FEV1 Percent Research Articles

Co-inhibitory receptors in female asthmatic patients: Correlation with IL-17 and IL-26

Background: Asthma is an immunological disorder in which T helper 2 (Th2)-type cells and inflammatory cytokines have a prominent role in its pathogenesis. B- and T-lymphocyte attenuator (BTLA), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) are co-inhibitory receptors that regulate T cell activation. Objective: In the present study of asthmatic patients we measured the soluble isoforms of BTLA (sBTLA), CTLA-4 (sCTLA-4) and PD-1 (sPD-1) in induced sputum fluid with the aim to evaluate their utility as responsible for exacerbation. Methods: Eighty patients with asthma and 30 healthy controls (HC) were included in the study. Sputum fluid concentrations of sBTLA, sCTLA-4 and sPD-1 were measured with ELISA. Comparisons were made with Mann-Whitney U test and correlations with IL-17, IL-26 levels and FEV1 (%) were assessed with Spearman’s Rank correlation test. Results: sBTLA levels were significantly higher in the severe and moderate asthmatic patients compared to healthy controls. Significant differences were observed between severe and moderate asthmatics (p < 0.0001). No significant differences were found between mild asthmatics and healthy controls (p = 0.799). Soluble PD-1 levels were higher in severe and moderate asthmatic patients compared to HC and no significant difference was observed between these two asthmatic groups (p = 0.124). Mild asthmatics and control subjects expressed similar sPD-1 levels (p = 0.856). Soluble CTLA-4 was exclusively expressed in certain severe asthmatic patients. IL-17 inflammatory cytokine was significantly correlated with BTLA and sPD-1. IL-17 and IL-26 cytokines were highly expressed in sputum asthmatic groups compared to sputum from HC. Severe asthmatic group was characterized by the highest levels of both IL-17 and IL-26 mediators. Soluble BTLA correlates positively with IL-17 (r = 0.817; p < 0.0001) and IL-26 (r = 0.805; p < 0.0001) inflammatory cytokines. IL-17 and IL-26 levels were associated with the asthma clinical severity from severe to mild asthma (p < 0.0001). The inflammatory cytokines IL-17 and IL-26 were positively correlated with the percentages of macrophages, PNN and FEV1 (%). Conclusion: Here, we provide the first report on the increased expression of sBTLA and sPD-1 in induced sputum of severe asthmatics. IL-26 and IL-17 appeared as a novel proinflammatory axis. Both sBTLA and sPD-1 might be involved in the pathogenesis of asthma and were associated with a poor prognosis.

GLCCI1 rs37973

Glucocorticoids are the primary anti-inflammatory therapy for asthma, but their effects are characterized by some interindividual variability that might have a genetic basis.We aimed to determine the relationship between pulmonary function change and the variant of the glucocorticoid-induced transcript 1 (GLCCI1) gene in patients with asthma receiving long-term ICS treatment, the association of GLCCI1 genotypes and the level of GLCCI1 expression and cytokines production.A total of 418 patients with asthma, including 25 individuals from 11 families with a history of asthma, were enrolled. The effects of single-nucleotide polymorphisms (SNPs) in GLCCI1 on changes in lung function in response to inhaled glucocorticoids were assessed. The expression levels of GLCCI1 mRNA and cytokines were also measured.The SNP rs37973 in GLCCI1 was independently associated with changes in forced expiratory volume at one second (FEV1) and FEV1%pred. Individuals homozygous for the wild-type allele who had a percent FEV1 change greater than 5% were more common than individuals homozygous for the rare allele. When patients were stratified according to genotype, GLCCI1 expression was enhanced upon administration of low-dose dexamethasone among patients with the rs37973 A allele; however, GG homozygotes required high-dose dexamethasone to achieve enhanced GLCCI1 expression. Furthermore, the levels of some cytokines were significantly reduced after glucocorticoid treatment in individuals with the AA and AG genotypes.The genetic variant rs37973 in GLCCI1 is associated with poorer clinical therapeutic response to inhaled glucocorticoids in a Chinese asthma population.

Association between increased small airway obstruction and asbestos exposure in patients with asbestosis.

