Airflow Obstruction In Asthma Research Articles

The Diagnostic Performance of the FEF 25%-75% in the Evaluation of 34 Cases of Asthmatic Children and Adolescents Sensitized and Non-Sensitized to House Dust Mites

The guidelines for asthma and spirometry do not mention the forced expiratory flow between 25% and 75% of forced vital capacity (FEF 25%-75%) in evaluation of airflow obstruction in asthma. The aim of this study was to assess the diagnostic performance of the FEF 25%-75% of children and adolescents with asthma sensitized to house dust mites (HDM). A retrospective case series was done in the Hospital Municipal Jesus, Rio de Janeiro, Brazil with 34 participants with asthma sensitized (n=26) and non-sensitized (n=8) to HDM. Standard reference value for FEF 25%-75% was considered abnormal if below at 65% of predicted. The percentages of 62% of sensitized participants and 38% of not sensitized to HDM had asthma with small airway obstruction by FEF 25-75% index and normal reference values for large airway flow in the spirometry report according to FEV 1/FVC ratio. The means of FEF 25%-75% for HDM and non-HDM were 44.27±9.96 vs. 56.62±13.56, respectively (t=1.86, P=0.0719). The results calculated were a positive predictive value of 80%, a sensitivity of 65%, and an accuracy of 62% amongst other significant parameters (P<0.05). We concluded that the FEF 25%-75% had a high diagnostic performance in children and adolescents with asthma sensitized to HDM.

Fixed Airflow Obstruction in Asthma: A Problem of the Whole Lung Not of Just the Airways.

Asthma with irreversible or fixed airflow obstruction (FAO) is a severe clinical phenotype that is difficult to treat and is associated with an accelerated decline in lung function and excess morbidity. There are no current treatments to reverse or prevent this excessive decline in lung function in these patients, due to a lack of understanding of the underlying pathophysiology. The current paradigm is that FAO in asthma is due to airway remodeling driven by chronic inflammation. However, emerging evidence indicates significant and critical structural and functional changes to the lung parenchyma and its lung elastic properties in asthma with FAO, suggesting that FAO is a ‘whole lung’ problem and not just of the airways. In this Perspective we draw upon what is known thus far on the pathophysiological mechanisms contributing to FAO in asthma, and focus on recent advances and future directions. We propose the view that structural and functional changes in parenchymal tissue, are just as (if not more) important than airway remodeling in causing persistent lung function decline in asthma. We believe this paradigm of FAO should be considered when developing novel treatments.

Importance of the Functional Biomarker FEF 25%-75% in the Evaluation of Children and Adolescents with Asthma Sensibilized to House Dust Mites

Introduction: The GINA and the ATS do not mention that the forced expiratory flow between 25% and 75% of forced vital capacity (FEF 25%-75%) play importance in evaluation of airflow obstruction in asthma. Objectives: To investigate whether the evaluation of the FEF25%-75% in children and adolescents with asthma sensibilized to house dust mites (HDM) plays an important hole in airway obstruction from small airways. Methods. A retrospective study was done in Hospital Municipal Jesus (Rio de Janeiro, Brazil). Thirty-four children and adolescents with asthma were enrolled between January 2016 and December 2019. The FEIA (Immuno CAP®) was used to measure total and specific IgE antibodies to HDM. Standard reference value for small airways diseases with FEF 25%-75% was considered abnormal if below at 65% of predicted with FEV1/FVC ratio above or equal at 80%. Results. There was a significant difference between the mean ages of the sensitized (n=26; 9.8±2.53) and non-sensitized participants (n=8; 7.75±1.28) to HDM (P=0.0353). Male and female sexes were not significant in both groups (P=0.3698 and P=0.3298, respectively). If the FEF 25%-75% (L/s) was not valued in our study, 62% of sensitized participants (44.27±9.26) and 38% not sensitized (56.62±16.56) to HDM would be considered “according to normal reference values” (t=1.86; P=0.0719). Conclusions. The asthma in this study presented an obstructive respiratory disorder of small airways, regardless of a sensitization or a non-sensitization to HDM. The obstructive respiratory disorder of small airways was present, even with normal spirometry in the evaluation of large airways.

