Deep Learning-Based Classification and Semantic Segmentation of Lung Tuberculosis Lesions in Chest X-ray Images.

We present a deep learning (DL) network-based approach for detecting and semantically segmenting two specific types of tuberculosis (TB) lesions in chest X-ray (CXR) images. In the proposed method, we use a basic U-Net model and its enhanced versions to detect, classify, and segment TB lesions in CXR images. The model architectures used in this study are U-Net, Attention U-Net, U-Net++, Attention U-Net++, and pyramid spatial pooling (PSP) Attention U-Net++, which are optimized and compared based on the test results of each model to find the best parameters. Finally, we use four ensemble approaches which combine the top five models to further improve lesion classification and segmentation results. In the training stage, we use data augmentation and preprocessing methods to increase the number and strength of lesion features in CXR images, respectively. Our dataset consists of 110 training, 14 validation, and 98 test images. The experimental results show that the proposed ensemble model achieves a maximum mean intersection-over-union (MIoU) of 0.70, a mean precision rate of 0.88, a mean recall rate of 0.75, a mean F1-score of 0.81, and an accuracy of 1.0, which are all better than those of only using a single-network model. The proposed method can be used by clinicians as a diagnostic tool assisting in the examination of TB lesions in CXR images.

Impact of active pulmonary tuberculosis on the prognosis of patients with upper aerodigestive cancers: An 8-year observational study in a nationwide cohort.

BACKGROUND AND OBJECTIVE: Tuberculosis (TB), a contagious disease with high morbidity and mortality, is prevalent among immunocompromised patients including those with cancers. We describe the risk subgroups and impact of active TB on the prognosis of patients with upper aerodigestive cancers. METHODS: We conducted a retrospective, nationwide cohort study from January 2009 to December 2014, and followed up until the end of 2016, using the database of the Taiwanese National Health Insurance (NHI) program. Patients newly diagnosed with oral, nasopharyngeal, laryngeal, and esophageal cancers were defined as the upper aerodigestive cancer cohort. Active pulmonary TB infection was identified as a time-dependent variable in the analysis of the risk subgroups and prognostic impact in our study cohort. RESULTS: A total of 57,543 patients were enrolled, and 890 patients (1.55 %) had active pulmonary TB during the follow-up period. The TB incidence was highest in patients with esophageal cancer and lowest in patients with nasopharyngeal cancer (1443 and 236 per 100, 000 person-years, respectively). Moreover, advanced cancer stage and inoperable cancer are considered risk factors for TB. Furthermore, patients with TB infection had a shorter survival (HR: 1.86, 95 % CI: 1.70-2.04), after matching cancer type, stage, and calendar year of diagnosis with patients without TB. CONCLUSION: Active pulmonary TB is prevalent in patients with upper aerodigestive cancers and is independently associated with an increased risk of death. Identifying the risk factors for TB in these cancer patients is important both for infectious disease control and outcome evaluation.

Functional Analysis of Genetic Variations in Surfactant Protein D in Mycobacterial Infection and Their Association With Tuberculosis.

Surfactant proteins (SPs)-A and -D are C-type lectins of the collectin family and function in the clearance of infectious particles in the lungs. Some polymorphisms of SPs that give rise to amino acid changes have been found to affect their function. Several SP-A gene polymorphisms have been reported to be associated with respiratory infection diseases, such as tuberculosis (TB). However, the relationship between surfactant proteins D (SP-D) polymorphisms and TB is still unclear. To study the associations between SP-D polymorphisms and TB, the correlations of SP-D polymorphisms with TB were examined in a case-control study, which included 364 patients with TB and 177 control subjects. In addition, we cloned two major SP-D exonic polymorphism C92T (rs721917) and A538G (rs2243639) constructs and used these for in vitro assays. The effects of SP-D polymorphisms on agglutination and other interactions with Mycobacterium bovis bacillus Calmette-Guérin (M. bovis BCG) were evaluated. In comparison with SP-D 92C (amino acid residue 16, Threonine), our results showed that SP-D 92T (amino acid residue 16, Methionine) had a lower binding ability to M. bovis BCG, a lower capacity to inhibit phagocytosis, lesser aggregation, poorer survival of bacillus Calmette-Guérin (BCG)-infected MH-S cells, and less inhibition of intracellular growth of M. bovis BCG. The case-control association study showed that the 92T homozygous genotype was a risk factor for TB. However, a lesser effect was seen for polymorphism A538G. In conclusion, the results of functional and genetic analyses of SP-D variants consistently showed that the SP-D 92T variant increased susceptibility to TB, which further confirmed the role of SP-D in pulmonary innate immunity against mycobacterial infection.

