Increased di-(2-ethylhexyl) phthalate exposure poses a differential risk for adult asthma clusters.

BACKGROUND: DEHP, a common plasticizer known for its hormone-disrupting properties, has been associated with asthma. However, a significant proportion of adult asthma cases are "non-atopic", lacking a clear etiology. METHODS: In a case-control study conducted between 2011 and 2015, 365 individuals with current asthma and 235 healthy controls from Kaohsiung City were enrolled. The control group comprised individuals without asthma, Type 2 Diabetes Mellitus (T2DM), hypertension, or other respiratory/allergic conditions. The study leveraged asthma clusters (Clusters A to F) established in a prior investigation. Analysis involved the examination of urinary DEHP metabolites (MEHP and MEHHP), along with the assessment of oxidative stress, sphingolipid metabolites, and inflammatory biomarkers. Statistical analyses encompassed Spearman's rank correlation coefficients, multiple logistic regression, and multinomial logistic regression. RESULTS: Asthma clusters (E, D, C, F, A) exhibited significantly higher ORs of MEHHP exposures compared to the control group. When considering asthma-related comorbidities (T2DM, hypertension, or both), patients without comorbidities demonstrated significantly higher ORs of the sum of primary and secondary metabolites (MEHP + MEHHP) and MEHHP compared to those with asthma comorbidities. A consistent positive correlation between urinary HEL and DEHP metabolites was observed, but a consistent negative correlation between DEHP metabolites and selected cytokines was identified. CONCLUSION: The current study reveals a heightened risk of MEHHP and MEHP + MEHHP exposure in specific asthma subgroups, emphasizing its complex relationship with asthma. The observed negative correlation with cytokines suggests a new avenue for research, warranting robust evidence from epidemiological and animal studies.

Environmental risks and sphingolipid signatures in adult asthma and its phenotypic clusters: a multicentre study.

BACKGROUND: Adult asthma is phenotypically heterogeneous with unclear aetiology. We aimed to evaluate the potential contribution of environmental exposure and its ensuing response to asthma and its heterogeneity. METHODS: Environmental risk was evaluated by assessing the records of National Health Insurance Research Database (NHIRD) and residence-based air pollution (particulate matter with diameter less than 2.5 micrometers (PM2.5) and PM2.5-bound polycyclic aromatic hydrocarbons (PAHs)), integrating biomonitoring analysis of environmental pollutants, inflammatory markers and sphingolipid metabolites in case-control populations with mass spectrometry and ELISA. Phenotypic clustering was evaluated by t-distributed stochastic neighbor embedding (t-SNE) integrating 18 clinical and demographic variables. FINDINGS: In the NHIRD dataset, modest increase in the relative risk with time-lag effect for emergency (N=209 837) and outpatient visits (N=638 538) was observed with increasing levels of PM2.5 and PAHs. Biomonitoring analysis revealed a panel of metals and organic pollutants, particularly metal Ni and PAH, posing a significant risk for current asthma (ORs=1.28-3.48) and its severity, correlating with the level of oxidative stress markers, notably Nε-(hexanoyl)-lysine (r=0.108-0.311, p<0.05), but not with the accumulated levels of PM2.5 exposure. Further, levels of circulating sphingosine-1-phosphate and ceramide-1-phosphate were found to discriminate asthma (p<0.001 and p<0.05, respectively), correlating with the levels of PAH (r=0.196, p<0.01) and metal exposure (r=0.202-0.323, p<0.05), respectively, and both correlating with circulating inflammatory markers (r=0.186-0.427, p<0.01). Analysis of six phenotypic clusters and those cases with comorbid type 2 diabetes mellitus (T2DM) revealed cluster-selective environmental risks and biosignatures. INTERPRETATION: These results suggest the potential contribution of environmental factors from multiple sources, their ensuing oxidative stress and sphingolipid remodeling to adult asthma and its phenotypic heterogeneity.

Functional polymorphisms of the TLR7 and TLR8 genes contribute to Mycobacterium tuberculosis infection.