The Oral Eosinophil-lowering Drug Dexpramipexole Improves FEV1 Largely Thorough its Effect on FVC

Airflow obstruction in asthma (measured by FEV1) can be partitioned into components of air trapping in small airways (measured by FVC) and airway narrowing (measured by FEV1/FVC). Anti-eosinophil treatments improve lung function in asthma, but the effect of eosinophil depletion on individual components of airflow obstruction, i.e. FEV1/FVC vs FVC, are not established and may provide insight into the effects of eosinophils on pulmonary physiology.

Mucus Plugs Persist in Asthma, and Changes in Mucus Plugs Associate with Changes in Airflow over Time.

Rationale: Cross-sectional analysis of mucus plugs in computed tomography (CT) lung scans in the Severe Asthma Research Program (SARP)-3 showed a high mucus plug phenotype. Objectives: To determine if mucus plugs are a persistent asthma phenotype and if changes in mucus plugs over time associate with changes in lung function. Methods: In a longitudinal analysis of baseline and Year 3 CT lung scans in SARP-3 participants, radiologists generated mucus plug scores to assess mucus plug persistence over time. Changes in mucus plug score were analyzed in relation to changes in lung function and CT air trapping measures. Measurements and Main Results: In 164 participants, the mean (range) mucus plug score was similar at baseline and Year 3 (3.4 [0-20] vs. 3.8 [0-20]). Participants and bronchopulmonary segments with a baseline plug were more likely to have plugs at Year 3 than those without baseline plugs (risk ratio, 2.8; 95% confidence interval [CI], 2.0-4.1; P < 0.001; and risk ratio, 5.0; 95% CI, 4.5-5.6; P < 0.001, respectively). The change in mucus plug score from baseline to Year 3 was significantly negatively correlated with change in FEV1% predicted (rp = -0.35; P < 0.001) and with changes in CT air trapping measures (all P values < 0.05). Conclusions: Mucus plugs identify a persistent asthma phenotype, and susceptibility to mucus plugs occurs at the subject and the bronchopulmonary segment level. The association between change in mucus plug score and change in airflow over time supports a causal role for mucus plugs in mechanisms of airflow obstruction in asthma.

Mucus Plugs and Small Airway Dysfunction in Asthma, COPD, and Asthma-COPD Overlap.

PurposeThere are reports concerning mucus plugs detected on high-resolution computed tomography images and airflow obstruction in asthma and chronic obstructive pulmonary disease (COPD). However, little is known about the associations between mucus plugs and small airway dysfunction (SAD). We evaluated the relationship between mucus plugs and pulmonary function in patients with asthma, COPD, and asthma-COPD overlap (ACO), and investigated the relevance to SAD and type 2 inflammation in a retrospective study.MethodsSubjects included 49 asthmatic, 40 ACO, and 41 COPD patients. ACO was diagnosed based on the Japanese Respiratory Society ACO guidelines. Clinical and laboratory parameters, including blood eosinophil count, serum total IgE levels, fractional exhaled nitric oxide (FeNO), spirometry, and forced oscillation technique (FOT), were compared between patients with and without mucus plugs.ResultsMucus plugs were found in 29 (59%) asthmatic, 25 (65%) ACO, 17 (41%) COPD patients. Patients with mucus plugs had reduced spirometry and larger FOT parameters, especially in COPD patients. Mucus scores correlated positively with IgE in ACO and FeNO in asthmatic patients, but not in COPD patients. Multivariate logistic regression analysis revealed that SAD parameters, including forced vital capacity and resonant frequency, a respiratory reactance parameter, were significantly associated with the presence of mucus plugs in the whole studied population.ConclusionsSAD, rather than large airway dysfunction, was associated with mucus plugs in asthma, ACO, and COPD patients.

Inhibition of ABCC1 Decreases cAMP Egress and Promotes Human Airway Smooth Muscle Cell Relaxation.

