PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-16 (16)
 

Clipboard (0)
None

Select a Filter Below

Journals
Year of Publication
Document Types
1.  Lung clearance index in adults with non-cystic fibrosis bronchiectasis 
Respiratory Research  2014;15(1):59.
Background
Lung clearance index (LCI) is a measure of abnormal ventilation distribution derived from the multiple breath inert gas washout (MBW) technique. We aimed to determine the clinical utility of LCI in non-CF bronchiectasis, and to assess two novel MBW parameters that distinguish between increases in LCI due to specific ventilation inequality (LCIvent) and increased respiratory dead space (LCIds).
Methods
Forty-three patients with non-CF bronchiectasis and 18 healthy control subjects underwent MBW using the sulphur hexafluoride wash-in technique, and data from 40 adults with CF were re-analysed. LCIvent and LCIds were calculated using a theoretical two-compartment lung model, and represent the proportional increase in LCI above its ideal value due to specific ventilation inequality and increased respiratory dead space, respectively.
Results
LCI was significantly raised in patients with non-CF bronchiectasis compared to healthy controls (9.99 versus 7.28, p < 0.01), and discriminated well between these two groups (area under receiver operating curve = 0.90, versus 0.83 for forced expiratory volume in one second [% predicted]). LCI, LCIvent and LCIds were repeatable (intraclass correlation coefficient > 0.75), and correlated significantly with measures of spirometric airflow obstruction.
Conclusion
LCI is repeatable, discriminatory, and is associated with spirometric airflow obstruction in patients with non-CF bronchiectasis. LCIvent and LCIds are a practical and repeatable alternative to phase III slope analysis and may allow a further level of mechanistic information to be extracted from the MBW test in patients with severe ventilation heterogeneity.
doi:10.1186/1465-9921-15-59
PMCID: PMC4035904  PMID: 24884343
Bronchiectasis; Lung clearance index; Ventilation heterogeneity
2.  Fibrocyte localization to the airway smooth muscle is a feature of asthma 
Background
Airway smooth muscle (ASM) hyperplasia is a hallmark of asthma that is associated with disease severity and persistent airflow obstruction.
Objectives
We sought to investigate whether fibrocytes, a population of peripheral blood mesenchymal progenitors, are recruited to the ASM compartment in asthma.
Methods
We assessed the number of fibrocytes in bronchial biopsy specimens and peripheral blood from subjects with mild-to-severe refractory asthma versus healthy control subjects. In vitro we investigated potential mechanisms controlling fibrocyte migration toward the ASM bundle.
Results
Fifty-one subjects with asthma and 33 control subjects were studied. In bronchial biopsy specimens, the number of fibrocytes was increased in the lamina propria of subjects with severe refractory asthma (median [interquartile range] number, 1.9/mm2 [1.7/mm2]) versus healthy control subjects (median [interquartile range] number, 0/mm2 [0.3/mm2], P < .0001) and in the ASM bundle of subjects with asthma of all severities (subjects with severe asthma, median [interquartile range] number, 3.8/mm2 [9.4/mm2]; subjects with mild-to-moderate asthma, median [interquartile range] number, 1.1/mm2 [2.4/mm2]); healthy control subjects, (median [interquartile range] number, 0/mm2 [0/mm2]); P = .0004). In the peripheral blood the fibrocyte number was also increased in subjects with severe refractory asthma (median [interquartile range] number, 1.4 × 104/mL [2.6 × 104/mL]) versus healthy control subjects (median [interquartile range] number, 0.4 × 104/mL [1.0 × 104/mL], P = .002). We identified that in vitro ASM promotes fibrocyte chemotaxis and chemokinesis (distance of migration after 4.5 hours, 31 μm [2.9 μm] vs 17 μm [2.4 μm], P = .0001), which was in part mediated by platelet-derived growth factor (mean inhibition by neutralizing antibody, 16% [95% CI, 2% to 32%], P = .03) but not by activation of chemokine receptors.
Conclusion
This study provides the first evidence that fibrocytes are present in the ASM compartment in asthma and that ASM can augment fibrocyte migration. The importance of fibrocytes in the development of ASM hyperplasia and airway dysfunction in asthma remains to be determined.
doi:10.1016/j.jaci.2008.10.048
PMCID: PMC3992369  PMID: 19081612
Asthma; airway smooth muscle; remodeling; mast cells
3.  Eosinophil protein in airway macrophages: A novel biomarker of eosinophilic inflammation in patients with asthma 
Background
Noneosinophilic asthma is common across asthma severities. However, in patients with moderate-to-severe disease, the absence of sputum eosinophilia cannot distinguish between asthmatic subjects with eosinophilic inflammation controlled by corticosteroids versus those in whom eosinophilic inflammation is not a component of the disease.