Tuberculosis (TB) has recently re-emerged as a major global public health threat and Mycobacterium tuberculosis (MTB) is a highly successful pathogen that evolved remarkable strategies to establish persistent infection. There is strong evidence that host genetic factors influence individual susceptibility to TB. In this study, we evaluated the associations between the TLR7 and TLR8 genetic polymorphisms and TB susceptibility in Chinese individuals. The results demonstrated that the frequency of the TLR8-129C allele was higher in male patients with pulmonary TB than in healthy controls (22.9% vs. 6.8%, p < 0.001). Based on haplotype analysis, the frequency of the TLR7 IVS2-151A/TLR8 -129C haplotype increased the risk for TB infection compared to the wild-type allele (TLR7 IVS2-151A/TLR8 -129G), with OR = 3.23 (95% CI = 1.58-6.61; p = 0.001). An ex vivo phagocytosis assay that examined the functional effects of these polymorphisms on the defense against MTB revealed higher phagocytosis in monocytes from males with the TLR7 IVS2-151A/TLR8 -129C genotype than in those with the wild-type allele (73.0 ± 20.3% versus 34.6 ± 8.1%; p = 0.03). In addition, mRNA expression and cytokine production were analyzed in the whole blood of male healthy volunteers stimulated with inactivated MTB ex vivo. TNFα production was lower in TLR7 IVS2-151A/TLR8 -129C subjects than in those with the wild-type allele (578.4 ± 90.3 pg/ml versus 1043 ± 136 pg/ml; p = 0.03), and the expression of TLR7 was significantly impaired (0.8 ± 0.1 folds, p = 0.05) after MTB stimulation. In conclusion, these findings provide evidence that TLR7 and TLR8 genetic polymorphisms are associated with susceptibility to MTB infection, and the link is shaped by less effective MTB phagocytosis and impaired TLR signaling.

Comparison of the safety and efficacy of a fixed-dose combination regimen and separate formulations for pulmonary tuberculosis treatment.

OBJECTIVES: Fixed-dose combination formulations, which simplify the administration of drugs and prevent the development of drug resistance, have been recommended as a standard anti-tuberculosis treatment regimen. However, the composition and dosage recommendations for fixed-dose combination formulations differ from those for separate formulations. Thus, questions about the effectiveness and side effects of combination formulations remain. The aim of this study was to compare the safety and efficacy of these two types of anti-tuberculosis regimens for pulmonary tuberculosis treatment. METHOD: A prospective, randomized controlled study was conducted using the directly observed treatment short-course strategy. Patients were randomly allocated to one of two short-course regimens. One year after completing the treatment, these patients' outcomes were analyzed. ClinicalTrials.gov: NCT00979290. RESULTS: A total of 161 patients were enrolled, 142 of whom were evaluable for safety assessment. The two regimens had a similar incidence of adverse effects. In the per-protocol population, serum bilirubin concentrations at the peak level, at week 4, and at week 8 were significantly higher for the fixed-dose combination formulation than for the separate formulations. All patients had negative sputum cultures at the end of the treatment, and no relapse occurred after one year of follow-up. CONCLUSIONS: In this randomized study, transient higher serum bilirubin levels were noted for the fixed-dose combination regimen compared with the separate formulations during treatment. However, no significant difference in safety or efficacy was found between the groups when the directly observed treatment short-course strategy was used.

Comparison of the safety and efficacy of a fixed-dose combination regimen and separate formulations for pulmonary tuberculosis treatment

OBJECTIVES: Fixed-dose combination formulations, which simplify the administration of drugs and prevent the development of drug resistance, have been recommended as a standard anti-tuberculosis treatment regimen. However, the composition and dosage recommendations for fixed-dose combination formulations differ from those for separate formulations. Thus, questions about the effectiveness and side effects of combination formulations remain. The aim of this study was to compare the safety and efficacy of these two types of anti-tuberculosis regimens for pulmonary tuberculosis treatment. METHOD: A prospective, randomized controlled study was conducted using the directly observed treatment short-course strategy. Patients were randomly allocated to one of two short-course regimens. One year after completing the treatment, these patients’ outcomes were analyzed. ClinicalTrials.gov: NCT00979290. RESULTS: A total of 161 patients were enrolled, 142 of whom were evaluable for safety assessment. The two regimens had a similar incidence of adverse effects. In the per-protocol population, serum bilirubin concentrations at the peak level, at week 4, and at week 8 were significantly higher for the fixed-dose combination formulation than for the separate formulations. All patients had negative sputum cultures at the end of the treatment, and no relapse occurred after one year of follow-up. CONCLUSIONS: In this randomized study, transient higher serum bilirubin levels were noted for the fixed-dose combination regimen compared with the separate formulations during treatment. However, no significant difference in safety or efficacy was found between the groups when the directly observed treatment short-course strategy was used. .

Physical activity preferences among patients with lung cancer in Taiwan.

BACKGROUND: Lung cancer is the leading cause of cancer deaths in the world. Physical activity could help lung cancer patients improve their health. OBJECTIVE: The purpose of our study was to investigate lung cancer patients' physical activity preferences and relevant contributing factors, so that we could develop individualized intervention strategies to fit their needs. METHODS: This study used a descriptive and correlational design. Instruments included a physical activity preference survey form, the Physical Activity Social Support Scale, and Physical Activity Self-efficacy Scale. RESULTS: From 81 lung cancer patients' physical activity preferences, our results showed that during the course of their illness, 85.2% of patients wanted to have a physical activity consultation and preferred to obtain advice from their physicians (28.4%) through face-to-face counseling (48.1%). Moreover, patients (70.4%) showed an interest in physical activity programs, and many (69.1%) revealed that they were able to participate. About 88.9% of patients showed a preference for walking, and 54.3% patients preferred moderate physical activity. CONCLUSIONS: This study also revealed that social support and self-efficacy for physical activity effectively predicted moderate physical activity preferences. IMPLICATIONS FOR PRACTICE: The adherence to regular physical activity is improved by understanding the lung cancer patients' unique preferences for physical activity.