In most living cells, the second-messenger roles for adenosine 3',5'-cyclic monophosphate (cAMP) are short-lived, confined to the intracellular space, and tightly controlled by the binary switch-like actions of Gαs (stimulatory G protein)-activated adenylyl cyclase (cAMP production) and cAMP-specific PDE (cAMP breakdown). Here, by using human airway smooth muscle (HASM) cells in culture as a model, we report that activation of the cell-surface β2AR (β2-adrenoceptor), a Gs-coupled GPCR (G protein-coupled receptor), evokes cAMP egress to the extracellular space. Increased extracellular cAMP levels ([cAMP]e) are long-lived in culture and are induced by receptor-dependent and receptor-independent mechanisms in such a way as to define a universal response class of increased intracellular cAMP levels ([cAMP]i). We find that HASM cells express multiple ATP-binding cassette (ABC) membrane transporters, with ABCC1 (ABC subfamily member C 1) being the most highly enriched transcript mapped to MRPs (multidrug resistance-associated proteins). We show that pharmacological inhibition or downregulation of ABCC1 with siRNA markedly reduces β2AR-evoked cAMP release from HASM cells. Furthermore, inhibition of ABCC1 activity or expression decreases basal tone and increases β-agonist-induced HASM cellular relaxation. These findings identify a previously unrecognized role for ABCC1 in the homeostatic regulation of [cAMP]i in HASM that may be conserved traits of the Gs-GPCRs (Gs-coupled family of GPCRs). Hence, the general features of this activation mechanism may uncover new disease-modifying targets in the treatment of airflow obstruction in asthma. Surprisingly, we find that serum cAMP levels are elevated in a small cohort of patients with asthma as compared with control subjects, which warrants further investigation.

Inflammatory patterns in fixed airflow obstruction are dependent on the presence of asthma.

Fixed airflow obstruction (FAO) can complicate asthma. Inflammation is a proposed underlying mechanism. Our aim in this cross-sectional investigation was to evaluate the blood leucocyte pattern and level of exhaled nitric oxide in asthmatics and non-asthmatics with or without FAO. A total of 11,579 individuals aged ≥20 years from the US National Health and Nutrition Examination Survey were included. They were grouped as: controls without asthma and FAO (n = 9,935), asthmatics without FAO (n = 674), asthmatics with FAO (n = 180) and non-asthmatics with FAO (n = 790). FAO was defined as post-bronchodilator FEV1/FVC < lower limit of normal. Exhaled nitric oxide ≥ 25ppb, blood eosinophil levels ≥300 cells/μL, and blood neutrophil levels ≥5100 cells/μL were defined as elevated. Stratified analyses for smoking and smoking history were performed. Elevated blood eosinophil levels were more common in all groups compared to the controls, with the highest prevalence in the group with asthma and fixed airflow obstruction (p<0.01). In a multiple logistic regression model adjusted for potential confounders including smoking, the asthma groups had significantly higher odds ratios for elevated B-Eos levels compared to the control group (odds ratio 1.4, (confidence interval: 1.1-1.7) for the asthma group without fixed airflow obstruction and 2.5 (1.4-4.2) for the asthma group with fixed airflow obstruction). The group with fixed airflow obstruction without asthma had higher odds ratio for elevated blood neutrophil levels compared to the controls: 1.4 (1.1-1.8). Smoking and a history of smoking were associated to elevated B-Neu levels. Fixed airflow obstruction in asthma was associated with elevated blood eosinophil levels, whereas fixed airflow obstruction without asthma was associated with elevated blood neutrophil levels.

