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Background: Relative enlargement of the pulmonary artery (PA) on chest CT imaging is associated with respiratory exacerbations in patients with COPD or cystic fibrosis. We sought to determine whether similar findings were present in patients with asthma and whether these findings were explained by differences in ventricular size.Methods: We measured the PA and aorta diameters in 233 individuals from the Severe Asthma Research Program III cohort. We also estimated right, left, and total epicardial cardiac ventricular volume indices (eERVVI, eELVVI, and eETVVI, respectively). Associations between the cardiac and PA measures (PA-to-aorta [PA/A] ratio, eERVVI-to-eELVVI [eRV/eLV] ratio, eERVVI, eELVVI, eETVVI) and clinical measures of asthma severity were assessed by Pearson correlation, and associations with asthma severity and exacerbation rate were evaluated by multivariable linear and zero-inflated negative binomial regression.Results: Asthma severity was associated with smaller ventricular volumes. For example, those with severe asthma had 36.1 mL/m2 smaller eETVVI than healthy control subjects (P = .003) and 14.1 mL/m2 smaller eETVVI than those with mild/moderate disease (P = .011). Smaller ventricular volumes were also associated with a higher rate of asthma exacerbations, both retrospectively and prospectively. For example, those with an eETVVI less than the median had a 57% higher rate of exacerbations during follow-up than those with eETVVI greater than the median (P = .020). Neither PA/A nor eRV/eLV was associated with asthma severity or exacerbations.Conclusions: In patients with asthma, smaller cardiac ventricular size may be associated with more severe disease and a higher rate of asthma exacerbations.Trial Registry: ClinicalTrials.gov; No.: NCT01761630; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Background: We designed an Internet-Based Monitoring Systems (IBS) survey to facilitate monitoring of asthma symptoms and asthma exacerbations in the Severe Asthma Research Program (SARP). Our objective was to evaluate compliance with the IBS survey tool and to explore how data from an IBS tool can inform understanding of asthma phenotypes.Methods: We invited adult subjects in the SARP III cohort (N = 528) to complete a monthly IBS asthma control survey. We compared the characteristics of subjects who did and those who did not participate in the IBS survey tool. Among subjects who participated in the IBS (IBS+), we identified participants with low, medium, and high Asthma Control Test (ACT) score variability, and we explored asthma morbidity in these three participant subgroups.Results: Two hundred fifty-nine subjects participated in the IBS (IBS+) survey. Compared with subjects who did not engage with the IBS (IBS-) survey, IBS+ subjects were older and more likely to be white, college educated, and have an annual household income > $25,000, and have controlled asthma. Among IBS+ participants, the subgroup with the highest ACT score variability was more likely to have severe asthma, with a lower ACT score at baseline and increased asthma-related health-care use (often precipitated by cold and flulike illnesses). Participants with high ACT variability were also characterized by metabolic dysfunction, as evidenced by obesity and hypertension.Conclusions: Active participation with an Internet-based symptom survey tool in patients with severe asthma is influenced by race, socioeconomic status, and asthma control. Among survey participants, a group with highly variable (labile) asthma control is identifiable as a specific subgroup with unmet treatment needs. The association of asthma lability, increased susceptibility to adverse asthma effects of cold and flulike illnesses, and metabolic dysfunction provides clues for potentially effective intervention strategies. [ABSTRACT FROM AUTHOR]

Background: Sleep difficulties are commonly reported by patients with asthma; however, the prevalence of insomnia and its association with disease burden and well-being is unknown. We aimed to determine the prevalence of insomnia, defined as combined sleep-specific complaints with associated daytime symptoms, among a large sample of adults with asthma, and to compare well-being, asthma control, and asthma-related health care utilization in individuals with asthma and insomnia and those without insomnia.Methods: Baseline data from adults with physician-confirmed asthma enrolled in the Severe Asthma Research Program III was used for analyses (N = 714). Participants completed the Insomnia Severity Index (ISI), Asthma Control Test, Asthma Quality of Life Questionnaire, and Hospital Anxiety and Depression Scale.Results: Insomnia (ISI ≥ 10) was identified in 263 participants (37%). Presence of insomnia was associated with higher levels of depression and anxiety symptoms and poorer quality of life. Those with insomnia had a 2.4-fold increased risk for having not well-controlled asthma and a 1.5-fold increased risk for asthma-related health care utilization in the past year compared with those without insomnia.Conclusions: Insomnia is highly prevalent in asthma and is associated with adverse outcomes. Further studies are needed to gain a better understanding of the interaction between insomnia and asthma control. [ABSTRACT FROM AUTHOR]

The article informs that the U.S. National Institute for Occupational Safety and Health recently reported on a microwave popcorn production plant where nine former workers showed severe fixed airways obstruction. Two of the former workers underwent biopsies and had findings compatible with bronchiolitis obliterans. Researchers measured airway inflammation by assessment of induced sputum obtained from workers in the microwave popcorn production plant. Induced sputum analysis is a reproducible, valid, and noninvasive method for studying airway inflammation. Use of induced sputum has been studied extensively in asthma and to a somewhat lesser degree in chronic obstructive pulmonary disease.