Prognostic effect of tuberculosis on patients with occupational lung diseases: A 13-year observational study in a nationwide cohort.

Occupational lung diseases are well recognized risk factors for tuberculosis (TB). However, little research investigated the effect of TB on the clinical course and outcome of occupational lung diseases.We conducted a 13-year observational study of a nationwide cohort to evaluate the risk and prognosis of TB among patients with occupational lung diseases in Taiwan.By using the Taiwan National Health Insurance database, occupational lung diseases cohort was identified according to diagnosis codes from 1998 to 2008 and prospectively monitored until the end of 2010, loss to follow-up, or death. Newly diagnosed TB, comorbidities, and demographic characteristics were evaluated as prognostic variables in the survival analysis of patients with occupational lung diseases using Cox proportional hazard regression models.A total of 12,787 study participants were enrolled with an average of 9.69 years of follow-up. Among them, 586 (4.58%) had newly diagnosed TB and 3180 (24.87%) died during follow-up. The incidence of TB was 473 per 100,000 person-years, and the risk of TB infection significantly increased over time. The independent risk factors for mortality included male gender (hazard ratio [HR]: 2.23, 95% confidence interval [CI]: 1.91-2.60), age (HR: 1.05, 95% CI: 1.05-1.06), TB (HR: 1.17, 95% CI: 1.01-1.37), congestive heart failure (HR: 1.44, 95% CI: 1.17-1.79), cerebrovascular disease (HR: 1.34, 95% CI: 1.15-1.57), chronic obstructive pulmonary disease (HR: 1.44, 95% CI: 1.33-1.56), and asthma (HR: 1.27, 95% CI: 1.15-1.40). In addition, patients with TB infections had worse outcomes in the survival analysis than those without TB (log-rank test P = 0.02).Despite the low prevalence of occupational lung diseases in Taiwan, patients with those diseases had a higher TB incidence than the general population did (473 vs 55 per 100,000 person-years). Furthermore, even with effective antimicrobial chemotherapy, TB infection was a prognostic factor leading to poor outcomes in the patients with occupational lung diseases. We recommend intensive medical surveillance of TB in these high-risk patients for better control of TB and improvement of occupational health in Taiwan.

Associated factors for tuberculosis recurrence in Taiwan: a nationwide nested case-control study from 1998 to 2010.