Objectives
We sought to develop a method to quantify eosinophil proteins in airway macrophages as a novel biomarker of eosinophilic airway inflammation.
Methods
Eosinophil proteins in airway macrophages were assessed by means of flow cytometry, immunofluorescence, and cytoplasmic hue change after ingestion of apoptotic eosinophils. Airway macrophage median percentage of red-hued area in stained sputum cytospin preparations was assessed by means of image analysis from (1) subjects with mild-to-severe asthma, subjects with nonasthmatic eosinophilic bronchitis, and healthy control subjects; (2) subjects with eosinophilic severe asthma after treatment with prednisolone; and (3) subject with noneosinophilic asthma before corticosteroid withdrawal.
Results
Eosinophil proteins were detected in airway macrophages, and cytoplasmic red hue increased after ingestion of apoptotic eosinophils. Airway macrophage percentage red-hued area was increased in subjects with moderate-to-severe asthma compared with that seen in subjects with mild asthma and healthy control subjects, was similar in those with or without a sputum eosinophilia, and was increased after corticosteroid therapy. In asthmatic subjects without sputum eosinophilia, the airway macrophage percentage red-hued area was increased in subjects who did versus those who did not have sputum eosinophilia after corticosteroid withdrawal.
Conclusions
Eosinophil proteins can be reliably measured in airway macrophages. In combination with sputum eosinophilia, the macrophage eosinophil protein content might further define the asthma phenotype and provide an additional tool to direct therapy.
doi:10.1016/j.jaci.2010.03.026
PMCID: PMC3992372  PMID: 20639010
Asthma; macrophage; eosinophil; computer-assisted image analysis; induced sputum
4.  Airway hyperresponsiveness is dissociated from airway wall structural remodeling 
Background
Nonasthmatic eosinophilic bronchitis (EB) has emerged as a useful tool to study the structural and inflammatory mechanisms of airway hyperresponsiveness (AHR) in asthma. We have previously shown that vascular remodeling and reticular basement membrane (RBM) thickening are present in EB. However, it is not known whether other features of structural remodeling including increased airway smooth muscle (ASM) mass, matrix deposition, and glandular hyperplasia are also present in EB.
Objectives
We sought to determine whether structural remodeling occurs in EB and is associated with AHR and airflow limitation.
Methods
Forty-two patients with asthma, 21 patients with EB, and 19 healthy volunteers were recruited. ASM area, RBM thickness, collagen 3 deposition, glandular area, mast cells, and granulocytes were assessed in bronchial biopsy samples.
Results
Nonasthmatic eosinophilic bronchitis and asthma were associated with a significant increase in ASM mass and RBM thickness compared with healthy subjects. In contrast, we did not observe any significant differences in collagen 3 deposition in the lamina propria and ASM or the % area of glands in the lamina propria. Univariate analysis demonstrated that mast cell numbers in the ASM were the only feature of remodeling associated with AHR (β = −0.51; P = .004). Stepwise linear regression revealed that a combination of mast cell numbers in the ASM (β = −0.43) and disease duration (β = −0.25; model-adjusted R2 = 0.26; P = .027) best modeled AHR.
Conclusion
Mast cell localization to the ASM bundle, but not structural remodeling of the airway wall, is associated with AHR in asthma.
doi:10.1016/j.jaci.2008.05.020
PMCID: PMC3992373  PMID: 18572228
Asthma; nonasthmatic eosinophilic bronchitis; airway hyperresponsiveness; mast cell; remodeling
5.  Increased sputum and bronchial biopsy IL-13 expression in severe asthma 
Background
The importance of IL-13 in the asthma paradigm is supported by increased expression in human subjects, particularly in patients with mild-to-moderate asthma. However, the role of IL-13 in severe asthma needs to be further defined.
Objective
We sought to assess IL-13 expression in sputum and bronchial biopsy specimens from subjects with mild-to-severe asthma.
Methods
Sputum IL-13 concentrations were measured in 32 control subjects, 34 subjects with mild asthma, 21 subjects with moderate asthma, and 26 subjects with severe asthma. Enumeration of mast cells, eosinophils, and IL-13+ cells in the bronchial submucosa and airway smooth muscle (ASM) bundle was performed in 7 control subjects, 14 subjects with mild asthma, 7 subjects with moderate asthma, and 7 subjects with severe asthma.
