Changes in Peak Inspiratory Flow After Acute Bronchodilation: An Observational Study of Patients with Stable Chronic Obstructive Pulmonary Disease.

Introduction: Identifying factors influencing peak inspiratory flow (PIF) is essential for aerosol drug delivery in stable patients with chronic obstructive pulmonary disease. While a minimum PIF for dry powder inhalers (DPIs) is established, acute bronchodilator (BD) effects on PIF remain unknown. Materials and Methods: An inspiratory flow meter (In-Check™ DIAL) was used to measure PIF in stable patients during a 24-week observational cross-sectional study. Additionally, bronchodilator responsiveness (BDR) was determined using the In-Check DIAL device and spirometry. Patients received four puffs of albuterol, and pre- and post-BD PIF, forced expiratory volume in one second (FEV1), and forced vital capacity were measured. Sixty-three patients completed acute BDR data collection from July 31, 2019, to November 9, 2021. Primary endpoints were pre- and post-BD spirometry and PIF. Statistical analyses included PIF correlations with FEV1. BD change was assessed according to inhaler resistance and sex (subgroup analysis). Results: Median patient age was 64.8 years, 85.7% were non-Hispanic White, and 57.1% were female. The median increase in absolute PIF (In-Check DIAL) was 5.0 L/min, and the % PIF change was 8.9%. With albuterol, 57.1% experienced a PIF BD change >5.0%, whereas 49.2% experienced a change >10.0%. Similarly, 55.6% experienced an FEV1 BD change >5.0% and 28.6% had a >10.0% FEV1 BD change with albuterol. PIF was weakly correlated with FEV1 BD change (absolute; % PIF; r = 0.28 [p = 0.02]; r = 0.21 [p = 0.11]). Pre- and post-BD median PIF were 75.5 and 83.5 L/min for low-to-medium-resistance DPI and 45.0 and 52.0 L/min for high-resistance, respectively. The median increases in pre- and post-BD PIF were 9.0 L/min in males and 4.5 L/min in females. In contrast to when using the In-Check DIAL device, we observed no consistent bronchodilatory effects on PIF measured by spirometry. Conclusions: Using the In-Check DIAL device, ∼50% of patients experienced >10% PIF increase after acute BD, potentially enhancing medication lung deposition. Further research is required to understand PIF's impact on medication delivery. ClinicalTrials.gov Identifier: NCT04168775.

A retrospective review of the rate of sexually transmitted infections in adolescents after universal screening protocol implementation in an urban United States clinic.

Objective: Despite expanded guidelines, adolescent gonorrhea and chlamydia (GC/CT) screening rates remain low due to multiple psychosocial barriers and biases. This intervention aimed to improve screening and diagnosis rates at adolescent well visits by establishing a streamlined universal screening protocol for all patients ages 13-18 years old. Methods: A universal sexually transmitted infection (STI) screening approach was introduced at an urban clinic affiliated with an academic medical center near Philadelphia, Pennsylvania (PA) in September 2018 for all adolescent well-visits. GC/CT screening and diagnosis rates were compared two years prior to and two years after implementation, deemed the baseline and intervention groups, respectively. Results: In total, 1,168 encounters were included for analysis. The patient cohort consisted of 47% females, with an average age of 15, and were predominantly publicly insured (79%). STI screening rates increased significantly from 16.7% (89/534) to 83.6% (530/634) of adolescents with implementation of the universal screening protocol. Furthermore, there was a 1.6-fold increase in total positive cases detected after implementation of ok universal screening. Conclusion: This study demonstrates improved adolescent GC/CT capture rates by establishing a universal screening protocol and highlights a streamlined means of implementation in virtually any pediatric clinic. Limitations include sample size, as this is a single academic practice, as well as any issues with lab collection and results reporting.

Effect on Physical Position of Peak Inspiratory Flow in Stable COPD: An Observational Study.

