Yi-Chu Chen

Clinical significance of anti-GM-CSF antibodies in idiopathic pulmonary alveolar proteinosis

Background: The role of anti-granulocyte-macrophage colony stimulating factor (GM-CSF) antibodies as a diagnostic marker in idiopathic pulmonary alveolar proteinosis (iPAP) remains unclear. Methods: Anti-GM-CSF antibodies were detected in blood and bronchoalveolar lavage fluid (BAL) fluid in 13 patients with iPAP. Three patients with secondary PAP, 35 with other pulmonary disorders, and 10 subjects without lung lesions acted as controls. Blood samples only were obtained from 30 healthy medical personnel. Anti-GM-CSF antibodies were detected using immunoblotting and measured semi-quantitatively by serial dilution or concentration methods. The relationship between antibodies and reported severity indicators for iPAP was analysed. Results: Anti-GM-CSF antibodies could be detected in both blood and BAL fluid samples in 12 of 13 iPAP patients and were undetectable in blood and/or BAL fluid from the other subjects studied. BAL fluid levels of anti-GM-CSF antibodies were highly correlated with the severity indicators for iPAP, including serum lactate dehydrogenase (LDH) levels, arterial oxygen tension, alveolar-arterial oxygen tension difference, (AaPo2), lung carbon monoxide transfer factor, and some lesion scores on chest radiographs and computed tomographic scans. In contrast, blood anti-GM-CSF antibodies were not significantly correlated with the severity indicators evaluated. In addition, patients with iPAP who required subsequent therapeutic lung lavage had significantly higher values of serum LDH, AaPO2, and BAL fluid anti-GM-CSF antibodies, and significantly lower values of Pao2. Conclusions: In addition to serum LDH levels, Pao2 and AaPo2, BAL fluid levels of anti-GM-CSF antibodies might reflect disease severity in patients with iPAP and predict the need for subsequent therapeutic lung lavage. These findings may expand the role of anti-GM-CSF antibodies in iPAP.

Effect of Rapid Ascent to High Altitude on Autonomic Cardiovascular Modulation

Background:Effect of acute hypobaric hypoxia on autonomic nervous activities remains unclear. We evaluated the effect of rapid ascent to high altitude on autonomic cardiovascular modulation and compared the differences between the subjects with and without acute mountain sickness (AMS). Method:Twenty-seven unacclimatized healthy subjects were included for this study. The sleep and study altitude (3180 m) was reached by car from low level (555 m) within 3 hours. The stationary spectral heart rate variability was measured 3 days before ascent (T0), 2 nights at high altitude (T1 and T2), and 2 days after descent (T3). AMS occurrence was evaluated by the Lake Louise score system. Results:At high altitude, RR intervals (RRI), standard deviation of RRI (SDRR), total power (TP), low-frequency power (LF), high-frequency power (HF), and normalized HF decreased significantly but normalized LF and LF/HF ratio increased significantly in subjects irrespective of AMS. AMS developed in 13 of 27 (48.1%) subjects. Compared with the data at T1, SDRR, TP, LF, and HF increased at T2 in AMS group but decreased in non-AMS group, and the differences in these variables (data at T2 minus data at T1) between the 2 groups showed statistical significance. Conclusions:After rapid ascent to high altitude, autonomic nervous activities were suppressed and sympathetic activity was relatively predominant. At high altitude, the discordant changes in SDRR, TP, LF, and HF may reflect varying capacity of acute hypobaric hypoxic adaptation between the subjects with and without AMS.

Clinical Importance of Bronchoalveolar Lavage Fluid and Blood Cytokines, Surfactant Protein D, and Kerbs von Lungren 6 Antigen in Idiopathic Pulmonary Alveolar Proteinosis

OBJECTIVE To investigate the clinical importance of cytokines, surfactant protein D (SFTPD, formerly SP-D), and Kerbs von Lungren 6 antigen (KL-6) in bronchoalveolar lavage fluid (BALF) and blood in patients with idiopathic pulmonary alveolar proteinosis (iPAP). PARTICIPANTS AND METHODS Patients with iPAP diagnosed by characteristic cytopathologic examination of BALF and pathologic examination of transbronchial lung biopsy specimens or open lung biopsy specimens were enrolled in the study from January 1, 1995, through June 30, 2005. To investigate the clinical importance of cytokines, SFTPD, and KL-6 in iPAP, we measured tumor necrosis factor superfamily, member 2 (TNF, formerly TNF-α) and interleukin (IL) 1β in BALF and IL-6, IL-10, IL-8, chemokine (C-C motif) ligand 4 (CCL4, formerly MIP-1β), chemokine (C-C motif) ligand 2 (CCL2, formerly MCP-1), SFTPD, and KL-6 in both BALF and blood in 15 patients with iPAP and 48 patients with interstitial lung diseases (diseased controls) (including 20 with interstitial pneumonitis associated with collagen vascular diseases, 13 with idiopathic pulmonary fibrosis, and 15 with sarcoidosis) and 20 individuals without pulmonary diseases (lung controls). RESULTS Patients with iPAP had significantly higher levels of TNF, IL-6, IL-8, CCL4, CCL2, SFTPD, and KL-6 in BALF than did lung controls and had significantly higher levels of CCL4, CCL2, SFTPD, and KL-6 levels in BALF than did diseased controls. Patients with iPAP had significantly higher levels of IL-10, IL-8, CCL2, SFTPD, and KL-6 in blood than did lung controls and significantly higher levels of KL-6 in blood than did diseased controls. Levels of KL-6 both in BALF and blood were significantly correlated with serum lactate dehydrogenase level, arterial oxygen tension, and alveolar-arterial gradient in partial pressure of oxygen, the severity markers for iPAP, and were significantly higher in patients with iPAP who required subsequent therapeutic lung lavage. CONCLUSION Patients with iPAP had elevated levels of SFTPD, KL-6, and cytokines in both BALF and blood. Elevated levels of KL-6 in both BALF and blood may be valuable in reflecting disease severity of patients with iPAP and in determining the need for therapeutic lung lavage.