Results
The proportion of subjects with measurable IL-13 in the sputum was increased in the mild asthma group (15/34) and severe asthma group (10/26) compared with that seen in the control group (4/32; P = .004). IL-13+ cells were increased within the submucosa in all asthma severity groups compared with control subjects (P = .006). The number of IL-13+ cells were increased within the ASM bundle in the severe asthma group compared with that seen in the other groups (P < .05). Asthma control questionnaire scores positively correlated with sputum IL-13 concentrations (Rs = 0.35, P = .04) and mast cells in the ASM bundle (Rs = 0.7, P = .007). IL-13+ cells within the submucosa and ASM correlated with sputum eosinophilia (Rs = 0.4, P ≤ .05).
Conclusions
IL-13 overexpression in sputum and bronchial biopsy specimens is a feature of severe asthma.
doi:10.1016/j.jaci.2008.01.005
PMCID: PMC3992379  PMID: 18328894
Severe asthma; IL-13; sputum; bronchus; airway smooth muscle; eosinophilia
6.  Mast Cells Promote Airway Smooth Muscle Cell Differentiation via Autocrine Up-Regulation of TGF-β11 
Asthma is a major cause of morbidity and mortality worldwide. It is characterized by airway dysfunction and inflammation. A key determinant of the asthma phenotype is infiltration of airway smooth muscle bundles by activated mast cells. We hypothesized that interactions between these cells promotes airway smooth muscle differentiation into a more contractile phenotype. In vitro coculture of human airway smooth muscle cells with β-tryptase, or mast cells with or without IgE/anti-IgE activation, increased airway smooth muscle-derived TGF-β1 secretion, α-smooth muscle actin expression and agonist-provoked contraction. This promotion to a more contractile phenotype was inhibited by both the serine protease inhibitor leupeptin and TGF-β1 neutralization, suggesting that the observed airway smooth muscle differentiation was driven by the autocrine release of TGF-β1 in response to activation by mast cell β-tryptase. Importantly, in vivo we found that in bronchial mucosal biopsies from asthmatics the intensity of α-smooth muscle actin expression was strongly related to the number of mast cells within or adjacent to an airway smooth muscle bundle. These findings suggest that mast cell localization in the airway smooth muscle bundle promotes airway smooth muscle cell differentiation into a more contractile phenotype, thus contributing to the disordered airway physiology that characterizes asthma.
PMCID: PMC3992381  PMID: 18802103
7.  Elevated Sputum Interleukin-5 and Submucosal Eosinophilia in Obese Individuals with Severe Asthma 
Rationale: The relationship between airway inflammation and obesity in severe asthma is poorly understood.
Objectives: We sought to determine the relationship between sputum mediator profiles and the distribution of eosinophilic inflammation and obesity in people with severe asthma.
Methods: Clinical parameters and eight mediators in sputum were assessed in 131 subjects with severe asthma from a single center categorized into lean, overweight, and obese groups defined by their body mass index. In an independent group of people with severe asthma (n = 45) and healthy control subjects (n = 19) eosinophilic inflammation was enumerated in bronchial submucosa, blood, and sputum and related to their body mass index.
Measurements and Main Results: Sputum IL-5 geometric mean (95% confidence interval) (pg/ml) was elevated in the obese (1.8 [1.2–2.6]) compared with overweight (1.1 [0.8–1.3]; P = 0.025) and lean (0.9 [0.6–1.2]; P = 0.018) subjects with asthma and was correlated with body mass index (r = 0.29; P < 0.001). There was no relationship among body mass index, the sputum cell count, or other sputum mediators. In the bronchoscopy group the submucosal eosinophil number in the subjects with asthma was correlated with body mass index (Spearman rank correlation, rs = 0.38; P = 0.013) and the median (interquartile range) number of submucosal eosinophils was increased in obese (19.4 [11.8–31.2]) (cells per square millimeter) versus lean subjects (8.2 [5.4–14.6]) (P = 0.006). There was no significant association between sputum or peripheral blood eosinophil counts and body mass index.
Conclusions: Sputum IL-5 and submucosal eosinophils, but not sputum eosinophils, are elevated in obese people with severe asthma. Whether specific antieosinophilic therapy is beneficial, or improved diet and lifestyle in obese asthma has antiinflammatory effects beyond weight reduction, requires further study.
doi:10.1164/rccm.201208-1470OC
PMCID: PMC3826183  PMID: 23590263
asthma; obesity; cytokines; phenotypes; eosinophil
8.  Quantitative computed tomography–derived clusters: Redefining airway remodeling in asthmatic patients☆ 
Background
Asthma heterogeneity is multidimensional and requires additional tools to unravel its complexity. Computed tomography (CT)–assessed proximal airway remodeling and air trapping in asthmatic patients might provide new insights into underlying disease mechanisms.