Background: We examined the effect of physical position on peak inspiratory flow (PIF) in patients with chronic obstructive pulmonary disease (COPD) using dry-powder inhalers (DPIs) with low­medium internal resistance (R2) and/or high internal resistance (R5). Methods: This prospective study in stable, ambulatory patients with spirometry-confirmed COPD evaluated the effect of 3 physical positions on maximal PIF achieved. Participants had PIFs of 30-90L/min (R5) or 60-90L/min (R2 DPIs) using the In-Check™ DIAL. PIF was measured in triplicate randomly in 3 positions that patients might be in while using their inhaler (standing, sitting, and semi-upright [supine position with the head of the bed at 45°, neck flexed forward]) against prescribed DPI resistance (R2/R5/both). Correlations between PIF and percentage decline in PIF between positions and differences in participant characteristics with >10% versus ≤10% PIF decline standing to semi-upright were calculated. Results: A total of 76 participants (mean age, 65.2 years) had positional measurements; 59% reported seated DPI use at home. The mean (standard deviation) PIF standing, sitting, and semi-upright was 80.7 (13.4), 77.8 (14.3), and 74.0 (14.5) L/min, respectively, for R2 and 51.1 (9.52), 48.6 (9.84), and 45.8 (7.69) L/min, respectively, for R5 DPIs. PIF semi-upright was significantly lower than sitting and standing (R2; P < 0.0001) and standing (R5; P= 0.002). Approximately half of the participants had >10% decline in PIF from standing to semi-upright. Patient characteristics exceeding the 0.10 absolute standardized difference threshold with the decline in PIF for both the R2 and R5 DPIs were waist-to-hip ratio, modified Medical Research Council dyspnea score, and postbronchodilator percentage predicted forced vital capacity and PIF by spirometry. Conclusions: PIF was significantly affected by physical position regardless of DPI resistance. PIF was highest when standing and lowest when semi-upright. We recommend that patients with COPD stand while using an R2 or R5 DPI. Where unfeasible, the position should be sitting rather than semi-upright. ClinicalTrials.gov identifier NCT04168775.

Benchmark datasets incorporating diverse tasks, sample sizes, material systems, and data heterogeneity for materials informatics.

Materials discovery via machine learning has become an increasingly popular method due to its ability to rapidly predict materials properties in a time-efficient and low-cost manner. However, one limitation in this field is the lack of benchmark datasets, particularly those that encompass the size, tasks, material systems, and data modalities present in the materials informatics literature. This makes it difficult to identify optimal machine learning model choices including algorithm, model architecture, data splitting, and data featurization for a given task. Here, we attempt to address this lack of benchmark datasets by assembling a unique repository of 50 different datasets for materials properties. The data contains both experimental and computational data, data suited for regression as well as classification, sizes ranging from 12 to 6354 samples, and materials systems spanning the diversity of materials research. Data were extracted from 16 publications. In addition to cleaning the data where necessary, each dataset was split into train, validation, and test splits. For datasets with more than 100 values, train-val-test splits were created, either with a 5-fold or 10-fold cross-validation method, depending on what each respective paper did in their studies. Datasets with less than 100 values had train-test splits created using the Leave-One-Out cross-validation method. These benchmark data can serve as a basis for a more diverse benchmark dataset in the future to further improve their effectiveness in the comparison of machine learning models.

Effect of hypertonic saline on mucociliary clearance and clinical outcomes in chronic bronchitis.

BACKGROUND: Mucus dehydration and impaired mucus clearance are common features of cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). In CF, inhaled hypertonic saline (HS) improves lung function and produces sustained increases in mucociliary clearance (MCC). We hypothesised that administration of HS (7% NaCl) twice daily for 2 weeks would improve clinical outcomes and produce sustained increases in MCC in COPD subjects with a chronic bronchitis (CB) phenotype. METHODS: Twenty-two CB subjects completed a double-blinded, crossover study comparing inhaled HS to a hypotonic control solution (0.12% saline) administered via nebuliser twice daily for 2 weeks. Treatment order was randomised. During each treatment period, symptoms and spirometry were measured. MCC was measured at baseline, shortly after initial study agent administration, and approximately 12 h after the final dose. RESULTS: HS was safe and well tolerated but overall produced no significant improvements in spirometry or patient-reported outcomes. CB subjects had slower baseline MCC than healthy subjects. The MCC rates over 60 min (Ave60Clr) in CB subjects following 2 weeks of HS were not different from 0.12% saline but were slower than baseline (Ave60Clr was 9.1±6.3% at baseline versus 5.3±6.9% after HS; p<0.05). Subgroup analyses determined that subjects with residual baseline central lung clearance (14 subjects) had improved spirometry and symptoms following treatment with HS, but not 0.12% saline, treatment. CONCLUSIONS: Inhaled HS appeared to be safe in a general CB population. A specific phenotypic subgroup may benefit from HS but requires additional study.