BACKGROUND: The contribution of human immunodeficiency virus (HIV) co-infection to tuberculosis (TB) recurrence is well established worldwide. We conducted this study to investigate associated factors for recurrent TB in Taiwan, which has a relatively low prevalence of HIV. METHODS: A case-control study nested within a nationwide population-based cohort was performed using the Taiwan National Health Insurance (NHI) database from 1998 to 2010. Patients with notified TB were identified according to diagnosis codes and prescriptions of anti-TB drugs for more than 60 days. Recurrent TB was defined as cases being retreated for more than 60 days and 6 months after the end of previous TB episode. Four controls were randomly selected from cohort and matched to each case by observational period within a calendar year. Socio-demographic variables and comorbidities were evaluated as factors associated with TB recurrence. RESULTS: There were totally 760 patients being investigated (608 controls and 152 cases). During an average 5.12 years of follow-up, 3.76% of all developed recurrent TB and the incidence of TB recurrence was 734 per 100,000 person-years. About half of recurrence (55%) was notified within three years of follow-up, and most (86%) recurrences were intrapulmonary. Independent associated factors for TB recurrence included: male (odds ratio, OR: 2.23, 95% confidence interval, CI: 1.40-3.53), diabetes mellitus (DM) (OR: 1.51, 95% CI: 1.02-2.13), chronic obstructive pulmonary disease (COPD) (OR: 1.59, 95% CI: 1.08-2.36) and lower socio-economic status (p=0.001 between groups). CONCLUSIONS: Despite low prevalence of HIV in the Taiwanese population, the incidence of recurrent TB among Taiwanese was not less than that of other countries. Identification of subgroups such as male gender, low economic status, DM and COPD should be a high priority in TB control programs.

Validation of the GOLD 2013 classification in predicting exacerbations and mortality in Taiwanese patients with chronic obstructive pulmonary disease.

BACKGROUND/PURPOSE: Evidence for the effectiveness of the new multidimensional GOLD (Global Initiative for Chronic Obstructive Lung Disease) classification is currently limited. The new classification has been validated in the United States and Europe, but validation in Asian patients is still lacking. We examined the abilities of the GOLD 2013 classification to predict clinical outcomes in Taiwanese patients with chronic obstructive pulmonary disease (COPD). METHODS: Patients with COPD were recruited from January 2006 to December 2012 and followed up for exacerbation and mortality. The predictive abilities of various assessments were compared through logistic regression analysis using receiver operating curve (ROC) estimations and area under the curve (AUC). RESULTS: A total of 471 patients with COPD were analyzed. The GOLD 2013 groups at high risk of exacerbation (C and D) experienced a higher average number of exacerbations per year (2.1 ± 3.1 vs. 0.3 ± 1.0, p < 0.001) than the low risk groups (A and B). The mortality rates were 10.1% in GOLD 2013 Group A, 14.1% in Group B, 4.0% in Group C, and 30.5% in Group D. The AUC values for GOLD 2013 and GOLD 2007 were 0.78 versus 0.67 (p < 0.001) for exacerbation, and 0.66 versus 0.61 (p = 0.15) for mortality. CONCLUSION: The GOLD 2013 classification has powerful ability to predict exacerbation, but poor ability to predict mortality. The prognostic validity of the GOLD 2013 classification to predict exacerbations was better than the GOLD 2007 classification.

Comparison of global initiative for chronic obstructive pulmonary disease 2013 classification and body mass index, airflow obstruction, dyspnea, and exacerbations index in predicting mortality and exacerbations in elderly adults with chronic obstructive pulmonary disease.

OBJECTIVES: To examine whether the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) 2013 revision offers greater predictive ability than the body mass index, airflow obstruction, dyspnea, and exacerbations (BODEx) index in elderly adults with chronic obstructive pulmonary disease (COPD). DESIGN: Prospective cohort study. SETTING: University-affiliated medical center. PARTICIPANTS: Taiwanese outpatients with COPD (N = 354). MEASUREMENTS: Participants were classified as Group A (low risk with mild dyspnea), Group B (low risk with more-severe dyspnea), Group C (high risk with mild dyspnea), and Group D (high risk with more-severe dyspnea) for GOLD 2013 and from Quartile 1 (0-2 points) to 4 (7-9 points) for BODEx score. Ability to predict exacerbations and mortality was compared using logistic regression analysis with receiver operating characteristic (ROC) curve estimations and area under the ROC curve (AUC). RESULTS: Mortality was 14.1% for GOLD Group A, 14.5% for Group B, 6.5% for Group C, and 35.8% for Group D and 15.2% for BODEx Quartile 1, 22.5% for Quartile 2, 28.1% for Quartile 3, and 79.2% for Quartile 4. Risk of exacerbation relative to Group A was 1.7 (95% confidence interval (CI) = 0.6-4.3) for Group B, 14.1 (95% CI = 4.6-43.2) for Group C, and 17.9 (95% CI = 7.6-42.0) for Group D. The AUC for the GOLD classification and BODEx index were 0.65 and 0.67 for mortality (P = .60) and 0.79 and 0.73 for exacerbation (P = .03). CONCLUSION: The GOLD 2013 classification performed well in identifying individuals at risk of exacerbations, and its predictive ability for exacerbations was better than that of the BODEx index, although the predictive ability for mortality in elderly adults with COPD was poor for both indices.