Objectives
The aim of this study was to explore novel, quantitative, CT-determined asthma phenotypes.
Methods
Sixty-five asthmatic patients and 30 healthy subjects underwent detailed clinical, physiologic characterization and quantitative CT analysis. Factor and cluster analysis techniques were used to determine 3 novel, quantitative, CT-based asthma phenotypes.
Results
Patients with severe and mild-to-moderate asthma demonstrated smaller mean right upper lobe apical segmental bronchus (RB1) lumen volume (LV) in comparison with healthy control subjects (272.3 mm3 [SD, 112.6 mm3], 259.0 mm3 [SD, 53.3 mm3], 366.4 mm3 [SD, 195.3 mm3], respectively; P = .007) but no difference in RB1 wall volume (WV). Air trapping measured based on mean lung density expiratory/inspiratory ratio was greater in patients with severe and mild-to-moderate asthma compared with that seen in healthy control subjects (0.861 [SD, 0.05)], 0.866 [SD, 0.07], and 0.830 [SD, 0.06], respectively; P = .04). The fractal dimension of the segmented airway tree was less in asthmatic patients compared with that seen in control subjects (P = .007). Three novel, quantitative, CT-based asthma clusters were identified, all of which demonstrated air trapping. Cluster 1 demonstrates increased RB1 WV and RB1 LV but decreased RB1 percentage WV. On the contrary, cluster 3 subjects have the smallest RB1 WV and LV values but the highest RB1 percentage WV values. There is a lack of proximal airway remodeling in cluster 2 subjects.
Conclusions
Quantitative CT analysis provides a new perspective in asthma phenotyping, which might prove useful in patient selection for novel therapies.
doi:10.1016/j.jaci.2013.09.039
PMCID: PMC3969578  PMID: 24238646
Asthma; airway remodeling; distal airway; CT; quantitative imaging; phenotypes; cluster analysis; fractal analysis; ATS, American Thoracic Society; BSA, Body surface area; CT, Computed tomography; Dav, Averaged fractal dimension; De, Most efficient cover fractal dimension; Dsc, Slope-corrected fractal dimension; Dsce, Slope-corrected most-efficient covering fractal dimension; FRC, Functional residual capacity; HU, Hounsfield units; ICC, Intraclass correlation coefficient; LA, Lumen area; LV, Lumen volume; MLD E/I, Mean lung density expiratory/inspiratory ratio; Pi10, Hypothetical airway with internal perimeter of 10 mm; Po20, Hypothetical airways with outer airway perimeter of 20 mm; RB1, Right upper lobe apical segmental bronchus; ROI, Region of interest; RV, Residual volume; TLC, Total lung capacity; VI, Voxel index; VI−850 E-I, VI−850 change on paired inspiratory and expiratory CT scan; VI−850/−950 E-I, Voxel index change of percent voxels between −950 and −850 HU on paired inspiratory and expiratory CT scan; WA, Wall area; WV, Wall volume
9.  Sputum mediator profiling and relationship to airway wall geometry imaging in severe asthma 
Respiratory Research  2013;14(1):17.
Background
Severe asthma is a heterogeneous disease and the relationship between airway inflammation and airway remodelling is poorly understood. We sought to define sputum mediator profiles in severe asthmatics categorised by CT-determined airway geometry and sputum differential cell counts.
Methods
In a single centre cross-sectional observational study we recruited 59 subjects with severe asthma that underwent sputum induction and thoracic CT. Quantitative CT analysis of the apical segment of the right upper lobe (RB1) was performed. Forty-one mediators in sputum samples were measured of which 21 mediators that were assessable in >50% of samples were included in the analyses.
Results
Independent of airway geometry, sputum MMP9 and IL-1β were elevated in those groups with a high sputum neutrophil count while sputum ICAM was elevated in those subjects with a low sputum neutrophil count. In contrast, sputum CCL11, IL-1α and fibrinogen were different in groups stratified by both sputum neutrophil count and airway geometry. Sputum CCL11 concentration was elevated in subjects with a low sputum neutrophil count and high luminal and total RB1 area, whereas sputum IL1α was increased in subjects with a high sputum neutrophil count and low total RB1 area. Sputum fibrinogen was elevated in those subjects with RB1 luminal narrowing and in those subjects with neutrophilic inflammation without luminal narrowing.
