Temporal changes in biomarkers in individuals with and without acute mountain sickness following rapid ascent.

BACKGROUND: Field studies have reported conflicting results regarding changes in biomarkers at high altitude. This study measured temporal changes in biomarkers and compared the differences between individuals with and without acute mountain sickness (AMS). MATERIALS AND METHODS: This study included 34 nonacclimatized healthy participants. Ten-milliliters of blood were collected at four time points: 3 days before ascent (T0), on two successive nights at 3150 m (T1 and T2), and 2 days after descent (T3). Participants were transported by bus from 555 m to 3150 m within 3 hours. AMS was diagnosed using the self-reported Lake Louise Scoring (LLS) questionnaire. RESULTS: Compared with T0, significant increases in E-selectin and decreases in vascular endothelial growth factor (VEGF) levels were observed at high altitude. Significantly increased C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), and S100 calcium-binding protein B (S100B) levels were observed at T2, and significantly decreased vascular cell adhesion molecule-1 (VCAM-1) levels were observed at T3. Eighteen (53%) participants developed AMS. Changes in E-selectin, CRP, MCP-1, and S100B levels were independent of AMS. Relative to individuals without AMS, those with AMS had significantly higher atrial natriuretic peptide (ANP) and VCAM-1 levels and lower plasminogen activator inhibitor-1 (PAI-1) levels at T1 and higher brain natriuretic peptide and lower VEGF and PAI-1 levels at T3. LLSs were positively correlated with ANP and VCAM-1 levels and negatively correlated with PAI-1 levels measured at T1. CONCLUSIONS: After acute ascent, individuals with and without AMS exhibited different trends in biomarkers associated with endothelial cell activation and natriuretic peptides.

Artificial stone-associated silicosis with concurrent Cryptococcus infection.

Acute silicoproteinosis is a disease that develops in weeks, and lasting for years, after massive exposure to silica dust in relatively closed spaces. It was rare, but the cases have recently increased worldwide due to the development of artificial stone industry. Compared with traditional silicosis, artificial stone-associated silicosis is more rapidly progressive and lethal. Hence, a correct diagnosis and optimal treatment are crucial. Here, we present the clinical course of a 33-year-old artificial stonemason who suffered from acute silicoproteinosis with concurrent Cryptococcus infection resulting in profound respiratory failure. This patient was treated by bronchoscope-assisted therapeutic segmental lung lavage and antifungal agent, under mechanical ventilator and ECMO support and recovered well. A brief review of acute silicoproteinosis and artificial stone-associated silicosis is also presented and highlights the new form of industry exposure to silica.

Clinical usefulness of bronchoalveolar lavage in patients with interstitial lung diseases: a pilot study.

BACKGROUND: Bronchoalveolar lavage (BAL) is a useful tool in the diagnostic work-up of patients with interstitial lung diseases (ILDs). In this prospective study, we investigated the clinical usefulness of BAL in patients with ILD radiographically. METHODS: The enrolled patients were classified into outpatient department (OPD), and inpatients groups who was admitted to general ward (GW) or intensive care unit (ICU) groups based on the time when BAL done. The clinical usefulness of BAL was defined as a new diagnosis established and/or treatment significantly changed. The clinical usefulness of BAL among the three groups of patients and the patients divided by underlying diseases was compared using the χ2 test with or without Fisher's exact test. RESULTS: Among our 184 patients, there were 37 in OPD group, 86 in GW group and 61 in ICU group. The final diagnoses were infectious in 23, non-infectious in 102, mixed etiologies in 19, and non-diagnostic in 40 patients. The diagnostic yields (revised diagnosis after BAL) of BAL among ICU patients, GW patients and OPD patients were 60.6%, 69.7% and 21.6%, respectively (P<0.001), and was 57.1% in total patients. The diagnostic yields of BAL among patients with cancer, organ transplantation and collagen vascular disease were statistically different (P=0.009). CONCLUSIONS: BAL is of use in establishing a diagnosis of ILD and is mandatary especially in the admitted patients with ILD because diagnostic yield was relatively higher in admitted patients than in OPD patients. In addition, BAL should be done more early in the admitted patients with malignancy, stem cell and/or organ transplantation and collagen vascular disease especially when they showed poor response to initial medications.