Phenotypic and physiological responses to salt exposure in Sorghum reveal diversity among domesticated landraces.

PREMISE: Soil salinity negatively impacts plant function, development, and yield. To overcome this impediment to agricultural productivity, variation in morphological and physiological response to salinity among genotypes of important crops should be explored. Sorghum bicolor is a staple crop that has adapted to a variety of environmental conditions and contains a significant amount of standing genetic diversity, making it an exemplary species to study variation in salinity tolerance. METHODS: Twenty-one diverse Sorghum accessions were treated with nonsaline water or 75 mM sodium chloride. Salinity tolerance was assessed via changes in biomass between control and salt-treated individuals. Accessions were first rank-ordered for salinity tolerance, and then individuals spanning a wide range of responses were analyzed for foliar proline and ion accumulation. Tolerance rankings were then overlaid on a neighbor-joining tree. RESULTS: We found that, while proline is often a good indicator of osmotic adjustment and is historically associated with increased salt tolerance in many species, proline accumulation in sorghum reflects a stress response injury rather than acclimation. When combining ion profiles with stress tolerance indices, the variation observed in tolerance was not a sole result of Na+ accumulation, but rather reflected accession-specific mechanisms. CONCLUSIONS: We identified significant variation in salinity tolerance among Sorghum accessions that may be a result of the domestication history of Sorghum. When we compared our results with known phylogenetic relationships within sorghum, the most parsimonious explanation for our findings is that salinity tolerance was acquired early during domestication and subsequently lost in accessions growing in areas varying in soil salinity.

Genome-Wide Identification and Analysis of Arabidopsis Sodium Proton Antiporter (NHX) and Human Sodium Proton Exchanger (NHE) Homologs in Sorghum bicolor.

Na⁺ transporters play an important role during salt stress and development. The present study is aimed at genome-wide identification, in silico analysis of sodium-proton antiporter (NHX) and sodium-proton exchanger (NHE)-type transporters in Sorghum bicolor and their expression patterns under varied abiotic stress conditions. In Sorghum, seven NHX and nine NHE homologs were identified. Amiloride (a known inhibitor of Na⁺/H⁺ exchanger activity) binding motif was noticed in both types of the transporters. Chromosome 2 was found to be a hotspot region with five sodium transporters. Phylogenetic analysis inferred six ortholog and three paralog groups. To gain an insight into functional divergence of SbNHX/NHE transporters, real-time gene expression was performed under salt, drought, heat, and cold stresses in embryo, root, stem, and leaf tissues. Expression patterns revealed that both SbNHXs and SbNHEs are responsive either to single or multiple abiotic stresses. The predicted protein⁻protein interaction networks revealed that only SbNHX7 is involved in the calcineurin B-like proteins (CBL)- CBL interacting protein kinases (CIPK) pathway. The study provides insights into the functional divergence of SbNHX/NHE transporter genes with tissue specific expressions in Sorghum under different abiotic stress conditions.

Mucus Hydration in Subjects with Stable Chronic Bronchitis: A Comparison of Spontaneous and Induced Sputum.

Mucus hydration is important in mucus clearance and lung health. This study sought to test the relative utility of spontaneous sputum (SS) versus the reasonably noninvasive induced sputum (IS) samples for measurement of mucus hydration. SS and IS samples were collected over a 2-day study interval. Sputum was induced with escalating inhaled nebulized 3-5% hypertonic saline. Viscous portions of the samples ("plugs") were utilized for percent solids and total mucin analyses. Cytokines, nucleotides/nucleosides and cell differentials were measured in plugs diluted into 0.1% Sputolysin. Overall, 61.5% of chronic bronchitis (CB) subjects produced a SS sample and 95.2% an IS sample. Total expectorate sample weights were less for the SS (0.94 ± 0.98 g) than the IS (2.67 ± 2.33 g) samples. Percent solids for the SS samples (3.56% ± 1.95; n = 162) were significantly greater than the IS samples (3.08% ± 1.81; n = 121), p = 0.133. Total mucin concentrations also exhibited a dilution of the IS samples: SS = 4.15 ± 3.23 mg/ml (n = 62) versus IS= 3.34 ± 2.55 mg/ml (n = 71) (p = 0.371). Total mucins (combined SS and IS) but not percent solids, were inversely associated with FEV1 percent predicted (p = 0.052) and FEV1,/FVC % (p = 0.035). There were no significant differences between sample types in cytokine or differential cell counts. The probability of sample collections was less for SS than IS samples. Measurements of hydration revealed modest dilution of the IS samples compared to SS. Thus for measurements of mucus hydration, both SS and IS samples appear to be largely interchangeable.