Asbestos exposure may cause asbestos-related lung diseases including asbestosis, pleural abnormalities and malignancies. The role of asbestos exposure in the development of small airway obstruction remains controversial. Anatomic and physiologic small airway abnormalities may develop as part of the pathophysiologic process of asbestosis. We hypothesized that inhalation of asbestos may induce small airway defects in addition to asbestosis and pleural abnormalities. In total, 281 patients with newly diagnosed asbestosis were evaluated. Clinical data were collected from the patients' medical charts. The patients were classified into various stages according to their chest X-ray findings using the International Labour Organization classification. Pulmonary function was evaluated by plethysmography and the forced oscillation technique. Expiratory flow, including the predicted values of the maximum expiratory flow between 25% and 50% of the forced vital capacity (MEF25-50 ), was significantly lower in the different stages of asbestosis. Accordingly, the predicted percentage of R5 -R20 was significantly higher with increasing stages of asbestosis. Furthermore, the duration of exposure to asbestos was significantly associated with the forced expiratory volume in the first second (FEV1 )/forced vital capacity (FVC) ratio and the predicted percentage of MEF25 or MEF50 according to the regression analysis in non-smoking patients with asbestosis. The predicted percentage of FEV1 or the FEV1 /FVC ratio was significantly lower and the predicted percentage of R5 -R20 was significantly higher in smokers than non-smokers. The patients with asbestosis have small airway obstructive defects that are significantly associated with asbestos exposure.

Adherence to inhaled therapies of COPD patients from seven Latin American countries: The LASSYC study.

BackgroundThis study assessed the adherence profiles to inhaled therapies and the agreement between two patient self-report adherence methods in stable COPD lpatients from seven Latin American countries.MethodsThis observational, cross-sectional, multinational, multicenter study involved 795 COPD patients (post-bronchodilator forced expiratory volume in 1 second/forced vital capacity [FEV1/FVC] <0.70). Adherence to inhaled therapy was assessed using the specific Test of Adherence to Inhalers (10-item TAI) and the generic 8-item Morisky Medication Adherence Scale (MMAS-8) questionnaires. The percentage agreement and the kappa index were used to compare findings.Results59.6% of patients were male (69.5±8.7 years); post-bronchodilator FEV1 percent predicted was 50.0±18.6%. Mean values for 10-item TAI and MMAS-8 questionnaires were 47.4±4.9 and 6.8±1.6, respectively. Based on the TAI questionnaire, 54.1% of patients had good, 26.5% intermediate, and 19.4% poor adherence. Using the MMAS-8 questionnaire, 51% had high, 29.1% medium, and 19.9% low adherence. According to both questionnaires, patients with poor adherence had lower smoking history, schooling but higher COPD Assessment Test score, exacerbations in the past-year and post-bronchodilator FEV1. The agreement between 10-item TAI and MMAS-8 questionnaires was moderate (Kappa index: 0.42; agreement: 64.7%).ConclusionSuboptimal adherence to medication was frequent in COPD patients from Latin America. Low adherence was associated with worse health status impairment and more exacerbations. There was inadequate agreement between the two questionnaires. Greater effort should be made to improve COPD patients’ adherence to treatment, and assessment of adherence with more specific instruments, such as the TAI questionnaire, would be more convenient in these patients.Clinical Trial RegistrationNCT02789540

Pulmonary function disparities exist and persist in Hispanic patients with cystic fibrosis: A longitudinal analysis.

Hispanic patients with cystic fibrosis (CF) have decreased life expectancy compared to non-Hispanic white patients. Pulmonary function is a main predictor of life expectancy in CF. Ethnic differences in pulmonary function in CF have been understudied. The objective was to compare longitudinal pulmonary function between Hispanic and non-Hispanic white patients with CF. This cohort study of 15 018 6-25 years old patients in the CF Foundation Patient Registry from 2008 to 2013 compared FEV1 percent predicted and longitudinal change in FEV1 percent predicted in Hispanic to non-Hispanic white patients. We used linear mixed effects models with patient-specific slopes and intercepts, adjusting for 14 demographic and clinical variables. We did sub-analyses by CFTR class, F508del copies, and PERT use. Hispanic patients had lower FEV1 percent predicted (79.9%) compared with non-Hispanic white patients (85.6%); (-5.8%, 95%CI -6.7% to -4.8%, P < 0.001), however, there was no difference in FEV1 decline over time. Patients on PERT had a larger difference between Hispanic and non-Hispanic white patients in FEV1 percent predicted than patients not on PERT (-6.0% vs -4.1%, P = 0.02). The ethnic difference in FEV1 percent predicted was not statistically significant between CFTR classes (Class I-III: -6.1%, Class IV-V: -5.9%, Unclassified: -5.7%, P > 0.05) or between F508del copies (None: -7.6%, Heterozygotes: -5.6%, Homozygotes: -5.3%, P > 0.05). Disparities in pulmonary function exist in Hispanic patients with CF early in life and then persist without improving or worsening over time. It is valuable to investigate the factors contributing to pulmonary function in Hispanic patients with CF.