The usefulness of prophylactic use of acetazolamide in subjects with acute mountain sickness.

BACKGROUND: The mechanisms of acetazolamide (ACZ) in the prophylaxis of acute mountain sickness (AMS) remain unclear. This study evaluated the changes in physiological variables of sleep and heart rate variability (HRV) in subjects with earlier history of AMS who underwent prophylactic treatment of ACZ. METHODS: Nonacclimatized healthy subjects were transported using a bus from 555 m to 3150 m within 3 hours. Polysomnography (PSG) was performed 3 days before ascent (T0), for two consecutive nights at 3150 m (T1 and T2), and 2 days after descent (T3). HRV was measured before sleep and after awakening from T0 to T3. AMS was diagnosed using a self-reported Lake Louise score questionnaire. Subjects found confirmed to have AMS were enrolled in this study. The physiological variables and HRV were compared in AMS subjects without (control group) and with prophylactic ACZ (prophylactic ACZ group). RESULTS: Thirteen AMS subjects were enrolled. The PSG results were analyzed in eight and HRV were analyzed in nine of the 13 subjects. The prophylactic use of ACZ in the subjects with a history of AMS significantly improved sleep efficiency (p = 0.012) and awakening percentages (p = 0.017) at T1, significantly higher levels of arterial oxygen saturation (SaO2) and lower values of partial pressure end-tidal carbon dioxide tension (PETCO2) at four time points. Furthermore, they had a higher rapid eye movement sleep percentage (p = 0.05) at T2. Prophylactic ACZ treatment significantly increased the normalized unit of high frequency at T1 after awakening (p = 0.028). CONCLUSION: Significantly higher quality of sleep, higher SaO2 during sleep, and lower PETCO2 at high altitude were found in the subjects with a history of AMS using prophylactic ACZ before rapid ascent. ACZ may accelerate the acclimatization process for rapid ascents to high altitudes by increasing parasympathetic tone based on HRV analyses.

Effects of rapid ascent on the heart rate variability of individuals with and without acute mountain sickness.

PURPOSE: Through time- and frequency-domain analysis, we compared the effects of acute hypobaric hypoxia on the changes in heart rate variability (HRV) following night sleeping and morning awakening in individuals with and without acute mountain sickness (AMS). METHOD: Thirty-nine nonacclimatised healthy individuals were transported by bus from sea level to 3150 m within 3 h. Short-term HRV was measured two times a day-before sleeping (BS) and after awakening (AA)- at 3 days before ascent (T0), two consecutive nights at 3150 m (T1 and T2), and 2 days after descent (T3). AMS was diagnosed using the self-reported Lake Louise score questionnaire. RESULT: AMS developed in 19 of 39 participants (48.7%). At sea level, individuals had higher HRV at AA than at BS, and the trend of increased HRV at AA remained unchanged at high altitude, irrespective of AMS. At T1 BS, low-frequency power in normalised unit was significantly lower in participants with AMS than in those without AMS. Compared with those at T1 BS, the square root of the mean squared differences of successive normal-normal (NN) intervals, the number of interval differences of successive NN intervals more than 50 ms (NN50), and the proportion derived by dividing NN50 by the total number of NN intervals at T1 AA significantly increased in participants without AMS but nonsignificantly decreased in those with AMS. CONCLUSION: After rapid ascent, individuals with AMS did not demonstrate sympathetic hyperactivity but did exhibit withdrawal of cardiac vagal modulation in the morning following the first night's sleep.

Clinical Usefulness of Urinary Fatty Acid Binding Proteins in Assessing the Severity and Predicting Treatment Response of Pneumonia in Critically Ill Patients: A Cross-Sectional Study.