Airway Mucin Concentration as a Marker of Chronic Bronchitis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitic and emphysematous components. In one biophysical model, the concentration of mucin on the airway surfaces is hypothesized to be a key variable that controls mucus transport in healthy persons versus cessation of transport in persons with muco-obstructive lung diseases. Under this model, it is postulated that a high mucin concentration produces the sputum and disease progression that are characteristic of chronic bronchitis. METHODS: We characterized the COPD status of 917 participants from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) using questionnaires administered to participants, chest tomography, spirometry, and examination of induced sputum. Total mucin concentrations in sputum were measured with the use of size-exclusion chromatography and refractometry. In 148 of these participants, the respiratory secreted mucins MUC5AC and MUC5B were quantitated by means of mass spectrometry. Data from chronic-bronchitis questionnaires and data on total mucin concentrations in sputum were also analyzed in an independent 94-participant cohort. RESULTS: Mean (±SE) total mucin concentrations were higher in current or former smokers with severe COPD than in controls who had never smoked (3166±402 vs. 1515±152 µg per milliliter) and were higher in participants with two or more respiratory exacerbations per year than in those with zero exacerbations (4194±878 vs. 2458±113 µg per milliliter). The absolute concentrations of MUC5B and MUC5AC in current or former smokers with severe COPD were approximately 3 times as high and 10 times as high, respectively, as in controls who had never smoked. Receiver-operating-characteristic curve analysis of the association between total mucin concentration and a diagnosis of chronic bronchitis yielded areas under the curve of 0.72 (95% confidence interval [CI], 0.65 to 0.79) for the SPIROMICS cohort and 0.82 (95% CI, 0.73 to 0.92) for the independent cohort. CONCLUSIONS: Airway mucin concentrations may quantitate a key component of the chronic bronchitis pathophysiologic cascade that produces sputum and mediates disease severity. Studies designed to explore total mucin concentrations in sputum as a diagnostic biomarker and therapeutic target for chronic bronchitis appear to be warranted. (Funded by the National Heart, Lung, and Blood Institute and others.).

Interstital lung disease in ANCA vasculitis.

Anti-neutrophil cytoplasmic antibodies (ANCA) vasculitides are immune-mediated disorders that primarily affect small blood vessels of the airway and kidneys. Lung involvement, one of the hallmarks of microscopic polyangiitis and granulomatosis with polyangiitis, is associated with increased mortality and morbidity. In recent years, several retrospective series and case reports have described the association of interstitial lung disease (ILD) and ANCA vasculitis, particularly those positive for ANCA specific for myeloperoxidase. In the majority of these patients pulmonary fibrosis occurs concurrently or predates the diagnosis of ANCA vasculitis. More importantly, these studies have shown that ILD has an adverse impact on the long-term prognosis of ANCA vasculitis. This review focuses on the main clinical and radiologic features of pulmonary fibrosis associated with anti-neutrophil cytoplasmic antibodies. Major histopathology features, prognosis and therapeutic options are summarized.

Multicenter Validation of a Customizable Scoring Tool for Selection of Trainees for a Residency or Fellowship Program. The EAST-IST Study.

RATIONALE: Few data have been published regarding scoring tools for selection of postgraduate medical trainee candidates that have wide applicability. OBJECTIVES: The authors present a novel scoring tool developed to assist postgraduate programs in generating an institution-specific rank list derived from selected elements of the U.S. Electronic Residency Application System (ERAS) application. METHODS: The authors developed and validated an ERAS and interview day scoring tool at five pulmonary and critical care fellowship programs: the ERAS Application Scoring Tool-Interview Scoring Tool. This scoring tool was then tested for intrarater correlation versus subjective rankings of ERAS applications. The process for development of the tool was performed at four other institutions, and it was performed alongside and compared with the "traditional" ranking methods at the five programs and compared with the submitted National Residency Match Program rank list. RESULTS: The ERAS Application Scoring Tool correlated highly with subjective faculty rankings at the primary institution (average Spearman's r = 0.77). The ERAS Application Scoring Tool-Interview Scoring Tool method correlated well with traditional ranking methodology at all five institutions (Spearman's r = 0.54, 0.65, 0.72, 0.77, and 0.84). CONCLUSIONS: This study validates a process for selecting and weighting components of the ERAS application and interview day to create a customizable, institution-specific tool for ranking candidates to postgraduate medical education programs. This scoring system can be used in future studies to compare the outcomes of fellowship training.