Conclusions
We have demonstrated that sputum mediator profiling reveals a number of associations with airway geometry. Whether these findings reflect important biological phenotypes that might inform stratified medicine approaches requires further investigation.
doi:10.1186/1465-9921-14-17
PMCID: PMC3577477  PMID: 23398985
Asthma; Remodelling; RB1 bronchus
10.  The Role of CT Scanning in Multidimensional Phenotyping of COPD 
Chest  2011;140(3):634-642.
Background:
COPD is a heterogeneous disease characterized by airflow obstruction and diagnosed by lung function. CT imaging is emerging as an important, noninvasive tool in phenotyping COPD. However, the use of CT imaging in defining the disease heterogeneity above lung function is not fully known.
Methods:
Seventy-five patients with COPD (58 men, 17 women) were studied with CT imaging and with measures of airway inflammation. Airway physiology and health status were also determined.
Results:
The presence of emphysema (EM), bronchiectasis (BE), and bronchial wall thickening (BWT) was found in 67%, 27%, and 27% of subjects, respectively. The presence of EM was associated with lower lung function (mean difference % FEV1, −20%; 95% CI, −28 to −11; P < .001). There was no difference in airway inflammation, exacerbation frequency, or bacterial load in patients with EM alone or with BE and/or BWT ± EM. The diffusing capacity of the lung for carbon monoxide/alveolar volume ratio was the most sensitive and specific parameter in identifying EM (area under the receiver operator characteristic curve, 0.87; 95% CI, 0.79-0.96). Physiologic cluster analysis identified three clusters, two of which were EM predominant and the third characterized by a heterogeneous combination of EM and BE.
Conclusions:
The application of CT imaging can be useful as a tool in the multidimensional approach to phenotyping patients with COPD.
doi:10.1378/chest.10-3007
PMCID: PMC3168858  PMID: 21454400
11.  Quantitative analysis of high-resolution computed tomography scans in severe asthma subphenotypes 
Thorax  2010;65(9):775-781.
Background
Severe asthma is a heterogeneous condition. Airway remodelling is a feature of severe asthma and can be determined by the assessment of high-resolution computed tomography (HRCT) scans. The aim of this study was to assess whether airway remodelling is restricted to specific subphenotypes of severe asthma.
Methods
A retrospective analysis was performed of HRCT scans from subjects who had attended a single-centre severe asthma clinic between 2003 and 2008. The right upper lobe apical segmental bronchus (RB1) dimensions were measured and the clinical and sputum inflammatory characteristics associated with RB1 geometry were assessed by univariate and multivariate regression analyses. Longitudinal sputum data were available and were described as area under the time curve (AUC). Comparisons were made in RB1 geometry across subjects in four subphenotypes determined by cluster analysis, smokers and non-smokers, and subjects with and without persistent airflow obstruction.
Results
Ninety-nine subjects with severe asthma and 16 healthy controls were recruited. In the subjects with severe asthma the RB1 percentage wall area (%WA) was increased (p=0.009) and lumen area (LA)/body surface area (BSA) was decreased (p=0.008) compared with controls but was not different across the four subphenotypes. Airway geometry was not different between smokers and non-smokers and RB1 %WA was increased in those with persistent airflow obstruction. RB1 %WA in severe asthma was best associated with airflow limitation and persistent neutrophilic airway inflammation (model R2=0.27, p=0.001).
Conclusions
Airway remodelling of proximal airways occurs in severe asthma and is associated with impaired lung function and neutrophilic airway inflammation.
doi:10.1136/thx.2010.136374
PMCID: PMC2975950  PMID: 20805170
Severe asthma; airway remodelling; computed tomography; airway inflammation; quantitative analysis; asthma phenotypes; cluster analysis; imaging/CT MRI etc
12.  Expression and activation of the oxytocin receptor in airway smooth muscle cells: Regulation by TNFα and IL-13 
Respiratory Research  2010;11(1):104.
Background
During pregnancy asthma may remain stable, improve or worsen. The factors underlying the deleterious effect of pregnancy on asthma remain unknown. Oxytocin is a neurohypophyseal protein that regulates a number of central and peripheral responses such as uterine contractions and milk ejection. Additional evidence suggests that oxytocin regulates inflammatory processes in other tissues given the ubiquitous expression of the oxytocin receptor. The purpose of this study was to define the role of oxytocin in modulating human airway smooth muscle (HASMCs) function in the presence and absence of IL-13 and TNFα, cytokines known to be important in asthma.