To investigate the clinical relevance of urinary fatty acid binding proteins (FABPs), including intestinal-FABP, adipocyte-FABP, liver-FABP, and heart-FABP in pneumonia patients required admission to respiratory intensive care unit (RICU).Consecutive pneumonia patients who admitted to RICU from September 2013 to October 2014 were enrolled except for those with pneumonia for more than 24 h before admission to RICU. Pneumonia patients were further divided into with and without septic shock subgroups. Twelve patients without infection were enrolled to serve as control group. Urine samples were collected on days 1 and 7 after admission to RICU for measuring FABPs and inflammatory cytokines. Clinical and laboratory data were collected and compared between pneumonia and control groups, and between the pneumonia patients with and without septic shock.There were no significant differences in urinary levels of various FABPs and inflammatory cytokines measured on day 1 between control and pneumonia groups. Urinary values of intestine-FABP (P = 0.020), adipocyte-FABP (P = 0.005), heart-FABP (P = 0.025), and interleukin-6 (P = 0.019) were significantly higher and arterial oxygen tension/fraction of inspired oxygen (PaO2/FiO2, P/F) ratio (P = 0.024) was significantly lower in pneumonia patients with septic shock on day 1 than in those without septic shock. After multivariate analysis, adipocyte-FABP was the independent factor (P = 0.026). Urinary levels of FABPs measured on day 7 of pneumonia patients were significantly lower in the improved than in nonimproved groups (P = 0.030 for intestine-FABP, P = 0.003 for adipocyte-FABP, P = 0.010 for heart-FABP, and P = 0.008 for liver-FABP, respectively). After multivariate analysis, adipocyte-FABP was the independent factor (P = 0.023).For pneumonia patients required admission to RICU, urinary levels of adipocyte-FABP on days 1 and 7 after admission to RICU may be valuable in assessing the pneumonia severity and in predicting treatment response, respectively. Further studies with larger populations are needed to verify these issues.

Clinical Usefulness of HRCT in Assessing the Severity of Pneumocystis jirovecii Pneumonia: A Cross-sectional Study.

The aim of this study was to investigate the clinical relevance of thoracic high-resolution computed tomography (HRCT) in evaluating the severity and outcome of Pneumocystis jirovecii pneumonia (PJP) in non-AIDS immunocompromised patients.We measured mean lung attenuation (MLA) and extent of increased attenuation (EIA) of PJP lesions on thoracic HRCT in 40 non-AIDS immunocompromised patients with PJP diagnosed by demonstration of the pathogens in cytological smears of bronchoalveolar lavage fluid. The MLA and EIA of PJP lesions on thoracic HRCT were used to investigate the severity of PJP. Clinically, the severity of PJP was determined by arterial oxygen tension/fraction of inspired oxygen concentration (PaO2/FiO2) ratio, acute physiology and chronic health evaluation (APACHE) II scores, the need of mechanical ventilation, and death.MLA highly correlated with EIA of PJP lesions (ρ = 0.906, P < 0.001). MLA and EIA of PJP lesions significantly correlated with PaO2/FiO2 (ρ = -0.481 and -0.370, respectively and P = 0.007 and 0.044, respectively). When intensive care unit (ICU) admission and HRCT performed were within 2 days, MLA and EIA of PJP lesions were significantly correlated with APACHE II score (ρ = 0.791 and 0.670, respectively and P = 0.001 and 0.009, respectively). There were significant differences in the values of MLA and EIA of PJP lesions between patients with and without assisted mechanical ventilator (MLA, median and [interquartile range, IQR, 25%, 75%] -516.44 [-572.10, -375.34] vs -649.27 [-715.62, -594.01], P < 0.001 and EIA, median and [IQR 25%, 75%] 0.75 [0.66, 0.82] vs 0.53 [0.45, 0.68], P = 0.003, respectively). The data of MLA and EIA of PJP lesions had limited value in identifying survivors and non-survivors.The MLA and EIA values of PJP lesions measured on thoracic HRCT might be valuable in assessing the severity of PJP in non-AIDS immunocompromised patients, but might have limited value in predicting the mortality of the patients.