UTILITY OF NOVEL FLOW VOLUME LOOP INDEXES IN DIAGNOSING AIRFLOW OBSTRUCTION

SESSION TITLE: Obstructive Lung Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Spirometry testing has a relatively low sensitivity for diagnosing airflow obstruction in asthma. Furthermore, it is known that patients with airflow obstruction tend to demonstrate coving on their flow-volume loops. Quantitative measurements of coving-related indices may perhaps improve our ability to diagnose airflow obstruction in asthma. Our study sought to compare the performance of established spirometric indices of obstruction with novel indices derived from flow volume loops using ROC analysis. To our knowledge, this is the first study to employ asthmatic patients with age and gender matched controls to compare the global performance of criteria for airflow obstruction. METHODS: This is a retrospective case-control study. Controls were obtained from another IRB-approved study (REVORE). In this study, normal subjects were selected based on responses to an in-depth questionaire asking about symptoms of asthma. Those who reported no symptoms underwent formal pulmonary function testing, including spirometry with bronchodilator challenge. For our study, we selected participants who had normal spirometry, lung volumes and diffusion capacity to act as controls. We then selected age- and gender-matched patients from an IRB-approved cohort (LUVA) of patients with asthma. As part of the LUVA study, all subjects had spirometry, lung volume and diffusion capacity measurements. Flow-volume loops were analyzed for cases and controls using a free online graphing software package (GeoGebra). Several measurements of each flow-volume loops were taken, includingthe distance from the point of peak expiratory flow to the point along the expiratory curve at which coving was most pronounced (point of maximal deflection, or PMD). ROC and AUC analyses were performed in SPSS version 25 to compare (1) PMD in cases versus controls, (2) magnitude of deflection at PMD in cases versus controls (MOD), and (3) FEV1/FVC ratio in cases versus controls. The ROC and AUC of the new indices were compared to those of FEV1/FVC ratio. RESULTS: 13 controls were matched to 20 cases. The male to female ratio was 7:6. Mean age, height and weight were similar between groups. The AUC for PMD was 0.876 (95%CI 0.740-1.011). At a cutoff of 0.715, the sensitivity and specificity were 76.9% and 92.3%, respectively. The AUC for MOD was 0.858 (95%CI 0.682-0.984). At a cutoff of 2.735, the sensitivity and specificity were 84.6% and 76.9%, respectively. AUC for FEV1/FVC ratio was 0.870 (95%CI 0.711-1.029). At a cutoff of 0.738, the sensitivity and specificity were 76.9 and 100%, respectively. CONCLUSIONS: PMD was the best overall criteria for diagnosing obstruction in asthma. These findings need confirmation in a larger cohort of asthmatics matched for gender and age. CLINICAL IMPLICATIONS: These indices may have the potential to improve our ability to identify patients who may benefit from asthma therapies. DISCLOSURES: No relevant relationships by Eric Day, source=Web Response No relevant relationships by Evanpaul Gill, source=Web Response no disclosure on file for Sneha Gullapalli; No relevant relationships by Viraj Jain, source=Web Response No relevant relationships by Kara Schmidt, source=Web Response no disclosure submitted for Jose Vempilly

Reduced lung elastic recoil and fixed airflow obstruction in asthma.

Fixed airflow obstruction (FAO) in asthma occurs despite optimal inhaled treatment and no smoking history, and remains a significant problem, particularly with increasing age and duration of asthma. Increased lung compliance and loss of lung elastic recoil has been observed in older people with asthma, but their link to FAO has not been established. We determined the relationship between abnormal lung elasticity and airflow obstruction in asthma. Non-smoking asthmatic subjects aged >40 years, treated with 2 months of high-dose inhaled corticosteroid/long-acting beta-agonist (ICS/LABA), had FAO measured by spirometry, and respiratory system resistance at 5 Hz (Rrs5 ) and respiratory system reactance at 5 Hz (Xrs5 ) measured by forced oscillation technique. Lung compliance (K) and elastic recoil (B/A) were calculated from pressure-volume curves measured by an oesophageal balloon. Linear correlations between K and B/A, and forced expiratory volume in 1 s/forced vital capacity (FEV1 /FVC), Rrs5 and Xrs5 were assessed. Eighteen subjects (11 males; mean ± SD age: 64 ± 8 years, asthma duration: 39 ± 22 years) had moderate FAO measured by spirometry ((mean ± SD z-score) post-bronchodilator FEV1 : -2.2 ± 0.5, FVC: -0.7 ± 1.0, FEV1 /FVC: -2.6 ± 0.7) and by increased Rrs5 (median (IQR) z-score) 2.7 (1.9 to 3.2) and decreased Xrs5 : -4.1(-2.4 to -7.3). Lung compliance (K) was increased in 9 of 18 subjects and lung elastic recoil (B/A) reduced in 5 of 18 subjects. FEV1 /FVC correlated negatively with K (rs = -0.60, P = 0.008) and Rrs5 correlated negatively with B/A (rs = -0.52, P = 0.026), independent of age. Xrs5 did not correlate with lung elasticity indices. Increased lung compliance and loss of elastic recoil relate to airflow obstruction in older non-smoking asthmatic subjects, independent of ageing. Thus, structural lung tissue changes may contribute to persistent, steroid-resistant airflow obstruction. ACTRN126150000985583 at anzctr.org.au (UTN: U1111-1156-2795).