Respiratory and Bronchitic Symptoms Predict Intention to Quit Smoking among Current Smokers with, and at Risk for, Chronic Obstructive Pulmonary Disease.

RATIONALE: Smoking cessation is the most important intervention for patients with chronic obstructive pulmonary disease (COPD). What leads smokers with COPD to quit smoking remains unknown. OBJECTIVES: We sought to examine the association between respiratory symptoms and other markers of COPD severity with intention to quit smoking among a cohort of patients with probable COPD. METHODS: We conducted a cross-sectional study of subjects with COPD or fixed airflow obstruction clinically diagnosed on the basis of pulmonary function testing. The subjects were identified in the COPD Outcomes-based Network for Clinical Effectiveness and Research Translation multicenter registry. The primary outcome was the intention to quit smoking within the next 30 days (yes or no), which was examined using model building with multivariable logistic regression, clustered by study site. MEASUREMENTS AND MAIN RESULTS: We identified 338 current smokers with COPD via the registry. Of these subjects, 57.4% (n = 194) had confirmed airflow obstruction based on pulmonary function testing. Nearly one-third (29.2%; n = 99) intended to quit smoking in the next 30 days. In adjusted analyses, compared with subjects without airflow obstruction based on pulmonary function testing, subjects with Global Initiative for Chronic Obstructive Lung Disease stage I/II COPD were more likely to be motivated to quit (odds ratio [OR], 1.85; 95% confidence interval [CI], 1.37-2.49), with no association found for subjects with Global Initiative for Chronic Obstructive Lung Disease stage III/IV disease. Among the entire cohort, frequent phlegm (OR, 2.10; 95% CI, 1.22-3.64), cough (OR, 1.74; 95% CI, 1.01-2.99), wheeze (OR, 1.73; 95% CI, 1.09-3.18), and higher modified Medical Research Council dyspnea score (OR, 1.26 per point; 95% CI, 1.13-1.41) were associated with increased odds of intending to quit smoking. Low self-reported health was associated with decreased odds of intending to quit (OR, 0.75; 95% CI, 0.62-0.92). CONCLUSIONS: Frequent cough, phlegm, wheeze, and shortness of breath were associated with intention to quit smoking in the next 30 days, with a less clear relationship for severity of illness graded by pulmonary function testing and self-rated health. These findings can be used to inform the content of tobacco cessation interventions to provide a more tailored approach for patients with respiratory diseases such as COPD.

Hydrator Therapies for Chronic Bronchitis. Lessons from Cystic Fibrosis.

Patients with the chronic bronchitis form of chronic obstructive pulmonary disease and cystic fibrosis share similar clinical features, including mucus obstruction of airways and the development of chronic/recurrent airways infections that often manifest as disease exacerbations. There is growing evidence that these diseases may have parallels in disease pathogenesis as well, including cystic fibrosis transmembrane conductance regulator dysfunction, mucus dehydration, and defective mucociliary clearance. As progress is made in the development of therapies that target the basic defects that lead to cystic fibrosis lung disease, it is possible that similar approaches could also benefit patients with chronic bronchitis. A deeper understanding of how tobacco smoke and other triggers of chronic bronchitis actually lead to disease, and exploration of the concept that therapies that restore cystic fibrosis transmembrane conductance regulator function, mucus hydration, and/or mucociliary clearance may benefit patients with chronic bronchitis, hold the prospect of significant progress in treating this prevalent disease.

Classifying Chronic Lower Respiratory Disease Events in Epidemiologic Cohort Studies.