External Validation of the COmorbidity Test

ABSTRACTThe COmorbidity TEst (COTE) is a Chronic Obstructive Pulmonary Disease (COPD)-specific co-morbidity score created to predict mortality. Before its wide application at the University of New Mexico we intended to validate it. The study was conducted at the University of New Mexico Hospital (UNMH) in Albuquerque, NM, USA, a tertiary academic hospital. Consecutive patients with the clinical diagnosis of COPD were identified using the hospital's medical records system and included if they were older than 40 years, had smoked at least 20 pack-years and their post bronchodilator forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) was <0.7 without an alternative diagnosis. The data collected included demographics, co-morbidities as described in the COTE, COPD-specific therapies, spirometry results and mortality. Of 317 patients 51.4% were male, average age was 65.6 ± 9.6 years and the mean post-bronchodilator FEV1 percent predicted (FEV1%) was 52.9 ± 16.9%. 31 (9.8%) patients were on triple long-acting bronchodilator inhaler therapy, 88 (27.8%) on two long-acting bronchodilators and 163 (51.4%) on at least one long-acting bronchodilator. The median follow-up was 3.5 years (IQR = 1.9–6.9). Fifty four patients died by the end of the follow-up period and their median COTE of 4 (IQR = 1–8) was significantly higher than for the survivors with COTE = 1 (IQR = 0–6; p = 0.002). In univariable analyses COTE was positively associated while FEV1%, body mass index (BMI) and gender were negatively associated with all-cause mortality. In multivariable analysis BMI, FEV1% and COTE remained independent predictors for mortality. The COTE is an independent predictor of mortality for COPD patients at UNMH.

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OBJECTIVES/SPECIFIC AIMS: In this pilot case-control study, the metabolome was quantified in subjects with previously measured serum and clinical biomarkers. The serum metabolome was then integrated with existing serum and clinical biomarkers of WTC-exposed firefighters to identify pathways significant to loss of lung function following acute PM-exposure. This robust subset of metabolite and serum biomarkers may be clinically relevant to predicting progression to lung disease in a larger cohort. METHODS/STUDY POPULATION: Serum drawn within 6 months of 9/11 was analyzed in this pilot. Clinical measures were obtained from electronic medical records. Never-smoking, male, WTC-exposed firefighters with normal pre-9/11 lung function were segregated based on FEV1 percent predicted (FEV1 %Pred) at symptomatic presentation. Cases of WTC-LI (FEV1 %Pred &lt;LLN, n=15) and controls (n=15) were identified from previous cohorts. Ultrahigh performance liquid chromatography tandem mass spectroscopy quantified the metabolomic fingerprints of a group with previously assessed (by multiplex panels; ELISA and Luminex) serum chemokines and cytokines. High-dimensional data analysis and dimension reduction techniques integrated metabolites, cytokines, chemokines, and clinical data to identify pathways of WTC-LI on curated data. Random Forest (RF) out-of-bag estimated success rates were used to measure classification utility of the refined biomarker profile. Principal components analysis (PCA) was used to visualize class separation produced by the refined profile. RESULTS/ANTICIPATED RESULTS: Of the 765 metabolites detected, 580 metabolites were quantified in more than 80% of subjects/group with relative standard deviation ≥15%. Relevant chemokines, cytokines, and clinical biomarkers were included based on previously established clinical importance. Initial PCA explained 34.7% of the variance in the first 3 components. RF was used to identify the top 5% of biomarkers important to class separation. RF of the refined biomarker profile correctly classified cases and controls with a 96.7% estimated success rate. A PCA of the refined metabolic profile now explained 46.2% of the variance in components 1–3, demonstrating improved class separation. Differentiators between cases of WTC-LI and controls included elevated sphingolipids in cases of WTC-LI. The metabolic-inflammatory serum biomarkers MDC, Apo AI, GM-CSF, and heart rate play an important role in class separation. Phospholipids and lysolipids also appeared to differentiate cases of WTC-LI from controls. Specifically, several glycero-phosphatidylcholines (GPC) were elevated in cases of WTC-LI. DISCUSSION/SIGNIFICANCE OF IMPACT: High-dimensional data analysis on the metabolic fingerprints, serum, and clinical biomarker data of a subset of WTC-exposed 9/11 rescue workers has identified pathways associated with the loss of lung function. Sphingolipids, known to function as inflammatory signaling mediators, are thought to play important roles in lung function under both physiological and pathological conditions. Changes in sphingolipid metabolism have been linked to several pulmonary disorders, including asthma, COPD, and acute lung injury. Interestingly, a relation between sphingolipid metabolism and the metabolic-inflammatory pathway is suggested by similarities observed in PCA. Findings of elevated GPCs are similar to COPD literature. Higher levels of GPCs could correspond to elevated levels of lysophosphatidic acid (LPA), a ligand of RAGE. RAGE is a known proinflammatory mediator; LPA species have well-described roles as lipid signaling molecules, function as synthetic intermediates in other metabolic pathways, and were found to be predictive of WTC-LI. Since metabolites are more proximal markers of disease processes, metabolites could capture the complexity of past exposures and, therefore, may better inform treatment. These pathways warrant further investigation into their mechanisms and therapeutic importance.

