Fang-Chi Lin

Impact of rapid ascent to high altitude on sleep

PurposeSleep 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).MethodsThe study included 40 non-acclimatized healthy subjects completing PSG at four time points, 3xa0days before the ascent (T0), two successive nights at 3150xa0m (T1 and T2), and 2xa0days after the descent (T3). All subjects were transported by bus from 555 to 3150xa0m within 3xa0h. AMS was diagnosed using self-reported questionnaire of Lake Louise score.ResultsTwenty 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.ConclusionsHigher 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 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)-1β, IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and anti-inflammatory cytokines including IL-10 and transforming growth factor (TGF)-β1 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-1β, TNF-α, IL-6, IL-8 and MCP-1 and significantly higher blood levels of IL-10, TGF-β1, IL-8, IL-6 and MCP-1. For PcP patients, BALF levels of IL-8, IL-8/IL-10 ratio and IL-8/TGF-β1 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-1β/IL-10, IL-1β/TGF-β1 ratio, MCP-1/TGF-β1 ratio and IL-8/TGF-β1 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-1β/IL-10 ratio, IL-1β/TGF-β1 ratio, MCP-1/TGF-β1 ratio and IL-8/TGF-β1 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 impact of concomitant pulmonary infection on immune dysregulation in Pneumocystis jirovecii pneumonia

BackgroundConcurrent 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.MethodsWe measured pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, IL-17, monocyte chemoattractant protein-1 (MCP-1) and anti-inflammatory cytokines including IL-10 and transforming growth factor (TGF)-β1 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 β-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.ResultsCompared with pure PJP group, mixed PJP group had significantly higher BALF levels of IL-1β, 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-1β/IL-10, TNF-α/TGF-β1, IL-8/TGF-β1, IL-1β/TGF-β1 and IL-1β/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-1β/TGF-β1, MCP-1/TGF-β1, MCP-1/IL1RA and IL-8/TGF-β1 were found in the patients requiring mechanical ventilation and in non-survivors.ConclusionsIn 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 role of total bile acid in oral secretions in ventilator-associated pneumonia ☆,☆☆

PURPOSEnThe 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).nnnMATERIALSnThis 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.nnnRESULTSnThirty-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.nnnCONCLUSIONSnDuodenogastroesophageal 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.

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

AbstractThe 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 (&rgr;u200a=u200a0.906, Pu200a<u200a0.001). MLA and EIA of PJP lesions significantly correlated with PaO2/FiO2 (&rgr;u200a=u200a−0.481 and −0.370, respectively and Pu200a=u200a0.007 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 (&rgr;u200a=u200a0.791 and 0.670, respectively and Pu200a=u200a0.001 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], Pu200a<u200a0.001 and EIA, median and [IQR 25%, 75%] 0.75 [0.66, 0.82] vs 0.53 [0.45, 0.68], Pu200a=u200a0.003, 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.

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

PurposeThrough 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).MethodThirty-nine nonacclimatised healthy individuals were transported by bus from sea level to 3150xa0m within 3xa0h. 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 3150xa0m (T1 and T2), and 2 days after descent (T3). AMS was diagnosed using the self-reported Lake Louise score questionnaire.ResultAMS 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 50xa0ms (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.ConclusionAfter 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.