The role of total bile acid in oral secretions in ventilator-associated pneumonia ☆,☆☆

PURPOSE The aim of this study was to investigate the role of inflammatory biomarkers and total bile acid (TBA) in oral secretions in the development of ventilator-associated pneumonia (VAP). MATERIALS This prospective study was conducted in an intensive care unit. Oral secretions were collected from mechanically ventilated patients who met the selection criteria for VAP prevention protocol. The levels of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor α, soluble intercellular adhesion molecule-1, monocyte chemoattractant protein-1, C-reactive protein, surfactant protein D, and TBA in oral secretions were measured and compared between the patients with and those without VAP. RESULTS Thirty-nine patients with and 39 patients without VAP were studied. The levels of inflammatory biomarkers in oral secretions showed no significant difference between the 2 groups. However, the patients with VAP had significantly higher values of TBA in oral secretions than did those without VAP (median and 25th-75th interquartile range, 9.59 and 1.37-24.66 μmol/L vs 2.74 and 0.00-8.22 μmol/L; P < .003). No significant correlations were found between TBA and inflammatory biomarkers in oral secretions. CONCLUSIONS Duodenogastroesophageal reflux as evidenced by the presence of TBA in oral secretions is common in mechanically ventilated patients and may play a role in the development of VAP.

Recurrence of Pulmonary Arteriovenous Malformations in a Female with Hereditary Hemorrhagic Telangiectasia

&NA; Pulmonary arteriovenous malformations (AVMs) are an uncommon disorder and may cause life‐threatening complications if left untreated. The paucity of good longitudinal data on patients with pulmonary AVMs can be a significant challenge clinically. The authors report a case of recurrence of pulmonary AVMs in a young female with hereditary hemorrhagic telangiectasia (HHT) subjected to transcatheter embolotherapy (TCET) in 1995. Recurrence of pulmonary AVMs was suspected because of marked impairment of oxygenation in 1997 and in 2000, while the patient was pregnant, and later confirmed by imaging studies in early 2003. Despite successful embolization of all visible pulmonary AVMs, contrast echocardiography suggested the presence of intrapulmonary shunt. A shunt of 11.4% was measured using a 100% oxygen test. Loss of flow pattern was the immediate change of pulmonary AVMs after TCET shown by chest sonography. A decrease in the size of the pulmonary AVMs was observed 6 weeks later. This case illustrates the clinical relevance of longitudinal monitoring of arterial blood gases in screening for the recurrence of pulmonary AVMs, particularly in patients with HHT, and the roles of chest sonography and contrast echocardiography in monitoring the efficiency of TCET.

CLINICAL SIGNIFICANCE OF ANTI-GM-CSF ANTIBODIES IN IDIOPATHIC PULMONARY ALVEOLAR PROTEINOSIS

BACKGROUND The role of anti-granulocyte-macrophage colony stimulating factor (GM-CSF) antibodies as a diagnostic marker in idiopathic pulmonary alveolar proteinosis (iPAP) remains unclear. METHODS Anti-GM-CSF antibodies were detected in blood and bronchoalveolar lavage fluid (BAL) fluid in 13 patients with iPAP. Three patients with secondary PAP, 35 with other pulmonary disorders, and 10 subjects without lung lesions acted as controls. Blood samples only were obtained from 30 healthy medical personnel. Anti-GM-CSF antibodies were detected using immunoblotting and measured semi-quantitatively by serial dilution or concentration methods. The relationship between antibodies and reported severity indicators for iPAP was analysed. RESULTS Anti-GM-CSF antibodies could be detected in both blood and BAL fluid samples in 12 of 13 iPAP patients and were undetectable in blood and/or BAL fluid from the other subjects studied. BAL fluid levels of anti-GM-CSF antibodies were highly correlated with the severity indicators for iPAP, including serum lactate dehydrogenase (LDH) levels, arterial oxygen tension, alveolar-arterial oxygen tension difference, (AaPO2), lung carbon monoxide transfer factor, and some lesion scores on chest radiographs and computed tomographic scans. In contrast, blood anti-GM-CSF antibodies were not significantly correlated with the severity indicators evaluated. In addition, patients with iPAP who required subsequent therapeutic lung lavage had significantly higher values of serum LDH, AaPO2, and BAL fluid anti-GM-CSF antibodies, and significantly lower values of PaO2. CONCLUSIONS In addition to serum LDH levels, PaO2 and AaPO2, BAL fluid levels of anti-GM-CSF antibodies might reflect disease severity in patients with iPAP and predict the need for subsequent therapeutic lung lavage. These findings may expand the role of anti-GM-CSF antibodies in iPAP.