Body composition and micronutrient deficiencies in patients with an acute exacerbation of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a multisystem disorder. Abnormal body composition (BC) and micronutrient deficiencies (MD) contribute significantly to morbidity associated with acute exacerbations of COPD (AECOPD). COPD is a major health problem in Western Sydney. To study the pattern of BC and MD in patients admitted with an AECOPD to Western Sydney. The BC and serum levels of selected micronutrients were recorded in prospective, consecutive patients admitted to hospital with AECOPD in Western Sydney. A total of 94 patients was enrolled, 43% female, and the average age was 69.8 ± 8.2 years (SD). Admission spirometry revealed a mean spirometric ratio of 0.42 ± 0.14 (SD) and a severely reduced mean percentage FEV1 of predicted at 29.1% ± 11.6 (SD). A total of 51% of the population was overweight or obese, with an average body mass index of 25.9 ± 7.7 kg/m2 (SD). When fat-free mass (FFM) was also considered 23% were cachectic, 9% had muscle atrophy and 6% were semi-starved. Vitamin D deficiency (<50 nmol/L) was present in 53% and vitamin B12 deficiency (<222 pmol/L) was present in 31%. Anaemia was present in 30%, with 38% of these being iron deficient. Living status (alone or with family) was not associated with BC or micronutrient deficiencies (MD). Patients with ≥2 hospital admissions for AECOPD had a significantly lower mean B12 level (280.5 ± 143.0 pmol/L (SD) vs 360.5 ± 198.1 pmol/L (SD) P = 0.042). The malnutrition screening tool, a questionnaire-based assessment of malnutrition used by the local health area did not accurately predict patients with abnormal BC or those with >2 MD. In patients admitted with AECOPD, the majority of subjects were overweight or obese, with a low FFM. MD, in particular B12 and vitamin D, were common. Interventional studies addressing BC and MD are required to assess potential improvements in AECOPD-related morbidity and mortality.

Alpha-1 Antitrypsin PiMZ Genotype Is Associated with Chronic Obstructive Pulmonary Disease in Two Racial Groups.

Alpha-1 antitrypsin deficiency, caused primarily by homozygosity for the Z allele of the SERPINA1 gene, is a well-established genetic cause of chronic obstructive pulmonary disease (COPD). Whether the heterozygous PiMZ genotype for alpha-1 antitrypsin confers increased risk for COPD has been debated. We analyzed 8,271 subjects in the Genetic Epidemiology of COPD (COPDGene) Study, hypothesizing that PiMZ would independently associate with COPD and COPD-related phenotypes. The COPDGene Study comprises a multiethnic, cross-sectional, observational cohort of non-Hispanic white and African American current and former smokers with at least 10 pack-years of smoking who were enrolled for detailed clinical and genetic studies of COPD and COPD-related traits. We performed multivariate logistic regression analysis for moderate to severe COPD and assessed Pi genotype with other relevant covariates in models stratified by race. We analyzed quantitative characteristics on the basis of volumetric computed tomography with generalized linear models controlling for genotype, scanner type, and similar covariates. White PiMZ COPDGene subjects had significantly lower lung function, FEV1 percent predicted (68 ± 28 vs. 75 ± 27; P = 0.0005), and FEV1/FVC ratio (0.59 ± 0.18 vs. 0.63 ± 0.17; P = 0.0008), as well as more radiographic emphysema (P = 0.001), than subjects without alpha-1 antitrypsin Z risk alleles. Similarly, African American PiMZ subjects had lower lung function, FEV1 percent predicted (65 ± 33 vs. 84 ± 25; P = 0.009) and FEV1/FVC (0.61 ± 0.21 vs. 0.71 ± 0.15; P = 0.03). In the COPDGene Study, we demonstrate that PiMZ heterozygous individuals who smoke are at increased risk for COPD and obstructive lung function impairment compared with Z-allele noncarriers, regardless of race. Although severe alpha-1 antitrypsin deficiency is uncommon in African Americans, our study adds further support for initial targeted detection of all subjects with COPD for alpha-1 antitrypsin deficiency, including African Americans. Clinical trial registered with www.clinicaltrials.gov (NCT00608784).

