by varenicline. Subsequently, the drugs are gradually reduced. In Japan, smoking cessation therapy is covered by public health insurance as definite requirements.

Predictive value of preoperative tissue Doppler echocardiographic analysis for postoperative atrial fibrillation after pulmonary resection for lung cancer.

OBJECTIVE: The objective of the present study was to evaluate the utility of tissue Doppler imaging for predicting the development of postoperative atrial fibrillation. METHODS: In this prospective observational study, we evaluated 126 patients with lung cancer who underwent a lobectomy during the 18-month period from August 2007 to January 2009. Preoperative evaluations for all patients included tissue Doppler imaging in addition to conventional echocardiographic analysis. The study end point was the development of postoperative atrial fibrillation. RESULTS: Postoperative atrial fibrillation was identified in 29 (23%) patients, in whom significantly higher early transmitral velocity/tissue Doppler mitral annular early diastolic velocity values were noted compared with those seen in patients without atrial fibrillation (9.76 ± 2.3 vs 7.14 ± 1.7, P < .0001). The area under the receiver operating characteristic curve for early transmitral velocity/tissue Doppler mitral annular early diastolic velocity to predict postoperative atrial fibrillation after pulmonary resection for lung cancer was 0.83 (95% confidence interval, 0.74-0.92; P < .001). An early transmitral velocity/tissue Doppler mitral annular early diastolic velocity value of greater than 8 had a sensitivity of 90% and a specificity of 73% for predicting postoperative atrial fibrillation. CONCLUSIONS: Postoperative atrial fibrillation after pulmonary resection might be associated with left ventricular diastolic dysfunction before surgical intervention revealed by using tissue Doppler imaging. Additional studies to establish the significance of tissue Doppler imaging as a tool to predict postoperative atrial fibrillation could contribute to improvements in lung cancer treatments.

Predictive value of B-type natriuretic peptide for postoperative atrial fibrillation following pulmonary resection for lung cancer.

OBJECTIVE: To evaluate the usefulness of atrial natriuretic peptide (ANP) and brain B-type natriuretic peptide (BNP) for predicting postoperative atrial fibrillation (AF), we determined the changes in perioperative ANP and BNP levels in patients undergoing pulmonary resection for lung cancer. METHODS: This prospective observational study was conducted during the 10-month period from July 2007 to April 2008. Eighty patients with lung cancer underwent lobectomy, segmentectomy or wedge resection. Preoperative evaluations included spirometry and examinations of plasma ANP and BNP-levels, which were also determined on postoperative days 1, 3 and 7. RESULTS: Postoperative AF was identified in 22 (28%) of the patients, and those had significantly higher preoperative ANP and BNP levels as compared with patients without AF. During the postoperative course, patients with postoperative AF also had significantly higher ANP and BNP-levels. The area under the receiver-operating characteristic curve for BNP to predict postoperative AF following pulmonary resection for lung cancer was 0.90 (95% confidence interval (CI), 0.82-0.98; p<0.001). A BNP value of 30pgml(-1) had a sensitivity of 77% and a specificity of 93% for predicting postoperative AF following pulmonary resection for lung cancer. CONCLUSIONS: Preoperative BNP level seems to be an appropriate predictor of AF after pulmonary resection.

Acidosis and raised norepinephrine levels are associated with exercise dyspnoea in idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Exertional dyspnoea limits patients with IPF in their activities of daily living. The mechanism, however, has not been elucidated. This study tested the hypothesis in IPF that exertional dyspnoea correlates with cardiopulmonary exercise responses, specifically changes in arterial blood pH and plasma norepinephrine (NE). METHODS: Cardiopulmonary exercise testing with measurements of dyspnoea (Borg scale), plasma NE, plasma lactate and arterial blood gases were performed in 29 patients with IPF and in nine controls. RESULTS: Both groups showed obvious break points in dyspnoea changes during exercise. In IPF, an abrupt change in the Borg scale, pH, PaCO(2) and plasma NE occurred in the late exercise phase after the 'break point'. Compared with controls, patients with IPF had significantly higher HCO(3)(-) levels and physiologic dead space/tidal volume during exercise. In IPF, during both exercise phases, the dyspnoea slope (DeltaBorg scale/Deltaminute ventilation) correlated with the pH slope (DeltapH/Deltaoxygen uptake) (before the break point: r = -0.537, P = 0.0022; r = -0.886, P < 0.0001, after the break point) and the NE slope (DeltaNE/Deltaoxygen uptake) (before the break point: r = 0.481, P = 0.0075; R = 0.784, P < 0.0001, after the break point). CONCLUSIONS: In patients with IPF, exercise-induced acidosis and increases in circulating NE levels were associated with intensity of exertional dyspnoea.