RATIONALE: One in 12 adults has chronic obstructive pulmonary disease or asthma. Acute exacerbations of these chronic lower respiratory diseases (CLRDs) are a major cause of morbidity and mortality. Valid approaches to classifying cases and exacerbations in the general population are needed to facilitate prevention research. OBJECTIVES: To assess the feasibility, reproducibility, and performance of a protocol to identify CLRD cases and exacerbations triggering emergency department (ED) visits or hospitalizations in cohorts of patients derived from general populations of adults. METHODS: A protocol was developed to classify CLRD cases and severe exacerbations on the basis of review of medical records. ED and inpatient medical records were ascertained prospectively in the Hispanic Community Health Study/Study of Latinos, and inpatient records were retrospectively identified by administrative codes in the Multi-Ethnic Study of Atherosclerosis. "Probable" exacerbations were defined as a physician's diagnosis of CLRD with acute respiratory symptoms. "Highly probable" exacerbations additionally required systemic corticosteroid therapy, and "definite" exacerbations required airflow limitation or evidence of CLRD on imaging studies. Adjudicated results were compared with CLRD cases identified by spirometry and self-report, and with an administrative definition of exacerbations. MEASUREMENTS AND MAIN RESULTS: Protocol-based classification was completed independently by two physicians for 216 medical records (56 ED visits and 61 hospitalizations in the Hispanic Community Health Study/Study of Latinos; 99 hospitalizations in the Multi-Ethnic Study of Atherosclerosis). Reviewer disagreement occurred in 2-5% of cases and 4-8% of exacerbations. Eighty-nine percent of records were confirmed as at least probable CLRD cases. Fifty-six percent of confirmed CLRD cases had airflow limitation on the basis of baseline study spirometry. Of records that described CLRD as the primary discharge diagnosis code, an acute exacerbation was confirmed as at least probable for 96% and as highly probable or definite for 77%. Only 50% of records with CLRD as a secondary code were confirmed, although such records accounted for over half of all confirmed exacerbations. CONCLUSIONS: CLRD cases and severe exacerbations without preceding documentation of airflow limitation are identified frequently in population-based cohorts of persons. A primary discharge diagnosis of CLRD is specific but insensitive for defining exacerbations. Protocol-based classification of medical records may be appropriate to supplement and to validate identification of CLRD cases and exacerbations in general population studies. Clinical trials registered with www.clinicaltrials.gov (NCT00005487 and NCT02060344).

Pulmonary Disease and Age at Immigration among Hispanics. Results from the Hispanic Community Health Study/Study of Latinos.

RATIONALE: Asthma has been reported to be more prevalent among Hispanics of Puerto Rican heritage than among other Hispanics and among Hispanics born in the United States or who immigrated as children than among those who came as adults; however, direct comparisons across Hispanic groups are lacking. OBJECTIVES: To test whether asthma is more prevalent among Hispanics of Puerto Rican heritage than among other Hispanic groups, whether asthma is associated with age of immigration, and whether chronic obstructive pulmonary disease varies by heritage in a large, population-based cohort of Hispanics in the United States. METHODS: The Hispanic Community Health Study/Study of Latinos researchers recruited a population-based probability sample of 16,415 Hispanics/Latinos, 18-74 years of age, in New York City, Chicago, Miami, and San Diego. Participants self-reported Puerto Rican, Cuban, Dominican, Mexican, Central American, or South American heritage; birthplace; and, if relevant, age at immigration. A respiratory questionnaire and standardized spirometry were performed with post-bronchodilator measures for those with airflow limitation. MEASUREMENTS AND MAIN RESULTS: The prevalence of physician-diagnosed asthma among Puerto Ricans (36.5%; 95% confidence interval, 33.6-39.5%) was higher than among other Hispanics (odds ratio, 3.9; 95% confidence interval, 3.3-4.6). Hispanics who were born in the mainland United States or had immigrated as children had a higher asthma prevalence than those who had immigrated as adults (19.6, 19.4, and 14.1%, respectively; P < 0.001). Current asthma, bronchodilator responsiveness, and wheeze followed similar patterns. Chronic obstructive pulmonary disease prevalence was higher among Puerto Ricans (14.1%) and Cubans (9.8%) than among other Hispanics (<6.0%), but it did not vary across Hispanic heritages after adjustment for smoking and prior asthma (P = 0.22), by country of birth, or by age at immigration. CONCLUSIONS: Asthma was more prevalent among Puerto Ricans, other Hispanics born in the United States, and those who had immigrated as children than among other Hispanics. In contrast, the higher prevalence of chronic obstructive pulmonary disease among Puerto Ricans and Cubans was largely reflective of differential smoking patterns and asthma.