Study Objectives: To determine if persistent airway tissue mast cells are associated with treatment failure when patients discontinue inhaled corticosteroids (ICS).Design: Double-blind, randomized, placebo-controlled trial.Setting: Multicenter, tertiary referral centers.Patients or Participants: Forty-five subjects with asthma recruited from six medical centers in the United States.Interventions: The Asthma Clinical Research Network undertook a 28-week, randomized, multicenter, double-blind, placebo-controlled trial of 164 subjects with clinically stable, persistent asthma. A subset of subjects (n = 45) underwent bronchoscopy with endobronchial biopsy and BAL at the end of a 6-week run-in period, during which all subjects received triamcinolone acetonide (TAA), 400 microg bid. Airway tissue mast cells, eosinophils, neutrophils, macrophages, and T cells were quantified morphometrically along with determination of BAL tryptase. At the end of the run-in period, subjects were then randomized to receive salmeterol (42 micro g bid), placebo, or continue TAA for 16 weeks followed by a second bronchoscopy.Measurements and Results: Outcome variables included airway tissue mast cells, eosinophils, neutrophils, macrophages, and T cells that were quantified morphometrically and BAL tryptase. Thirty-five subjects completed the treatment phase; an additional 10 subjects, who were randomized to either salmeterol or placebo after the run-in, had treatment failure. When the bronchoscopy results performed at the end of the run-in, prior to randomization, were analyzed, the treatment failure group demonstrated significantly more tissue mast cells as compared to the nontreatment failure group despite 6 weeks of therapy with TAA (p = 0.04). BAL tryptase was also significantly higher in the treatment failure group (p < 0.0001). Of those subjects who completed the study, tissue mast cells and BAL tryptase did not change significantly within any of the treatment groups during the treatment phase (p > 0.05).Conclusions: Persistent elevations in airway tissue mast cells and BAL tryptase after treatment with TAA predict treatment failure in patients for whom discontinuation of ICS is being considered. [ABSTRACT FROM AUTHOR]

Goblet cell hyperplasia (GCH) has been established as a pathologic characteristic of mild, moderate, and severe asthma. Abnormalities in goblet cell number are accompanied by changes in stored and secreted mucin (MUC). The functional consequences of these changes in MUC stores and secretion can contribute to the pathophysiologic mechanisms for multiple clinical abnormalities in patients with asthma, including sputum production, airway narrowing, exacerbations, and accelerated loss in lung function. CD4[sup +] T cells and their T-helper type-2 cytokine products are important mediators of GCH, and MUC5AC is the dominant MUC gene that is expressed in goblet cells. The mechanism of cytokine-induced GCH, the relationships between MUC gene up-regulation and GCH, and the role of ion channels are all currently being explored. The process of working out the molecular mechanisms of GCH and goblet cell degranulation should provide new targets for novel therapeutic interventions. Such new treatments are urgently needed, because mucus hypersecretion is an important cause of morbidity and mortality in patients with asthma, and no specific treatments are available. [ABSTRACT FROM AUTHOR]

Study objectives: Several methods of utilizing peak expiratory flow (PEF) and other markers of disease activity have been suggested as useful in the management of asthma. It remains unclear, however, as to which surrogate markers of disease status are discriminative indicators of treatment failure, suitable for use in clinical trials. Design: We analyzed the operating characteristics of 66 surrogate markers of treatment failure using a receiver operating characteristic (ROC) curve analysis. Participants: Information regarding FEV[sub 1], symptoms, β[sub 2]-agonist use, and PEF was available from 313 subjects previously enrolled in two Asthma Clinical Research Network trials, in which 71 treatment failures occurred (defined by a 20% fall in FEV[sub 1] from baseline). Interventions: None. Measurements and results: None of the measures had an acceptable ability to discriminate subjects with a ≥20% fall in FEV[sub 1] from those without, regardless of the duration of the period of analysis or the criteria for test positivity employed. Areas under the ROC curves generated ranged from 0.51 to 0.79, but none were statistically superior. Sensitivity and specificity combinations were generally poor at all cutoff values; true-positive rates could not be raised without unacceptably elevating false-positive rates concurrently. Conclusions: Studies that seek to detect treatment failure defined by a significant fall in FEV[sub 1] should not use such individual surrogate measures to estimate disease severity. [ABSTRACT FROM AUTHOR]