Genetic variants of pulmonary SP-D predict disease outcome of COPD in a Chinese population.

BACKGROUND AND OBJECTIVE: Although surfactant protein-D (SP-D) has been suggested as a biomarker for chronic obstructive pulmonary disease (COPD), the relationship between genetic variants of SP-D and disease outcome of COPD remains unknown. We hypothesized that genetic polymorphisms of SP-D are associated with COPD-related phenotypes and disease prognosis. METHODS: A hospital-based, case-controlled study was conducted prospectively. Six single nucleotide polymorphisms of the SFTPD gene were determined for genetic association analysis. Inflammatory cytokines and SP-D serum level were quantified. Frequency of exacerbation and change of lung function were assessed. All-cause 3-year mortality was registered. RESULTS: We studied 320 smokers (192 with COPD and 128 at-risk for COPD) who were prospectively monitored for at least 3 years. The serum levels of SP-D in COPD patients were significantly associated with the degree of airflow obstruction and frequency of exacerbation. Haplotype association analysis revealed that haplotype G-G-C-C-A was associated with lower risk of COPD (P = 0.03) in our study population. COPD patients with haplotype G-G-C-C-A had lower serum SP-D levels (P < 0.001), higher rates of positive response to bronchodilator treatment (P = 0.01), more improvement of forced expiratory volume in 1 s in yearly follow-up (P = 0.03) and better 3-year survival rate than COPD patients with non G-G-C-C-A haplotype (P = 0.03). CONCLUSIONS: Genetic haplotype of SP-D may serve as a valuable prognostic indicator in Chinese patients with COPD.

Association of Egr-1 and autophagy-related gene polymorphism in men with chronic obstructive pulmonary disease.

BACKGROUND/PURPOSE: Autophagy is important in cellular homeostasis and control of inflammatory immune response. Increased autophagy has recently been associated with increased cell death and chronic obstructive pulmonary disease (COPD) pathogenesis. Two autophagy regulator genes have been identified: Egr-1 (early growth response), associated with different phenotype expressions in asthma; and, Atg16L1 (autophagy related 16-like 1), a candidate gene responsible for susceptibility to chronic inflammatory diseases. We will explore the role of the Egr-1 and Atg16L1 gene polymorphisms in COPD. METHODS: The genotypes of 151 male smoking patients with COPD and 100 male smoking controls were evaluated by polymerase chain reaction followed by restriction fragment length polymorphism analysis of the Egr-1 (-4071 A → G) rs7729723 and Atg16L-1 (T300A) rs2241880 variants. RESULTS: The G allele of the Egr-1 gene polymorphism was associated with an increased risk of developing COPD [odds ratio (OR), 2.05; 95% confidence interval (CI), 1.15-3.72], and participants with the G allele polymorphism (GG and GA genotypes) had a 2.56-fold higher risk (OR, 2.56; 95% CI, 1.31-5.16) of having COPD than those homozygous for the A allele [35.8% (54/151) vs. 24.0% (24/100); p = 0.007]. Participants with the A allele of the Atg16L1 gene polymorphism (AA and AG genotypes) had a 3.34-fold higher risk (OR, 3.34; 95% CI, 1.32-8.97) of having COPD than those homozygous for the G allele [93.4% (141/151) vs. 81.0% (81/100); p = 0.013]. CONCLUSION: The Egr-1 and Atg16L1 genes' polymorphisms were significant risk factors for susceptibility to COPD. These results demonstrate that autophagy regulator genetic mutations are associated with COPD in male smokers.