Trend analysis of hospital resource utilization for prolonged mechanical ventilation patients in Taiwan: a population-based study.

BACKGROUND: The aging Taiwan population is expected to require vast medical resources, including prolonged mechanical ventilation (PMV). This study determined the trends in hospital resource utilization and associated factors in PMV patients in Taiwan. METHODS: All patients who had received mechanical ventilation for > 21 days (International Classification of Diseases, 9th Revision, Clinical Modification codes 518.81-518.89) during 2004-2007 were recruited to the study. Administrative claims data obtained from the Bureau of National Health Insurance of Taiwan were analyzed. RESULTS: The study analyzed 65,181 patients who had received PMV during 2004-2007. The number of PMVs per 100,000 persons was 94.30 in 2004, and it gradually decreased to 89.38 in 2007, which was a change rate of -5.22%. During the study period, stay significantly decreased, from 35.12 days to 31.61 days, whereas hospital treatment costs significantly increased, from $7,933.17 to $8,257.52 (P < .001). Considerably decreased stay and increased hospital treatment costs were significantly associated with age, number of comorbidities, hospital level, hospital volume, and patient referral source (P < .001). CONCLUSIONS: These population-based data demonstrated a decrease in the prevalence of PMV, especially for older patients, and that stay decreased; however, hospital treatment costs increased. Moreover, healthcare providers and patients should recognize that attributes of both the patient and the hospital may affect hospital resource utilization. Additionally, these analytical results should be applicable to similar populations in other countries.

Successful treatment of septic shock and respiratory failure due to leptospirosis and scrub typhus coinfection with penicillin, levofloxacin, and activated protein C.

Leptospirosis and scrub typhus are common zoonoses and coinfection with both diseases has been reported sporadically, particularly in tropical and subtropical areas. A 53-year-old male presented with acute hypoxemic respiratory failure and septic shock due to leptospirosis and scrub typhus coinfection confirmed by serological assessments. Antibiotics, including intravenous penicillin and levofloxacin, were administered and human recombinant activated protein C was added because of a high risk of death due to septic shock with multiple organ failure. The patient's hemodynamics and hypoxemia substantially improved 4 days later and he had a complete recovery from the disease after 10 days of hospitalization. Coinfection of leptospirosis and scrub typhus may easily go unrecognized by physicians in febrile travelers or patients in the region where both diseases are endemic. In severe and critical cases of leptospirosis, scrub typhus, or coinfection with both, the use of APC in addition to appropriate antibiotic treatment and standard critical care might provide a greater chance for survival and a favorable outcome.

Gefitinib as first-line therapy for advanced or metastatic non-small cell lung cancer patients in southern Taiwan.

Gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, is effective in treating patients with non-small cell lung cancer (NSCLC) after unsuccessful chemotherapy. However, survival outcomes and predictors for its effectiveness in chemotherapy-naive NSCLC patients are still not clear. The goal of this study was to investigate the response and survival rates and identify the predictive factors for patients with advanced or metastatic disease receiving gefitinib as first-line therapy. We retrospectively analyzed the response and survival rates of patients with advanced or metastatic NSCLC who had received gefitinib as first-line therapy across six medical institutes in Southern Taiwan between May 2004 and April 2006. The relationship between the response and survival rates to the known predictive factors for gefitinib response and survival was also investigated. A total of 97 patients (65 females and 32 males) were enrolled in this study. Seventy-four patients (76%) had never smoked. Eighty-eight patients (91%) had adenocarcinoma or bronchioloalveolar cell carcinoma. The objective response rate was 56% and the disease control rate (partial response plus stable disease) was 76%. Only poor performance status (Eastern Cooperative Oncology Group score, 3-4) was statistically significantly associated with overall response in this study. The 1-year survival rate was 77%. We suggest that first-line gefitinib monotherapy is promising in some subgroups of Asian patients with NSCLC. Further randomized controlled studies are needed to validate the effectiveness of first-line gefitinib therapy.

Performance evaluation and enhancement of lung sound recognition system in two real noisy environments.