High density lipoproteins and type 2 inflammatory biomarkers are negatively correlated in atopic asthmatics

Blood eosinophil counts and serum periostin levels are biomarkers of type 2 inflammation. Although serum levels of HDL and apoA-I have been associated with less severe airflow obstruction in asthma, it is not known whether serum lipids or lipoprotein particles are correlated with type 2 inflammation in asthmatics. Here, we assessed whether serum lipids and lipoproteins correlated with blood eosinophil counts or serum periostin levels in 165 atopic asthmatics and 163 nonasthmatic subjects with and without atopy. Serum lipids and lipoproteins were quantified using standard laboratory assays and NMR spectroscopy. Absolute blood eosinophils were quantified by complete blood counts. Periostin levels were measured using the Elecsys® periostin assay. In atopic asthmatics, blood eosinophils negatively correlated with serum HDL cholesterol and total HDL particles measured by NMR spectroscopy (HDLNMR). Serum periostin levels negatively correlated with total HDLNMR In contrast, blood eosinophil counts positively correlated with serum triglyceride levels. This study demonstrates for the first time that HDL particles were negatively correlated, whereas serum triglycerides were positively correlated, with blood eosinophils in atopic asthmatics. This supports the concept that serum levels of HDL and triglycerides may be linked to systemic type 2 inflammation in atopic asthma.

IL-17RB+ granulocytes are associated with airflow obstruction in asthma

BackgroundInterleukin (IL)-25 (IL-17E) is a proinflammatory cytokine that plays an important role in the T-helper type 2 cell pathway. The effects of IL-25 are mediated by its specific receptor, IL-17RB. Previous studies have defined an IL-17RB+ granulocyte population known as type 2 myeloid (T2M) cells that express T-helper type 2 cell cytokines. The correlation of IL-17RB+ granulocytes, T2M cells, and asthma parameters is unknown. ObjectiveTo investigate the relation of IL-17RB+ granulocytes (and its subset, T2M cells) in patients with asthma with clinical parameters including spirometric values and the Asthma Control Test (ACT). MethodsPeripheral blood from subjects with asthma and healthy controls was collected and analyzed by flow cytometry. Granulocytes were gated for IL-17RB+, T2M (CD11b+CD16+CD177+IL-17RB+), and eosinophil (CD16−) populations. Spirometry testing was performed on subjects with asthma. ACT scores and medical histories were collected by questionnaire and chart review. Correlations of IL-17RB+ cells and T2M cells with spirometry and ACT score were analyzed. ResultsPercentages of IL-17RB+ granulocytes and T2M cells were larger in subjects with asthma than in controls. Furthermore, percentages of the 2 cell populations were negatively correlated with degree of airway obstruction as measured by the ratio of percentage-predicted forced expiratory volume in 1 second to force vital capacity (r = −0.17, P = .043 for IL-17RB+ granulocytes; r = −0.32, P = .03 for T2M cells). There was no correlation with ACT score. The percentage of eosinophils was increased in subjects with asthma. However, IL-17RB+ eosinophil percentages were similar between subjects with asthma and controls and did not correlate with any clinical parameter. ConclusionIL-17RB+ granulocytes and T2M cells from peripheral blood were increased in subjects with asthma, and the 2 cell types correlated with degree of airflow obstruction.

Defining an olfactory receptor function in airway smooth muscle cells.