Using cluster analysis to identify phenotypes and validation of mortality in men with COPD.

PURPOSE: Cluster analysis has been proposed to examine phenotypic heterogeneity in chronic obstructive pulmonary disease (COPD). The aim of this study was to use cluster analysis to define COPD phenotypes and validate them by assessing their relationship with mortality. METHODS: Male subjects with COPD were recruited to identify and validate COPD phenotypes. Seven variables were assessed for their relevance to COPD, age, FEV(1) % predicted, BMI, history of severe exacerbations, mMRC, SpO(2), and Charlson index. COPD groups were identified by cluster analysis and validated prospectively against mortality during a 4-year follow-up. RESULTS: Analysis of 332 COPD subjects identified five clusters from cluster A to cluster E. Assessment of the predictive validity of these clusters of COPD showed that cluster E patients had higher all cause mortality (HR 18.3, p < 0.0001), and respiratory cause mortality (HR 21.5, p < 0.0001) than those in the other four groups. Cluster E patients also had higher all cause mortality (HR 14.3, p = 0.0002) and respiratory cause mortality (HR 10.1, p = 0.0013) than patients in cluster D alone. CONCLUSION: COPD patient with severe airflow limitation, many symptoms, and a history of frequent severe exacerbations was a novel and distinct clinical phenotype predicting mortality in men with COPD.

Discriminative and predictive properties of multidimensional prognostic indices of chronic obstructive pulmonary disease: a validation study in Taiwanese patients.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a pulmonary disease with systemic involvement. Several multidimensional indices have been developed to predict long-term outcomes. However, these indices have not been compared and validated in Taiwanese patients with COPD. METHODS: A prospective, observational, hospital-based study was designed, and a total of 621 patients were recruited from May 2006 to December 2011. Patients followed at least 1 year were enrolled and 594 patients eligible for inclusion. Three prognostic indices--the ADO (age, dyspnoea and airflow obstruction), BODEx (body mass index, airflow obstruction, dyspnoea and exacerbations), and CPI (the COPD Prognostic Index)--were validated and the predictive power of each was analysed. RESULTS: The median follow-up of the 594 patients was 33 months (range 1-72 months), and the mortality rate was 19.2% (114 deaths). All indices were significantly predictive for all-cause mortality in our validation cohort. Furthermore, the C statistics of the three indices, indicating their predictive accuracy, were all >0.7 (area under the curve of the CPI 0.718, P < 0.001, ADO 0.702, P < 0.001, BODEx 0.702, P < 0.001). CONCLUSIONS: ADO, BODEx and CPI scores are useful predictors of all-cause mortality with significantly discriminative properties in Taiwanese patients with COPD.

Pulmonary function change in patients with Sauropus androgynus-related obstructive lung disease 15 years later.

BACKGROUND/PURPOSE: Little is understood about the clinical course and prognosis of patients with Sauropus androgynus-related obstructive lung disease. The aim of this study was to investigate their clinical manifestations and pulmonary function change 15 years after the acute episode. METHODS: A descriptive, observational study of patients with S androgynus-related obstructive lung disease, diagnosed 15 years ago, was conducted. We evaluated their pulmonary function and the Modified Medical Research Council (MMRC) dyspnea scale. Saint George's Respiratory Questionnaire (SGRQ) was also performed. Age- and forced expiratory volume in one second (FEV1)-matched chronic obstructive pulmonary disease (COPD) patients were used as a reference group for comparison of clinical manifestations. RESULTS: Twenty-nine of 49 patients, diagnosed at our hospital 15 years ago, could be contacted. Four patients died and one patient was ventilator-dependent. Sixteen patients were willing to come to our hospital to have pulmonary function and questionnaire evaluation. The FEV1 of these patients declined only 1.6 ± 21.6 mL/year over a 15-year period. Meanwhile, the severity of their dyspnea and their health-related quality of life were better than age- and FEV1-matched COPD patients as shown by the MMRC dyspnea scale (1.4 ± 0.8 vs. 2.0 ± 1.0; p = 0.037) and symptom domain of the SGRQ (32.6 ± 18.4 vs. 43.5 ± 20.3; p = 0.006). CONCLUSION: After an acute deterioration, patients with S androgynus-related obstructive lung disease had a stationary pulmonary function over a period of 15 years, and their clinical manifestations were less severe than age- and FEV1-matched COPD patients. A further study with a larger sample size may be needed to confirm these findings.

