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Background The diagnostic yield of bronchoscopy in patients with endoscopically nonvisible (peripheral) tumors varies from 40% to 56%. Increasingly, molecular markers in bronchial washings are being investigated to improve the diagnostic yield. The aim of this study was to analyze the diagnostic value of the Ras association domain family 1A gene (RASSF1A) methylation analysis in washings in nondiagnostic bronchoscopy in the analysis of patients with suspected lung cancer who had peripheral tumors. Furthermore, the additional diagnostic value of Kirsten rat sarcoma 2 viral oncogene homolog ( KRAS ) mutations with RASSF1 methylation was analyzed. Methods From a prospectively collected series, 129 patients with lung cancer and 28 control subjects were analyzed retrospectively regarding the methylation status of the promoter region of the RASSF1A gene by quantitative methylation-specific polymerase chain reaction and KRAS point mutations by using the sensitive Point-EXACCT method. Results A total of 40% of the lung cancer patients had peripheral tumors, and 17 patients had a nondiagnostic bronchoscopy. In these patients, RASSF1A methylation was detected in the washings of four patients (24%), and KRAS mutations were detected in the washings of two patients (12%). In total, 29% of the false-negative or doubtful cytology results were accompanied by RASSF1A methylation or KRAS mutation results that were highly suggestive of malignancy. The proportion of RASSF1A methylation was significantly higher in central and larger tumors. No relevant RASSF1A methylation was detected in control samples. Conclusions Our data suggest that the molecular analysis of two biomarkers in nondiagnostic bronchial washings may better guide diagnostic procedures in patients with suspected lung cancer.

Background One of the contributors to exercise limitation in COPD is dynamic hyperinflation. Although dynamic hyperinflation appears to occur during several exercise protocols in COPD and seems to increase with increasing disease severity, it is unknown whether dynamic hyperinflation occurs at different severity stages according to the Global initiative for chronic Obstructive Lung Disease (GOLD) in daily life. The present study, therefore, aimed to compare dynamic hyperinflation between COPD GOLD stages II-IV during daily activities. Methods Thirty-two clinically stable patients with COPD GOLD II (n = 10), III (n = 12), and IV (n = 10) participated in this study. Respiratory physiology during a daily activity was measured at patients' homes with Oxycon Mobile. Inspiratory capacity maneuvers were performed at rest, at 2-min intervals during the activity, and at the end of the activity. Change in inspiratory capacity is commonly used to reflect change in end-expiratory lung volume (ΔEELV) and, therefore, dynamic hyperinflation. The combination of static and dynamic hyperinflation was reflected by inspiratory reserve volume (IRV) during the activity. Results Overall, increase in EELV occurred in GOLD II-IV without significant difference between the groups. There was a tendency for a smaller ΔEELV in GOLD IV. ΔEELV was inversely related to static hyperinflation. IRV during the daily activity was related to the level of airflow obstruction. Conclusions Dynamic hyperinflation occurs independent of GOLD stage during real-life daily activities. The combination of static and dynamic hyperinflation, however, increases with increasing airflow obstruction.

The diagnostic yield of bronchoscopy in patients with endoscopically nonvisible (peripheral) tumors varies from 40% to 56%. Increasingly, molecular markers in bronchial washings are being investigated to improve the diagnostic yield. The aim of this study was to analyze the diagnostic value of the Ras association domain family 1A gene (RASSF1A) methylation analysis in washings in nondiagnostic bronchoscopy in the analysis of patients with suspected lung cancer who had peripheral tumors. Furthermore, the additional diagnostic value of Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutations with RASSF1 methylation was analyzed.From a prospectively collected series, 129 patients with lung cancer and 28 control subjects were analyzed retrospectively regarding the methylation status of the promoter region of the RASSF1A gene by quantitative methylation-specific polymerase chain reaction and KRAS point mutations by using the sensitive Point-EXACCT method.A total of 40% of the lung cancer patients had peripheral tumors, and 17 patients had a nondiagnostic bronchoscopy. In these patients, RASSF1A methylation was detected in the washings of four patients (24%), and KRAS mutations were detected in the washings of two patients (12%). In total, 29% of the false-negative or doubtful cytology results were accompanied by RASSF1A methylation or KRAS mutation results that were highly suggestive of malignancy. The proportion of RASSF1A methylation was significantly higher in central and larger tumors. No relevant RASSF1A methylation was detected in control samples.Our data suggest that the molecular analysis of two biomarkers in nondiagnostic bronchial washings may better guide diagnostic procedures in patients with suspected lung cancer.

One of the contributors to exercise limitation in COPD is dynamic hyperinflation. Although dynamic hyperinflation appears to occur during several exercise protocols in COPD and seems to increase with increasing disease severity, it is unknown whether dynamic hyperinflation occurs at different severity stages according to the Global initiative for chronic Obstructive Lung Disease (GOLD) in daily life. The present study, therefore, aimed to compare dynamic hyperinflation between COPD GOLD stages II-IV during daily activities.Thirty-two clinically stable patients with COPD GOLD II (n = 10), III (n = 12), and IV (n = 10) participated in this study. Respiratory physiology during a daily activity was measured at patients' homes with Oxycon Mobile. Inspiratory capacity maneuvers were performed at rest, at 2-min intervals during the activity, and at the end of the activity. Change in inspiratory capacity is commonly used to reflect change in end-expiratory lung volume (DeltaEELV) and, therefore, dynamic hyperinflation. The combination of static and dynamic hyperinflation was reflected by inspiratory reserve volume (IRV) during the activity.Overall, increase in EELV occurred in GOLD II-IV without significant difference between the groups. There was a tendency for a smaller DeltaEELV in GOLD IV. DeltaEELV was inversely related to static hyperinflation. IRV during the daily activity was related to the level of airflow obstruction.Dynamic hyperinflation occurs independent of GOLD stage during real-life daily activities. The combination of static and dynamic hyperinflation, however, increases with increasing airflow obstruction.

The effects of additional target-flow inspiratory muscle training (TF-IMT) on the performance of the inspiratory muscles, on general exercise capacity, and on psychologic parameters during a pulmonary rehabilitation program (PR) were studied in 40 patients with COPD selected for ventilatory limitation during exercise. The mean age of the patients was 59 years, and the mean FEV 1 was approximately 50 percent of predicted. All patients participated in a ten-week PR program. They were randomized to receive either additional TF-IMT (PR + IMT) or not (PR). The TF-IMT was performed by means of a target-flow resistive device; the generated mouth pressure and the duration of inspiration and of the respiratory cycle were imposed. After the training period, maximal inspiratory mouth pressure and EMC-fatigability of the diaphragm were significantly better in the PR + IMT group than in the PR group. Maximal work load and psychologic symptoms increased to the same extent in both groups. The 12-minute walking distance also increased in both groups, but it increased significantly more in the PR + IMT group than in the PR group. We believe that additional TF-IMT during PR in a selected group of patients with COPD who have ventilatory limitation has an extra beneficial effect on the performance of the inspiratory muscles and on exercise performance. (Chest 1991; 99:128–33)