Pathways that control, or can be exploited to alter, the increase in airway smooth muscle (ASM) mass and cellular remodeling that occur in asthma are not well defined. Here we report the expression of odorant receptors (ORs) belonging to the superfamily of G-protein coupled receptors (GPCRs), as well as the canonical olfaction machinery (Golf and AC3) in the smooth muscle of human bronchi. In primary cultures of isolated human ASM, we identified mRNA expression for multiple ORs. Strikingly, OR51E2 was the most highly enriched OR transcript mapped to the human olfactome in lung-resident cells. In a heterologous expression system, OR51E2 trafficked readily to the cell surface and showed ligand selectivity and sensitivity to the short chain fatty acids (SCFAs) acetate and propionate. These endogenous metabolic byproducts of the gut microbiota slowed the rate of cytoskeletal remodeling, as well as the proliferation of human ASM cells. These cellular responses in vitro were found in ASM from non-asthmatics and asthmatics, and were absent in OR51E2-deleted primary human ASM. These results demonstrate a novel chemo-mechanical signaling network in the ASM and serve as a proof-of-concept that a specific receptor of the gut-lung axis can be targeted to treat airflow obstruction in asthma.

Improving Guideline-Based Care of Acute Asthma in a Pediatric Emergency Department.

Rapid repetitive administration of short-acting β-agonists (SABA) is the most effective means of reducing acute airflow obstruction in asthma. Little evidence exists that assesses process measures (ie, timeliness) and outcomes for asthma. We used quality improvement (QI) methods to improve emergency department care in accordance with national guidelines including timely SABA administration and use of asthma severity scores. The Model for Improvement was used and interventions were targeted at 4 key drivers: knowledge, engagement, decision support, and workflow enhancement. Time series analysis was performed and outcomes assessed on statistical process control charts. Asthma severity scoring increased from 0% to >95% in triage and to >75% for repeat scores. Time to first SABA (T1) improved by 32.8 minutes (47%). T1 for low severity patients improved by 17.6 minutes (28%). T1 for high severity patients improved by 3.1 minutes to 18.1 minutes (15%). Time to third SABA (T3) improved by 30 minutes (24%). T3 for low severity patients improved by 42.5 minutes (29%) and T3 for high severity patients improved by 21 minutes (23%). Emergency department length of stay for low severity patients discharged to home improved by 29.3 minutes (15%). The number of asthma-related visits between 48-hour return hospitalizations increased from 114 to 261. The admission rate decreased 6.0%. We implemented standardized asthma severity scoring with high rates of compliance, improved timely administration of β-agonist treatments, demonstrated early improvements in Emergency department length of stay, and reduced admission rates without increasing unplanned return admissions.

New Role of Adult Lung c-kit+ Cells in a Mouse Model of Airway Hyperresponsiveness.

Structural changes contribute to airway hyperresponsiveness and airflow obstruction in asthma. Emerging evidence points to the involvement of c-kit+ cells in lung homeostasis, although their potential role in asthma is unknown. Our aim was to isolate c-kit+ cells from normal mouse lungs and to test whether these cells can interfere with hallmarks of asthma in an animal model. Adult mouse GFP-tagged c-kit+ cells, intratracheally delivered in the ovalbumin-induced airway hyperresponsiveness, positively affected airway remodeling and improved airway function. In bronchoalveolar lavage fluid of cell-treated animals, a reduction in the number of inflammatory cells and in IL-4, IL-5, and IL-13 release, along with an increase of IL-10, was observed. In MSC-treated mice, the macrophage polarization to M2-like subset may explain, at least in part, the increment in the level of anti-inflammatory cytokine IL-10. After in vitro stimulation of c-kit+ cells with proinflammatory cytokines, the indoleamine 2,3-dioxygenase and TGFβ were upregulated. These data, together with the increased apoptosis of inflammatory cells in vivo, indicate that c-kit+ cells downregulate immune response in asthma by influencing local environment, possibly by cell-to-cell contact combined to paracrine action. In conclusion, intratracheally administered c-kit+ cells reduce inflammation, positively modulate airway remodeling, and improve function. These data document previously unrecognized properties of c-kit+ cells, able to impede pathophysiological features of experimental airway hyperresponsiveness.

LTC4 synthase polymorphism modifies efficacy of botanical seed oil combination in asthma.