Pneumocystis jirovecii pneumonia in systemic lupus erythematosus from southern Taiwan.

BACKGROUND: Opportunistic infection has been documented in systemic lupus erythematosus with special attention paid to Pneumocystis jirovecii because of the significant morbidity and high mortality. OBJECTIVES: The limited large-scale investigations covering P. jirovecii pneumonia (PCP) in systemic lupus erythematosus following biologics or immunosuppressants therapy prompted us to perform this study in southern Taiwan. METHODS: A retrospective study was completed in 858 hospitalized lupus patients from January 2000 to December 2011. The definite diagnosis of PCP was made by the laboratory detection of Pneumocystis organisms together with consistent clinical and radiological manifestations of PCP. Positive polymerase chain reaction results of sputum samples were not regarded as infection in this study, unless P. jirovecii was the sole pathogen found and pulmonary manifestations resolved following antibiotics for PCP treatment alone. RESULTS: The laboratory identification of Pneumocystis organisms depended on lung biopsy in 2 cases and bronchoalveolar lavage in 3 patients. Five cases, 2 women and 3 men aged 30 to 50 years (41.8 ± 8.8 years), were identified with a 0.6% incidence. None received chemoprophylactics against P. jirovecii infection. All had lupus nephritis and lymphopenia with low CD4 T-cell counts. Prior usages of higher daily prednisolone dosages and concomitant biologics or immunosuppressants were observed in all patients. Pneumocystis jirovecii pneumonia contributed to a high mortality rate (60%). CONCLUSIONS: We report the rare occurrence but high mortality of PCP infection in this study. A consensus guideline addressing prophylactic antibiotics against Pneumocystis organisms in highest-risk lupus patients on biologics or immunosuppressants could be helpful in guiding their management.

Antimicrobial drug-resistant microbes associated with hospitalized community-acquired and healthcare-associated pneumonia: a multi-center study in Taiwan.

BACKGROUND/PURPOSE: Community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) may be caused by potential antimicrobial drug-resistant (PADR) microbes. The aims of this study were to evaluate the incidences and risk factors associated with PADR microbes observed in patients with pneumonia occurring outside the hospital setting in Taiwan. METHODS: We conducted a retrospective study of patients with CAP or HCAP admitted to six medical centers in the northern, central, and southern regions of Taiwan in 2007. The pathogens were evaluated by microbiological specimens within 72 hours after admission. The patients' comorbidities, pathogens, and outcomes were evaluated. The risk factors of PADR microbes were identified by logistic regression analysis. RESULTS: The enrolled patients exhibited HCAP (n=713) and CAP (n=933). The pathogens associated with HCAP (n=383) and CAP (n=441) included Pseudomonas spp. (29%vs. 10%, p<0.001), Klebsiella spp. (24% vs. 25%, p=0.250), Escherichia coli (6% vs. 8%, p=0.369), Haemophilus influnezae (3% vs. 7%, p=0.041), Streptococcus pneumoniae (2% vs. 6%, p=0.003) and methicillin-resistant Staphylococcus aureus (MRSA) (8% vs. 4%, p=0.008). The core pathogens of CAP and HCAP differed among the three regions of Taiwan. PADR microbes, including Pseudomonas spp. (n=191), Acinetobacter spp. (n=41), MRSA (n=49) and cefotaxime- or ceftazidime-resistant Enterbacteriaceae (n=25), were isolated from 13% of patients with CAP and 23% of patients with HCAP. Previous hospitalization, and neoplastic and neurological diseases were significant risk factors for acquiring PADR microbes. CONCLUSION: PADR microbes were common in patients with HCAP and CAP in Taiwan. Broad-spectrum antibiotics targeting PADR microbes should be administered to patients who have undergone previous hospitalization and who exhibit neurological disorders and/or malignancies.