A novel endpoint for exacerbations in asthma to accelerate clinical development: a post-hoc analysis of randomised controlled trials

Occurrence of severe asthma exacerbations are the cornerstone of the evaluation of asthma management, but severe asthma exacerbations are rare events. Therefore, trials that assess drug efficacy on exacerbations are done late in clinical development programmes. We aimed to establish an endpoint capturing clinically relevant deteriorations (diary events) that, when combined with severe exacerbations, create a composite outcome (CompEx). CompEx needs to strongly mirror results seen with the severe exacerbation-validated outcome, to allow the design of clinical trials of shorter duration and that include fewer patients than trials assessing severe exacerbations. Data from 12 asthma trials of 6 months or 12 months duration and, with standardised collection of exacerbations and diary card variables, were used to construct and test CompEx. The study populations had a mean age of 35-53 years, 59-69% were female, and had a mean FEV1 percentage of predicted normal of 63-84%. With data from five trials, we established a series of diary events based on peak expiratory flow (P), reliever use (R), symptoms (S), awakenings (A), and threshold values for change from baseline and slopes to assess trends. For the development phase, we evaluated different variable combinations and deterioration criteria to select the most robust algorithm to define a diary event for the composite outcome. We defined a composite outcome, CompEx, as first occurrence of a diary event or a severe exacerbation. We assessed the performance of CompEx in seven trials by comparing the event frequency, treatment effect (hazard ratio; HR), and the sample size needed for future trials for the CompEx versus episodes of severe exacerbations. CompEx (based on PRS) was the algorithm that best fulfilled our two-set criteria. When censored at 3 months, CompEx resulted in 2·8 times more events than severe exacerbations, and while preserving the treatment effect observed on severe exacerbations (CompEx over severe exacerbation average HR 1·01). The increased number of events, together with the sustained treatment effect, resulted in a large net gain in power, with a 67% mean reduction in the number of patients required in a drug trial for severe exacerbations. In six of seven comparisons tested, CompEx reduced the sample size needed by at least 50%. Validation of independent test populations confirmed the ability of CompEx to increase event frequencies, preserve treatment effect, and reduce the number of patients needed. CompEx is a composite outcome for evaluation of new asthma therapies. CompEx allows design of shorter trials that require fewer patients than studies of severe exacerbations, while preserving the ability to show a treatment effect compared with severe exacerbations. AstraZeneca.

Increasing Severity of Pneumoconiosis Among Younger Former US Coal Miners Working Exclusively Under Modern Dust-Control Regulations.

Coal workers' pneumoconiosis (CWP) steadily declined among US miners following dust control regulations in 1970. In 2000, severe forms of this disease reemerged among young miners, and are well described among working-but not former-miners. Black lung benefits program (BLBP) data (2001 to 2013) were used to estimate respiratory disease burden among former miners including: (1) CWP (simple; advanced CWP, and progressive massive fibrosis [CWP/PMF]); and (2) respiratory impairment (FEV1 percent reference: mild, moderate, ≥moderately-severe). Among 24,686 claimants, 8.5% had advanced CWP/PMF; prevalence was highest among younger (less than or equal to 56 years: 10.8%) and older (greater than 70 years: 8.4%) miners and those who began work after versus before 1970 (8.3% vs. 4.0%). BLBP claims provide potentially useful data for monitoring the burden and severity of coal mine dust lung disease, and assessing efficacy of protective regulations.

Effects of a simple prototype respiratory muscle trainer on respiratory muscle strength, quality of life and dyspnea, and oxidative stress in COPD patients: a preliminary study.

BackgroundThe aim of this study was to evaluate the efficiency of a simple prototype device for training respiratory muscles in lung function, respiratory muscle strength, walking capacity, quality of life (QOL), dyspnea, and oxidative stress in patients with COPD.MethodsThirty COPD patients with moderate severity of the disease were randomized into three groups: control (n=10, 6 males and 4 females), standard training (n=10, 4 males and 6 females), and prototype device (n=10, 5 males and 5 females). Respiratory muscle strength (maximal inspiratory pressure [PImax] and maximal expiratory pressure [PEmax]), lung function (forced vital capacity [FVC], percentage of FVC, forced expiratory volume in 1 second [FEV1], percentage of FEV1 [FEV1%], and FEV1/FVC), 6-minute walking distance (6MWD), QOL, and oxidative stress markers (total antioxidant capacity [TAC]), glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) were evaluated before and after 6 weeks of training. Moreover, dyspnea scores were assessed before; during week 2, 4, and 6 of training; and at rest after training.ResultsAll parameters between the groups had no statistical difference before training, and no statistical change in the control group after week 6. FVC, FEV1/FVC, PImax, PEmax, QOL, MDA, and NO showed significant changes after 6 weeks of training with either the standard or prototype device, compared to pre-training. FEV1, FEV1%, 6MWD, TAC, and GSH data did not change statistically. Furthermore, the results of significant changes in all parameters were not statistically different between training groups using the standard and prototype device. The peak dyspnea scores increased significantly in week 4 and 6 when applying the standard or prototype device, and then lowered significantly at rest after 6 weeks of training, compared to pre-training.ConclusionThis study proposes that a simple prototype device can be used clinically in COPD patients as a standard device to train respiratory muscles, improving lung function and QOL, as well as involving MDA and NO levels.