Botanical seed oils reduce the generation of leukotrienes in patients with asthma.Our objective was to determine the efficacy of a botanical seed oil combination against airflow obstruction in asthma, and to determine the pharmacogenomic effect of the leukotriene C4 synthase (LTC4S) polymorphism A-444C.We conducted a randomized, double-blind, placebo-controlled, cross-over clinical trial in mild to moderate asthmatics to determine the change in FEV1 after 6 weeks of therapy with borage and echium seed oils versus corn oil placebo. We also examined the effect of the variant LTC4S -444C allele on the change in lung function.We did not identify a difference in FEV1 in the study cohort as a whole (n = 28), nor in the group of A homozygotes. In the C allele carriers (n = 9), FEV1 improved by 3% after treatment with borage and echium seed oils and declined by 4% after placebo corn oil (p = 0.02). All 9 C allele carriers demonstrated an improvement in their FEV1 on active treatment compared to placebo as compared to only 7 out of 19 A allele homozygotes (p = 0.007). We observed transient differences in ex vivo leukotriene generation from circulating basophils and granulocytes. We did not observe significant differences in urinary LTE4 levels.We conclude that compared to corn oil, a combination of borage and echium seed oils improves airflow obstruction in mild to moderate asthmatics who carry the variant allele in the LTC4S gene (A-444C). Botanical oil supplementation may have therapeutic potential in asthma if used in a personalized manner.Trial registration: This trial was registered at http://www.clinicaltrials.gov as NCT00806442.

Fixed airflow obstruction in asthma: a descriptive study of patient profiles and effect on treatment responses

Background: The role of fixed airflow obstruction (FAO) in asthma is unclear. Objective: To assess the relationship between FAO and clinical features of asthma and the effect of FAO on treatment response. Methods: Post hoc descriptive analysis of data stratified by FAO category (screening post-albuterol FEV1/FVC <lower limit of normal [LLN] [FAO+] or ≥LLN [FAO−]) from two 12-week, randomized, placebo-controlled studies of budesonide/formoterol or the monocomponents in mild−moderate (study I; aged ≥6 years; NCT00651651; placebo run-in) or moderate−severe (study II; ≥12 years; NCT00652002; budesonide run-in) asthma patients. Results: At baseline, FAO+ versus FAO− patients were more likely male and had longer asthma duration and worse pulmonary function. During the treatment period, lung function and asthma control measures with placebo were generally worse in FAO+ versus FAO− patients. Budesonide was effective on most end points in both FAO+ and FAO− patients. In contrast to FAO− patients, FAO+ patients were unresponsive to formoterol monotherapy in both study populations. Consistently greater improvements in most end points (including worsening of asthma as predefined by specific lung function parameters or clinical symptoms) were observed moving from formoterol to budesonide to budesonide/formoterol in both FAO+ and FAO− patients, with generally greater than additive effects on lung function with budesonide/formoterol in FAO+ patients. Conclusions: FAO+ patients tended to be more impaired and at greater risk for an asthma event versus FAO− patients. While FAO+ patients were non-responsive to formoterol monotherapy, they retained responsiveness to budesonide and had the greatest lung function and control responses to budesonide/formoterol that were similar to or greater than responses of FAO− patients.

Lung Volume Abnormalities and its Correlation to Spirometric and Demographic Variables in Adult Asthma