This study investigates the problems associated with lung sound recognition under noisy conditions. Firstly, the effects of noise on the lung sound feature representation and the classification performance are analyzed. Two kinds of feature representations, autoregressive and mel-frequency cepstral coefficients, are used to characterize the lung sound signals. Dynamic time warping is used to categorize the lung sounds to one of the three: normal, wheezes, or crackles. Our experimental results indicate that additive noise produces a mismatch between training and recognition environments and deteriorates the classification performance with a decrease in the SNR levels. In order to compensate the degrading effect of noise on the lung sound recognition, a dual sensor spectral subtraction algorithm is applied to the lung sound signals before the extraction of lung sound features. It is observed that the proposed algorithm is capable of providing adequate performance in terms of noise suppression and lung sound signal enhancement.

Hoarseness as a first manifestation of aortotracheal fistula.

Aortotracheal fistula is uncommon but invariably fatal if not diagnosed early and accurately. Most fistulas are related to aneurysm of the thoracic aorta. Massive hemoptysis is reported to occur in more than half of the patients and is often the final event. We report a patient with hoarseness as an initial manifestation due to the painless formation of a pseudoaneurysm of aortic arch, which soon ruptured. Bronchoscopy disclosed a tracheal bulging mass with surface irregularity on the distal end of trachea before massive hemoptysis. We thought, faced with the cardiovocal syndrome accompanied with hemoptysis, lethal aortopulmonary fistula should be highly suspected.

Monitoring treatment responses in patients with pulmonary TB using serial lung gallium-67 scintigraphy.

OBJECTIVE: Gallium-67 scintigraphy is more sensitive than chest radiography in a single concurrent detection of pulmonary tuberculosis (TB). As for inflammation, the intensity of pulmonary uptake of 67Ga citrate theoretically is a function of the inflammation level in the lung. To maximize clinical applicability of 67Ga scintigraphy in the evaluation of pulmonary TB, we prospectively assessed serial qualitative associations between intensity of the uptake of 67Ga citrate and the severity of lung inflammation, reflected by the burden of Mycobacterium tuberculosis in the sputum of patients undergoing anti-TB chemotherapy. SUBJECTS AND METHODS: Each enrolled patient had chest radiographic, microbiologic, 67Ga imaging, and semiquantitation of sputum acid-fast bacillus (AFB) assessments before and at the third and sixth months after receiving anti-TB chemotherapy. The burden of pulmonary M. tuberculosis (presumably, in proportion to the semiquantitation of AFB in sputum) and the intensity of 67Ga citrate uptake in the lung at each synchronized assessment were regarded as a paired variable. Odds ratios were obtained from odds (derived using generalized estimating equations) in favor of higher pulmonary 67Ga uptake in differing scores of semiquantitation of sputum AFB. Linear trend for pulmonary 67Ga citrate uptake corresponding to varied pulmonary M. tuberculosis burdens was assessed using contrast analysis of their odds ratios. RESULTS: Thirty patients (24 men and six women) with pulmonary TB were enrolled. Eighty-six paired semiquantitations of sputum AFB-67Ga-scintigraphic studies were collected. Twenty-six patients were cured of their pulmonary TB. The pulmonary 67Ga uptake increased in proportion to the higher score of semiquantitation of sputum AFB (p = 0.009, for trend). CONCLUSION: In patients with pulmonary TB, the higher the burden of M. tuberculosis in the lung, the higher the intensity of pulmonary 67Ga citrate uptake. Serial 67Ga-scintigraphy examinations are helpful in evaluations of the effectiveness of anti-TB therapy when assessments based on chest radiography are difficult.

Sarcoidosis in southern Taiwan.

PURPOSE: To investigate the disease characteristics of sarcoidosis in southern Taiwan, and to investigate diagnostic methods. METHODS: We retrospectively reviewed the medical records of all patients diagnosed with sarcoidosis at Chang Gung Memorial Hospital, Kaohsiung, from March 1988 to February 2002. RESULTS: A total of 12 patients (3 men, 9 women), with a mean age of 44.5 years, and a diagnosis of sarcoidosis by positive histology and either a typical chest roentgenogram or clinical presentation were included. All 12 patients had intrathoracic involvement (hilar or mediastinal lymph nodes, 12; lungs, 5), eight had skin involvement, and two had extrathoracic lymph node involvement. The most frequent biopsy specimens were from the skin (n = 10), followed by the intrathoracic lymph nodes (n = 4), lungs (n = 2), and extrathoracic lymph nodes (n = 2). Four patients had positive biopsies from two organs. Our data showed an older age distribution and a greater female predominance of the disease compared with Western countries. A higher rate of intrathoracic and skin involvement was also found, but the reason for this was not clear. CONCLUSIONS: Greater awareness of possible skin involvement may enable chest physicians and clinical practitioners to suspect this condition earlier. A histologic diagnosis from skin biopsy should then be made, rather than using more invasive procedures.