Piperacillin-tazobactam versus cefepime incidence of acute kidney injury in combination with vancomycin and tobramycin in pediatric cystic fibrosis patients

Cystic fibrosis (CF) patients often receive prolonged courses of broad spectrum antibiotics, such as piperacillin-tazobactam or cefepime in combination with vancomycin and tobramycin. The objective of this study was to determine the difference in AKI for pediatric CF patients receiving piperacillin-tazobactam or cefepime in combination with vancomycin and tobramycin. IRB approval from a single CF center was obtained for this retrospective cohort study. Charts were evaluated from December 1, 2008 to June 30,2015. Patients were included if they had a diagnosis of CF, age 30 days to 18 years, and received intravenous vancomycin, tobramycin, and piperacillin-tazobactam or cefepime. The primary outcome was difference of AKI incidence in patients receiving piperacillin-tazobactam or cefepime, as defined by modified pediatric risk, injury, failure, loss, end stage renal disease (pRIFLE) criteria. Seventy-one patients were included with a median (interquartile range) age 11 years (7-16) and weight 36.2 kg (22.7-50). AKI was identified in 54.5% (18/33) of patients receiving piperacillin-tazobactam and 13.2% (5/38) of patients receiving cefepime (P ≤ 0.0001). One patient receiving piperacillin-tazobactam experienced acute renal failure. There was a slight difference in length of admission (13 vs 10 days, P = 0.042), but no difference in days to maximum SCr (6 vs 3, P = 0.127) nor FEV1 percent predicted on admission (69% vs 65%, P = 1.00). AKI occurred in nearly 55% of patients with piperacillin-tazobactam therapy versus 13% of patients with cefepime therapy, which suggests cefepime may be preferred in combination with vancomycin and tobramycin for pediatric CF patients.

A clinical tool to calculate post-transplant survival using pre-transplant clinical characteristics in adults with cystic fibrosis.

We previously identified factors associated with a greater risk of death post-transplant. The purpose of this study was to develop a clinical tool to estimate the risk of death after transplant based on pre-transplant variables. We utilized the Canadian CF registry to develop a nomogram that incorporates pre-transplant clinical measures to assess post-lung transplant survival. The 1-, 3-, and 5-year survival estimates were calculated using Cox proportional hazards models. Between 1988 and 2012, 539 adult Canadians with CF received a lung transplant with 208 deaths in the study period. Four pre-transplant factors most predictive of poor post-transplant survival were older age at transplantation, infection with B. cepacia complex, low FEV1 percent predicted, and pancreatic sufficiency. A nonlinear relationship was found between risk of death and FEV1 percent predicted, age at transplant, and BMI. We constructed a risk calculator based on our model to estimate the 1-, 3-, and 5-year probability of survival after transplant which is available online. Our risk calculator quantifies the risk of death associated with lung transplant using pre-transplant factors. This tool could aid clinicians and patients in the decision-making process and provide information regarding the timing of lung transplantation.

Objective Measurement of Adherence to Out-Patient Airway Clearance Therapy by High-Frequency Chest Wall Compression in Cystic Fibrosis.

Objective measures of adherence to high-frequency chest wall compression (HFCWC), a form of airway clearance therapy for patients with cystic fibrosis, are lacking. We used a novel electronic monitoring device integrated into an HFCWC vest to measure adherence compared with self-reported adherence. We determined factors that influenced adherence and how adherence correlated with baseline pulmonary function and pulmonary exacerbations. Data were collected by direct measurement of date, time of day, and duration of HFCWC use to determine the number of daily treatments and daily duration of treatments. Chart review provided prescribed airway clearance therapy treatment and demographic and clinical information. Subject and caregiver report of the daily number of airway clearance therapy treatments was obtained by telephone interviews. Analysis used 2-sample and paired t test, analysis of variance, and linear regression. Average adherence was 69%. Adherence was highest in children (82%, P = .02) and those receiving assistance with treatment (82%, P < .001). Subjects overestimated therapy duration from a mean ± SD of 127 ± 169% by adults to 19.2 ± 26.3% by parents or guardians of children. Average adherence decreased with increasing prescribed therapy time (P = .02). Average daily therapy time and adherence had significant positive associations with baseline FEV1 percent of predicted (P = .02 and P = .02, respectively) and negative associations with pulmonary exacerbations during the pre-study period and at baseline (P = .044 and P = .02, respectively). Greater adherence to HFCWC measured directly by a novel recorder was associated with better baseline pulmonary function and fewer exacerbations in the pre-study and baseline period. Adherence decreased with age and prescribed therapy time and increased with therapy assistance. Self-report overestimation is large and thus not an accurate measure of adherence.