The role of bactericidal/permeability-increasing protein in men with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Bactericidal/permeability-increasing protein (BPI) is a member of the pattern recognition receptors of the innate immune system. Recently, an association between genetic polymorphism in the BPI gene and a risk of airflow decline after transplantation was demonstrated, but whether these findings are reproducible in nontransplantation populations, such as those with COPD, is still unknown. The aim of this study is to explore the role of BPI in COPD. METHODS: The genotypes of 107 patients with COPD and 110 control subjects were evaluated by polymerase chain reaction and polymorphism analysis of the BPI genes and ELISA analysis of the plasma BPI level. All subjects were men over 40 years old who smoked. RESULTS: BPI mutation PstI (T→C) polymorphism in intron 5 was associated with an increased risk of developing COPD (OR 3.73, 95%CI: 1.62-9.10), and the frequency was significantly increased in the COPD group compared with the control group (26/107 [24.3%] vs 12/110 [10.9%], p = 0.002). In addition, COPD patients exhibited a decreased plasma level of BPI compared with the control group (10.6 ± 2.2 vs 23.4 ± 2.1 ng/ml, p < 0.0001). CONCLUSIONS: BPI mutation (PstI in intron 5) and a decreased plasma BPI level were significant risk factors in susceptibility to COPD. These results demonstrate that BPI genetic mutation and impaired BPI production or release may result in airflow obstruction in smokers.

Using post-bronchodilator FEV1 is better than pre-bronchodilator FEV1 in evaluation of COPD severity.

BACKGROUND: The current standards for the diagnosis and treatment of patients with COPD clearly rely on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria based on post-bronchodilator spirometric values. However, clinical evidence for using the post-bronchodilator FEV1 in the severity classification has not been fully investigated. METHODS: Patients with COPD were enrolled and followed up prospectively between October 2006 and January 2011. We compared the observed 3-year risk of all causes and respiratory mortality with the risk predicted by the pre- and post-bronchodilator percent predicted FEV1. Other important phenotypes including BMI, MMRC dyspnea scale, ECOG performance status and severe AECOPD (acute exacerbation) were also compared between the two groups. The different severity classifications of COPD, measured according the GOLD guidelines by post- and pre-bronchodilator percent predicted FEV1 were compared for prediction of mortality. RESULTS: There were 35 deaths among the 300 COPD patients (11.7%). Multivariate analysis showed that the post-bronchodilator percent predicted FEV1 was a significant independent predictor of mortality but pre-bronchodilator percent predicted FEV1 was not (p = 0.008 vs 0.126) and it was more strongly correlated with all studied predictors of outcome than the pre-bronchodilator percent predicted FEV1. Kaplan-Meier analysis showed that the discrimination ability to predict mortality from the GOLD criteria using post bronchodilator percent predicted FEV1 (p = 0.009) was better than using pre-bronchodilator percent predicted FEV1 (p = 0.131). CONCLUSIONS: The post-bronchodilator percent predicted FEV1 is better than the pre-bronchodilator percent predicted FEV1 in the evaluation of the severity of disease in COPD patients and is more accurate in predicting the risk of death by the GOLD classification.

Classifying different types of double triggering based on airway pressure and flow deflection in mechanically ventilated patients.