Phylogenetic reconstruction using four low-copy nuclear loci strongly supports a polyphyletic origin of the genus Sorghum.

BACKGROUND AND AIMS: Sorghum is an essential grain crop whose evolutionary placement within the Andropogoneae has been the subject of scrutiny for decades. Early studies using cytogenetic and morphological data point to a poly- or paraphyletic origin of the genus; however, acceptance of poly- or paraphyly has been met with resistance. This study aimed to address the species relationships within Sorghum, in addition to the placement of Sorghum within the tribe, using a phylogenetic approach and employing broad taxon sampling. METHODS: From 16 diverse Sorghum species, eight low-copy nuclear loci were sequenced that are known to play a role in morphological diversity and have been previously used to study evolutionary relationships in grasses. Further, the data for four of these loci were combined with those from 57 members of the Andropogoneae in order to determine the placement of Sorghum within the tribe. Both maximum likelihood and Bayesian analyses were performed on multilocus concatenated data matrices. KEY RESULTS: The Sorghum-specific topology provides strong support for two major lineages, in alignment with earlier studies employing chloroplast and internal transcribed spacer (ITS) markers. Clade I is composed of the Eu-, Chaeto- and Heterosorghum, while clade II contains the Stipo- and Parasorghum. When combined with data from the Andropogoneae, Clade II resolves as sister to a clade containing Miscanthus and Saccharum with high posterior probability and bootstrap support, and to the exclusion of Clade I. CONCLUSIONS: The results provide compelling evidence for a two-lineage polyphyletic ancestry of Sorghum within the larger Andropogoneae, i.e. the derivation of the two major Sorghum clades from a unique common ancestor. Rejection of monophyly in previous molecular studies is probably due to limited taxon sampling outside of the genus. The clade consisting of Para- and Stiposorghum resolves as sister to Miscanthus and Saccharum with strong node support.

The Relationship of Mucus Concentration (Hydration) to Mucus Osmotic Pressure and Transport in Chronic Bronchitis.

RATIONALE: Chronic bronchitis (CB) is characterized by persistent cough and sputum production. Studies were performed to test whether mucus hyperconcentration and increased partial osmotic pressure, in part caused by abnormal purine nucleotide regulation of ion transport, contribute to the pathogenesis of CB. OBJECTIVES: We tested the hypothesis that CB is characterized by mucus hyperconcentration, increased mucus partial osmotic pressures, and reduced mucus clearance. METHODS: We measured in subjects with CB as compared with normal and asymptomatic smoking control subjects indices of mucus concentration (hydration; i.e., percentage solids) and sputum adenine nucleotide/nucleoside concentrations. In addition, sputum partial osmotic pressures and mucus transport rates were measured in subjects with CB. MEASUREMENTS AND RESULTS: CB secretions were hyperconcentrated as indexed by an increase in percentage solids and total mucins, in part reflecting decreased extracellular nucleotide/nucleoside concentrations. CB mucus generated concentration-dependent increases in partial osmotic pressures into ranges predicted to reduce mucus transport. Mucociliary clearance (MCC) in subjects with CB was negatively correlated with mucus concentration (percentage solids). As a test of relationships between mucus concentration and disease, mucus concentrations and MCC were compared with FEV1, and both were significantly correlated. CONCLUSIONS: Abnormal regulation of airway surface hydration may slow MCC in CB and contribute to disease pathogenesis.

Metabolomic Evaluation of Neutrophilic Airway Inflammation in Cystic Fibrosis.

BACKGROUND: Metabolomic evaluation of cystic fibrosis (CF) airway secretions could identify metabolites and metabolic pathways involved in neutrophilic airway inflammation that could serve as biomarkers and therapeutic targets. METHODS: Mass spectrometry (MS)-based metabolomics was performed on a discovery set of BAL fluid samples from 25 children with CF, and targeted MS methods were used to identify and quantify metabolites related to neutrophilic inflammation. A biomarker panel of these metabolites was then compared with neutrophil counts and clinical markers in independent validation sets of lavage from children with CF and adults with COPD compared with control subjects. RESULTS: Of the 7,791 individual peaks detected by positive-mode MS metabolomics discovery profiling, 338 were associated with neutrophilic inflammation. Targeted MS determined that many of these peaks were generated by metabolites from pathways related to the metabolism of purines, polyamines, proteins, and nicotinamide. Analysis of the independent validation sets verified that, in subjects with CF or COPD, several metabolites, particularly those from purine metabolism and protein catabolism pathways, were strongly correlated with neutrophil counts and were related to clinical markers, including airway infection and lung function. CONCLUSIONS: MS metabolomics identified multiple metabolic pathways associated with neutrophilic airway inflammation. These findings provide insight into disease pathophysiology and can serve as the basis for developing disease biomarkers and therapeutic interventions for airways diseases.