Impact of rapid ascent to high altitude on sleep.

PURPOSE: Sleep disturbance at high altitude is common in climbers. In this study, we intended to evaluate the effect of rapid ascent on sleep architecture using polysomnography (PSG) and to compare the differences between subjects with and without acute mountain sickness (AMS). METHODS: The study included 40 non-acclimatized healthy subjects completing PSG at four time points, 3 days before the ascent (T0), two successive nights at 3150 m (T1 and T2), and 2 days after the descent (T3). All subjects were transported by bus from 555 to 3150 m within 3 h. AMS was diagnosed using self-reported questionnaire of Lake Louise score. RESULTS: Twenty of 40 (50%) subjects developed AMS. At high altitude, awakening percentages increased in AMS group but changed insignificantly in non-AMS group. Arousal index and apnea/hypopnea index (AHI) increased irrespective of AMS. The increases of AHI were more evident in non-AMS group than in AMS group. Compared to subjects without AMS, those with AMS had significantly lower sleep efficiency, lower central apnea index, and longer latencies to sleep and rapid eye movement (REM) sleep at T1 and lower REM sleep percentages at T1 and T2. Subjects with older age and lower minimum arterial oxygen saturation during sleep at sea level were prone to develop AMS. CONCLUSIONS: Higher AHI did not cause more frequent awakenings and arousals at high altitude. Central sleep apneas were observed in non-AMS but not in AMS group. Subjects unacclimatized to acute hypobaric hypoxia might have delayed and less REM sleep.

The impact of concomitant pulmonary infection on immune dysregulation in Pneumocystis jirovecii pneumonia.

BACKGROUND: Concurrent infection may be found in Pneumocystis jirovecii pneumonia (PJP) of non-acquired immunodeficiency syndrome (AIDS) patients, however, its impact on immune dysregulation of PJP in non-AIDS patients remains unknown. METHODS: We measured pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-8, IL-17, monocyte chemoattractant protein-1 (MCP-1) and anti-inflammatory cytokines including IL-10 and transforming growth factor (TGF)-ß1 and IL-1 receptor antagonist (IL-1RA) and inflammatory markers including high mobility group box 1, Krebs von den Lungen-6, receptor for advanced glycation end product, advanced glycation end product, surfactant protein D in bronchoalveolar lavage fluid (BALF) and blood in 47 pure PcP and 18 mixed PJP and other pulmonary infections (mixed PJP) in non-AIDS immunocompromised patients and explored their clinical relevance. The burden of Pneumocystis jirovecii in the lung was determined by counting number of clusters of Pneumocystis jirovecii per slide and the concentration of ß-D-glucan in BALF. PJP severity was determined by arterial oxygen tension/fraction of inspired oxygen concentration ratio, the need of mechanical ventilation and death. RESULTS: Compared with pure PJP group, mixed PJP group had significantly higher BALF levels of IL-1ß, TNF-α and IL-8 and significantly higher blood levels of IL-8. The BALF ratios of TNF-α/IL-10, IL-8/IL-10, IL-1ß/IL-10, TNF-α/TGF-ß1, IL-8/TGF-ß1, IL-1ß/TGF-ß1 and IL-1ß/IL-1RA were significantly higher in mixed than in pure PJP patients. There was no significant difference in clinical features and outcome between pure and mixed PJP groups, including inflammatory biomarkers and the fungal burden. In pure PJP patients, significantly higher BALF levels of IL-8 and the ratios of IL-8/IL-10, IL-1ß/TGF-ß1, MCP-1/TGF-ß1, MCP-1/IL1RA and IL-8/TGF-ß1 were found in the patients requiring mechanical ventilation and in non-survivors. CONCLUSIONS: In summary, concurrent pulmonary infection might enhance immune dysregulation of PJP in non-AIDS immunocompromised patients, but did not affect the outcome as evidenced by morbidity and mortality. Because of limited number of cases studied, further studies with larger populations are needed to verify these issues.