BACKGROUND: Double-triggering (DT) is a frequent type of patient-ventilator asynchrony and has potentially severe consequences, such as alveolar overdistention or the generation of intrinsic PEEP. However, the first breath of DT could be patient-triggered (DT-P), auto-triggered (DT-A), or ventilator-triggered (DT-V). OBJECTIVE: To differentiate DT-P, DT-A, and DT-V using airway pressure or flow changes during the trigger-delay phase in ventilated patients. METHODS: Fourteen mechanically ventilated patients with DT were included. All patients were on flow-triggered ventilation modes and received either continuous mandatory ventilation or pressure support ventilation. Breaths in which the first breath was associated with an esophageal pressure drop of > 1 cm H(2)O were categorized as DT-P. Breaths in which the first breath occurred at the ventilator set cycle were categorized as DT-V. Breaths in which the first breath occurred earlier than the ventilator set cycle without esophageal pressure drop were categorized as DT-A. The pressure drop and flow change at 0.13 s (PD(0.13) and F(0.13), respectively) in the trigger-delay phase were calculated from the nadir. RESULTS: There were 507 double-triggered breaths: 271 DT-V (53%), 50 DT-A (10%), and 186 DT-P (37%). The PD(0.13) for DT-V, DT-A, and DT-P were 0.16 ± 0.12 cm H(2)O, 0.25 ± 0.17 cm H(2)O, and 1.34 ± 0.67 cm H(2)O, respectively. The F(0.13) for DT-V, DT-A, and DT-P were 2.11 ± 2.31 L/min, 2.64 ± 2.07 L/min, and 16.51 ± 8.02 L/min, respectively. The best discriminatory criteria for differentiating DT-P from DT-V and DT-A, based on the Youden index (sensitivity + specificity - 1) was PD(0.13) ≥ 0.49 cm H(2)O, which had a Youden index of 95%. CONCLUSION: DT-P can be distinguished from DT-V and DT-A by using airway pressure deflections in the trigger-delay phase.

Alterations in respiratory mechanics in mechanically ventilated patients following bronchoalveolar lavage.

BACKGROUND/PURPOSE: Bronchoalveolar lavage (BAL) can be used for a variety of diagnostic purposes in mechanically ventilated patients. BAL can cause changes in respiratory mechanics. However, the risk factors associated with these changes remain unknown. The current study tried to identify the risk factors that contribute to changes in respiratory mechanics following BAL. METHODS: Changes in respiratory mechanics were assessed in 56 mechanically ventilated patients who received BAL using an interrupter method under constant flow. RESULTS: Intrinsic positive end-expiratory pressure (PEEPi) was correlated significantly with changes in respiratory system resistance and compliance following BAL in mechanically ventilated patients (p = 0.003). In 14 patients with PEEPi > 1 cmH2O, maximal resistance (Rmax) before BAL was 22.5 +/- 5.9 cmH2O/L/S, increasing to 31.6 +/- 8.5 cmH2O/L/S immediately after BAL, and remaining high (28.4 +/- 7.5 cmH2O/L/S) 30 minutes later (p < 0.001). Increase in minimal resistance (Rmin), delta resistance (DeltaR), and decrease in compliance followed the same time trend. In 42 patients with PEEPi < or = 1 cmH2O, Rmax before BAL was 15.5 +/- 3.5 cmH2O/L/S, increasing to 17.6 +/- 4.6 cmH2O/L/S immediately after BAL, and decreasing to 16.6 +/- 4.3 cmH2O/L/S (p < 0.001) 30 minutes later. Increase in Rmin, DeltaR and decrease in compliance were similar to those seen with Rmax. Increases in Rmax, Rmin and DeltaR, and decrease in compliance following BAL were significantly higher in patients with significant PEEPi than in those without throughout the recording period (p < 0.001). CONCLUSION: Patients with significant PEEPi experienced greater changes in respiratory mechanics than those without. Physicians should be cautious when performing BAL in such patients.