Effect of allergic bronchopulmonary aspergillosis on FEV1 in children and adolescents with cystic fibrosis: a European Cystic Fibrosis Society Patient Registry analysis

ObjectiveTo evaluate the effect of allergic bronchopulmonary aspergillosis (ABPA) on FEV1 percent predicted in children and adolescents with cystic fibrosis.DesignLongitudinal data analysis (2008–2010).SettingPatients participating in the European Cystic Fibrosis Society...

A New Approach for Identifying Patients with Undiagnosed Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is often unrecognized and untreated. To develop a method for identifying undiagnosed COPD requiring treatment with currently available therapies (FEV1 <60% predicted and/or exacerbation risk). We conducted a multisite, cross-sectional, case-control study in U.S. pulmonary and primary care clinics that recruited subjects from primary care settings. Cases were patients with COPD and at least one exacerbation in the past year or FEV1 less than 60% of predicted without exacerbation in the past year. Control subjects were persons with no COPD or with mild COPD (FEV1 ≥60% predicted, no exacerbation in the past year). In random forests analyses, we identified the smallest set of questions plus peak expiratory flow (PEF) with optimal sensitivity (SN) and specificity (SP). PEF and spirometry were recorded in 186 cases and 160 control subjects. The mean (SD) age of the sample population was 62.7 (10.1) years; 55% were female; 86% were white; and 16% had never smoked. The mean FEV1 percent predicted for cases was 42.5% (14.2%); for control subjects, it was 82.5% (15.7%). A five-item questionnaire, CAPTURE (COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk), was used to assess exposure, breathing problems, tiring easily, and acute respiratory illnesses. CAPTURE exhibited an SN of 95.7% and an SP of 44.4% for differentiating cases from all control subjects, and an SN of 95.7% and an SP of 67.8% for differentiating cases from no-COPD control subjects. The PEF (males, <350 L/min; females, <250 L/min) SN and SP were 88.0% and 77.5%, respectively, for differentiating cases from all control subjects, and they were 88.0% and 90.8%, respectively, for distinguishing cases from no-COPD control subjects. The CAPTURE plus PEF exhibited improved SN and SP for all cases versus all control subjects (89.7% and 78.1%, respectively) and for all cases versus no-COPD control subjects (89.7% and 93.1%, respectively). CAPTURE with PEF can identify patients with COPD who would benefit from currently available therapy and require further diagnostic evaluation. Clinical trial registered with clinicaltrials.gov (NCT01880177).

Race is associated with differences in airway inflammation in patients with asthma

African American subjects have a greater burden from asthma compared with white subjects. Whether the pattern of airway inflammation differs between African American and white subjects is unclear. We sought to compare sputum airway inflammatory phenotypes of African American and white subjects treated or not with inhaled corticosteroids (ICSs; ICS+ and ICS-, respectively). We performed a secondary analysis of self-identified African American and white subjects with asthma enrolled in clinical trials conducted by the National Heart, Lung, and Blood Institute-sponsored Asthma Clinical Research Network and AsthmaNet. Demographics, clinical characteristics, and sputum cytology after sputum induction were examined. We used a sputum eosinophil 2% cut point to define subjects with either an eosinophilic (≥2%) or noneosinophilic (<2%) inflammatory phenotype. Among 1018 participants, African American subjects (n=264) had a lower FEV1 percent predicted (80% vs 85%, P<.01), greater total IgE levels (197 vs 120 IU/mL,P<.01), and a greater proportion with uncontrolled asthma (43% vs 28%, P<.01) compared with white subjects (n=754). There were 922 subjects in the ICS+group (248 African American and 674 white subjects) and 298 subjects in the ICS- group (49 African American and 249 white subjects). Eosinophilic airway inflammation was not significantly different between African American and white subjects in either group (percentage with eosinophilic phenotype: ICS+group: 19% vs 16%, P=.28; ICS- group: 39% vs 35%, P=.65; respectively). However, when adjusted for confounding factors, African American subjects were more likely to exhibit eosinophilic airway inflammation than white subjects in the ICS+group (odds ratio, 1.58; 95% CI, 1.01-2.48; P=.046) but not in the ICS-group (P=.984). African American subjects exhibit greater eosinophilic airway inflammation, which might explain the greater asthma burden in this population.