The importance of pro-inflammatory and anti-inflammatory cytokines in Pneumocystis jirovecii pneumonia.

The role of pro-inflammatory and anti-inflammatory cytokines in Pneumocystis jirovecii pneumonia (PcP) of non-AIDS immunocompromised patients remains unclear. We measured the levels of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and anti-inflammatory cytokines including IL-10 and transforming growth factor (TGF)-ß1 in bronchoalveolar lavage fluid (BALF) and blood in 36 non-AIDS immunocompromised patients with PcP diagnosed by BAL and explored their clinical importance. The severity of PcP was determined by arterial oxygen tension/fraction of inspired oxygen concentration (PaO2/FiO2) ratio, the need of mechanical ventilation and the death. Twenty-five subjects without evidence of lung abnormality were included as control group. Compared with control group, PcP patients had significantly higher BALF levels of IL-1ß, TNF-α, IL-6, IL-8 and MCP-1 and significantly higher blood levels of IL-10, TGF-ß1, IL-8, IL-6 and MCP-1. For PcP patients, BALF levels of IL-8, IL-8/IL-10 ratio and IL-8/TGF-ß1 ratio and blood levels of IL-8 and IL-8/IL-10 ratio were significantly higher in the patients with PaO2/FiO2 < 200 mmHg than in those with PaO2/FiO2 > 200 mmHg. Similarly, significantly higher BALF levels of IL-8, IL-8/IL-10 ratio, IL-1ß/IL-10, IL-1ß/TGF-ß1 ratio, MCP-1/TGF-ß1 ratio and IL-8/TGF-ß1 ratio were found in the patients requiring mechanical ventilation and in non-survivors. In summary, an imbalance of pro-inflammatory and anti-inflammatory cytokines in BALF was found in PcP of non-AIDS immunocompromised patients. BALF levels of IL-8, IL-8/IL-10 ratio, IL-1ß/IL-10 ratio, IL-1ß/TGF-ß1 ratio, MCP-1/TGF-ß1 ratio and IL-8/TGF-ß1 ratio may be of value in assessing the severity of PcP and in predicting the outcome of the patients.

Statin-induced lung injury: diagnostic clue and outcome.

BACKGROUND: Statin-induced lung injury (SILI) is an uncommon but serious complication of statins. The clinical features and outcome of patients with SILI vary widely. Clinical data relevant to diagnosis and outcome of patients with SILI were investigated in this study. METHOD: Four cases of SILI diagnosed at our institute and 12 cases reported in the English literature from 1995 to 2010 were studied. The patients were further divided into favourable and unfavourable outcome groups and compared. RESULTS: Compared with the 12 previously reported cases, fever (p=0.008) and consolidation (p=0.027) were more common and duration of statin treatment was significantly shorter (p=0.030) in our patients. Foamy alveolar macrophages in bronchoalveolar lavage fluid (BALF) were found in our four patients. Patients with cough (p=0.024), fever (p=0.026) and alveolar infiltrates (p=0.036), especially ground-glass opacity (GGO) (p=0.001) shown on thoracic high-resolution CT (HRCT), had a favourable outcome. Conversely, those with fibrosis shown on HRCT (p=0.008) had an unfavourable outcome. Stepwise logistic regression analysis demonstrated that cough (p=0.011), fever (p=0.005), and alveolar infiltrates (p=0.017), GGO (p<0.001) and fibrosis (p=0.002) shown on thoracic HRCT were independent factors affecting the outcome of SILI. CONCLUSIONS: For patients with SILI, pulmonary phospholipidosis, as shown by foamy alveolar macrophages in BALF, may be valuable in diagnosis, and clinical symptoms and thoracic HRCT findings are of value in predicting the outcome.

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)-1ß, 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.