Multicenter study comparing case definitions used to identify patients with chronic obstructive pulmonary disease.

RATIONALE: Clinical trials in chronic obstructive pulmonary disease (COPD) usually require evidence of airflow obstruction and clinical risk factors. International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes or patient-reported physician diagnoses are often used for epidemiologic studies and performance improvement programs. OBJECTIVES: To evaluate agreement between these case definitions for COPD and to assess the comparability of study populations identified as having COPD not using the clinical trial reference standard. METHODS: We recruited patients from the COPD Outcomes-based Network for Clinical Effectiveness and Research Translation multicenter clinical registry in a cross-sectional study. Demographics, clinical, and post-bronchodilator spirometry data were collected at an in-person study visit. The kappa statistic (κ) was used to evaluate agreement. A multivariable logistic regression model was used to identify patient characteristics associated with meeting the trial reference standard. MEASUREMENTS AND MAIN RESULTS: A total of 998 (82.8%) of 1,206 study participants met at least one case definition for COPD (of the 998: 91% using ICD-9 codes, 73% using patient-reported physician diagnosis, 56% using trial reference standard); agreement between case definitions was poor (κ = 0.20-0.26). Lack of airflow obstruction was the principal (89%) reason patients identified as having COPD did not meet the trial reference standard. Patients who were black (vs. white), obese (vs. normal weight), or had depression (vs. not) were less likely to meet the trial reference standard (odds ratio [95% CI], 0.37 [0.26-0.53], 0.51 [0.34-0.75], 0.53 [0.40-0.71], respectively). CONCLUSIONS: Findings highlight concerns about the applicability of findings in clinical trials to patients meeting other case definitions for COPD.

Measuring health-related quality of life in chronic obstructive pulmonary disease: properties of the EQ-5D-5L and PROMIS-43 short form.

BACKGROUND: The Patient Reported Outcomes Measurement Information System 43-item short form (PROMIS-43) and the five-level EQ-5D (EQ-5D-5L) are recently developed measures of health-related quality of life (HRQL) that have potentially broad application in evaluating treatments and capturing burden of respiratory-related diseases. The aims of this study were: (1) to examine their psychometric properties in patients with chronic obstructive pulmonary disease (COPD), and (2) to identify dimensions of HRQL that differ and do not differ by lung function. METHODS: We conducted a multi-center, cross-sectional study ("COPD Outcomes-based Network for Clinical Effectiveness & Research Translation" [CONCERT]). We analyzed patients who met spirometric criteria for COPD, and completed EQ-5D-5L and PROMIS questionnaires. Disease severity was graded based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. Pulmonary function test, PROMIS-43, EQ-5D (index score and EQ-Visual Analog Scale [EQ-VAS]), six minute walk test (6MWT), and three dyspnea scales (mMRC, Borg, FACIT-Dyspnea) were administered. Validity and reliability of EQ-5D-5L and PROMIS-43 were examined, and differences in HRQL by GOLD grade were assessed. RESULTS: Data from 670 patients with COPD were analyzed (mean age 68.5 years; 58% male). More severe COPD was associated with more problems with mobility, self-care and usual activities (all p-values <0.01) according to EQ-5D-5L. Related domains on EQ-5D-5L, PROMIS and clinical measures were moderately (r = 0.30-0.49) to strongly (r ≥ 0.50) correlated. A statistically significant trend of decreasing HRQL with more severe lung functions was observed for EQ-5D-5L index scores, EQ-VAS scores, and PROMIS physical function and social roles. CONCLUSIONS: Results supported the validity of EQ-5D-5L and PROMIS-43 in COPD patients, and indicate that physical function and social activities decrease with level of lung function by GOLD grade, but not pain, mental health, sleep or fatigue as reported by patients.