Pulmonary Rehabilitation Improves Outcomes in Chronic Obstructive Pulmonary Disease Independent of Disease Burden.

Current practice guidelines recommend pulmonary rehabilitation as an adjunct to standard pharmacologic therapy for individuals with moderate to severe chronic obstructive pulmonary disease (COPD). Whether pulmonary rehabilitation benefits all subjects with COPD independent of baseline disease burden is not known. To test whether pulmonary rehabilitation benefits patients with COPD independent of baseline exercise capacity, dyspnea, and lung function. Data from a prospectively maintained database of participants with COPD enrolled in pulmonary rehabilitation at the University of Alabama at Birmingham from 1996 to 2013 were retrospectively analyzed. Subjects were divided into four quartiles based on their baseline level of dyspnea as assessed by the San Diego Shortness of Breath Questionnaire at the initial visit. Similar quartiles were assessed for FEV1 percent predicted as well as the 6-minute-walk distance (6MWD). The primary outcome was the change in quality of life as measured by the 36-item Short Form Health Survey (SF-36). Secondary outcomes were change in dyspnea, 6MWD, and depression scores assessed using the Beck Depression Inventory-II. Differences between baseline and final scores were compared using paired t tests and across quartiles using analysis of variance. A total of 229 subjects were included. Their mean age was 66.5 (SD, 9) years. Ninety-one (40%) were female, and 42 (18%) were African American. The mean FEV1 percent predicted was 46.3% (20.0%). On completion of pulmonary rehabilitation, clinically significant improvements were seen in most components of SF-36: physical function, 11.5 (95% confidence interval [CI], 7.4-15.5; P < 0.001); health perception, 2.1 (95% CI, -0.7 to 4.8; P = 0.12); physical role, 16.7 (95% CI, 10.3-23.1; P < 0.001); emotional role, 14.7 (95% CI, 7.1-22.3; P < 0.001); social function, 16.4 (95% CI, 11.3-21.5; P < 0.001); mental health, 5.4 (95% CI, 2.6-8.3; P < 0.001); pain, 5 (95% CI, 1-9.1; P = 0.02); vitality, 12.4 (95% CI, 8.8-16.1; P < 0.001); and depression, 0.01 (95% CI, -0.11 to 0.07; P = 0.54). There was no difference in improvement in SF-36 across quartiles of San Diego Shortness of Breath Questionnaire, 6MWD, and FEV1 percent predicted. Pulmonary rehabilitation results in significant improvement in quality of life, dyspnea, and functional capacity independent of baseline disease burden.

Occurrence of COPD in Patients with Respiratory Allergy: A Clinico-Spirometric Evaluation in a Tertiary Hospital, Kolkata.

Smoking is established as the most important causative factor responsible for Chronic Obstructive Pulmonary Disease (COPD). Occurrence of allergy in COPD patients causes acute exacerbation of this disease, but role of allergy is not established in aetiopathogenesis of COPD. The present study was aimed at evaluation of occurrence of COPD in patients having symptoms suggestive of respiratory allergy. An observational cross-sectional study was conducted to evaluate occurrence of COPD in patients having respiratory allergic symptoms by routine spirometric screening. Five hundred and fifty urban patients aged 18-60 years (both gender) ailing from chronic respiratory symptoms like cough, wheeze and Shortness Of Breath (SOB), who were referred from OPDs of RGKMCH, Kolkata, were included in this study. After obtaining detailed clinical profile, patients were divided into two groups: subjects having additional clinical symptoms suggestive of respiratory allergy (n=260) like nasal catarrh, nasal stuffiness and sneezing and subjects with no symptoms suggestive of respiratory allergy (n=290). Thereafter, routine spirometry was carried out following recommendations of ATS/ERS (2005). Patients were then categorized based on FVC, FEV1, FEV1/FVC, FEF25-75 and PEFR percent predicted values. Study revealed that 18.97% of non-allergic population was suffering from COPD whereas only 7.69% of allergic subjects had COPD. This difference was statistically highly significant (p=0.0001). Although there was no significant difference in prevalence of respiratory symptoms between these two groups. Present study concludes that patients with respiratory allergy may have coexistent COPD but occurrence of COPD is much less than that in patients with no respiratory allergy.