Background. Presence of airflow obstruction in asthma has been based on a fixed FEV1(forced expiratory volume at 1 second)/FVC (forced vital capacity) ratio abnormality. The accuracy of FEV1/FVC ratio in diagnosing airflow obstruction remains controversial. Lung volume abnormalities have been observed in severe asthma. We utilized simultaneously measured spirometry and lung volume to determine the utility of residual volume (RV)/total lung capacity (TLC) ratio in diagnosing airflow obstruction and to identify predictors of abnormal RV in asthmatic subjects. Methods. Data from physician-diagnosed asthmatics referred for lung function tests were collected retrospectively. Patient demographics and lung function data were analyzed using general linear modeling. Results. Of the 321 subjects, 221 were female (69%). The ethnicity was Caucasian in 157 (49%), Hispanic in 131 (41%), and African-American in 33 (10%). The percentage of subjects with FEV1/FVC ratio <70%, FEV1-predicted <80%, and FEF25–75% <65% were 25%, 25%, and 38%, respectively. Fifty-two and fifty-seven percent of the patients had abnormal residual volume and abnormal RV/TLC ratio, respectively. A significant bronchodilator response was observed in 32% of the patients. A positive correlation was observed between RV to age (r = 0.4) and height (r = 0.3). A negative correlation was observed between RV to FEF25–75% (r = 0.5) and body weight (r = 0.07). There was no significant correlation between FEV1 reversibility and residual volume (r = 0.1). RV correlated significantly better with FEF25–75% (r2 = 0.25) than FEV1 (r2 = 0.16). Conclusion. A significant proportion of asthmatic patients have elevated residual volume and abnormal RV/TLC ratio in the presence of normal FEV1/FVC ratio and absence of significant bronchodilator response. The clinical significance of these findings in asthma needs further prospective study.

Isolation of filamentous fungi from sputum in asthma is associated with reduced post-bronchodilator FEV1.

BackgroundFungal sensitization is common in severe asthma, but the clinical relevance of this and the relationship with airway colonization by fungi remain unclear. The range of fungi that may colonize the airways in asthma is unknown.ObjectiveTo provide a comprehensive analysis on the range of filamentous fungi isolated in sputum from people with asthma and report the relationship with their clinico-immunological features of their disease.MethodsWe recruited 126 subjects with a diagnosis of asthma, 94% with moderate-severe disease, and 18 healthy volunteers. At a single stable visit, subjects underwent spirometry; sputum fungal culture and a sputum cell differential count; skin prick testing to both common aeroallergens and an extended fungal panel; specific IgE to Aspergillus fumigatus. Fungi were identified by morphology and species identity was confirmed by sequencing. Four patients had allergic bronchopulmonary aspergillosis.ResultsForty-eight percent of asthma subjects were IgE-sensitized to one fungal allergen and 22% to ≥ 2. Twenty-seven different taxa of filamentous fungi were isolated from 54% of their sputa, more than one species being detected in 17%. This compared with 3 (17%) healthy controls culturing any fungus (P < 0.01). Aspergillus species were most frequently cultured in isolation followed by Penicillium species. Post-bronchodilator FEV1 (% predicted) in the subjects with asthma was 71(± 25) in those with a positive fungal culture vs. 83 (± 25) in those culture-negative, (P < 0.01).Conclusion and Clinical RelevanceNumerous thermotolerant fungi other than A. fumigatus can be cultured from sputum of people with moderate-to-severe asthma; a positive culture is associated with an impaired post-bronchodilator FEV1, which might be partly responsible for the development of fixed airflow obstruction in asthma. Sensitization to these fungi is also common.

Air trapping is a major determinant of persistent airway obstruction in asthmatics

Chronic persistent airway obstruction has been observed in moderate-to-severe asthmatics despite treatment with inhaled corticosteroids. We investigated which airway changes were associated with this obstruction. High-resolution computed tomography (HRCT) was performed at study entry and reexamined at the time of follow-up when the FEV1 reached a maximally constant level after treatment for 1 year or more with inhaled corticosteroids. Bronchial wall area and air trapping extent were compared in the recovered group (n = 18) and the persistent airway obstruction group (n = 14). Bronchial wall area and air trapping of the initial HRCT were similar between the two groups. On follow-up HRCT, air trapping was markedly decreased in the recovered group compared with that on initial HRCT (P = 0.017), whereas bronchial wall area did not change. In the persistent-airway-obstruction group, these two parameters did not change during follow-up. When follow-up HRCT was compared, air trapping was significantly greater in the persistent-airway-obstruction group than in the recovered group (P = 0.003). Difference post-bronchodilator FEV1 value between at initial and 2nd HRCT exam was correlated with difference air trapping value between at initial and 2nd HRCT exam(%) on the follow-up HRCT (P = 0.017). The presence of persistent airflow obstruction were significantly associated with the air trapping % difference between initial and 2nd time (RR = 1.70, P = 0.018). Persistence of AT could be a main contributing factor to chronic persistent airflow obstruction in asthma.