Method
Expression of oxytocin receptor in cultured HASMCs was performed by real time PCR and flow cytomery assays. Responses to oxytocin was assessed by fluorimetry to detect calcium signals while isolated tracheal rings and precision cut lung slices (PCLS) were used to measure contractile responses. Finally, ELISA was used to compare oxytocin levels in the bronchoalveloar lavage (BAL) samples from healthy subjects and those with asthma.
Results
PCR analysis demonstrates that OXTR is expressed in HASMCs under basal conditions and that both interleukin (IL)-13 and tumor necrosis factor (TNFα) stimulate a time-dependent increase in OXTR expression at 6 and 18 hr. Additionally, oxytocin increases cytosolic calcium levels in fura-2-loaded HASMCs that were enhanced in cells treated for 24 hr with IL-13. Interestingly, TNFα had little effect on oxytocin-induced calcium response despite increasing receptor expression. Using isolated murine tracheal rings and PCLS, oxytocin also promoted force generation and airway narrowing. Further, oxytocin levels are detectable in bronchoalveolar lavage (BAL) fluid derived from healthy subjects as well as from those with asthma.
Conclusion
Taken together, we show that cytokines modulate the expression of functional oxytocin receptors in HASMCs suggesting a potential role for inflammation-induced changes in oxytocin receptor signaling in the regulation of airway hyper-responsiveness in asthma.
doi:10.1186/1465-9921-11-104
PMCID: PMC2922094  PMID: 20670427
13.  Expression of the T Helper 17-Associated Cytokines IL-17A and IL-17F in Asthma and COPD 
Chest  2010;138(5):1140-1147.
Background:
Asthma and COPD are characterized by airway dysfunction and inflammation. Neutrophilic airway inflammation is a common feature of COPD and is recognized in asthma, particularly in severe disease. The T helper (Th) 17 cytokines IL-17A and IL-17F have been implicated in the development of neutrophilic airway inflammation, but their expression in asthma and COPD is uncertain.
Methods:
We assessed IL-17A and IL-17F expression in the bronchial submucosa from 30 subjects with asthma, 10 ex-smokers with mild to moderate COPD, and 27 nonsmoking and 14 smoking control subjects. Sputum IL-17 concentration was measured in 165 subjects with asthma and 27 with COPD.
Results:
The median (interquartile range) IL-17A cells/mm2 submucosa was increased in mild to moderate asthma (2.1 [2.4]) compared with healthy control subjects (0.4 [2.8]) but not in severe asthma (P = .04). In COPD, IL-17A+ cells/mm2 submucosa were increased (0.5 [3.7]) compared with nonsmoking control subjects (0 [0]) but not compared with smoking control subjects (P = .046). IL-17F+ cells/mm2 submucosa were increased in severe asthma (2.7 [3.6]) and mild to moderate asthma (1.6 [1.0]) compared with healthy controls subjects (0.7 [1.4]) (P = .001) but was not increased in subjects with COPD. IL-17A and IL-17F were not associated with increased neutrophilic inflammation, but IL-17F was correlated with the submucosal eosinophil count (rs = 0.5, P = .005). The sputum IL-17 concentration in COPD was increased compared with asthma (2 [0-7] pg/mL vs 0 [0-2] pg/mL, P < .0001) and was correlated with post-bronchodilator FEV1% predicted (r = −0.5, P = .008) and FEV1/FVC (r = −0.4, P = .04).
Conclusions:
Our findings support a potential role for the Th17 cytokines IL-17A and IL-17F in asthma and COPD, but do not demonstrate a relationship with neutrophilic inflammation.
doi:10.1378/chest.09-3058
PMCID: PMC2972626  PMID: 20538817
14.  Airway Wall Expression of OX40/OX40L and Interleukin-4 in Asthma 
Chest  2010;137(4):797-804.
Background:
The costimulatory molecule OX40 and its ligand, OX40L, mediate key aspects of allergic airway inflammation in animal models of asthma, including eosinophilic airway inflammation, airway hyperresponsiveness, and T helper 2 polarization. We sought to examine OX40/OX40L and interleukin (IL)-4 expression in asthma across severities.
Methods:
Bronchial biopsies were obtained from 27 subjects with asthma (mild Global Initiative for Asthma [GINA] 1 [n = 10], moderate GINA 2-3 [n = 7], and severe GINA 4-5 [n = 10]) and 13 healthy controls. The number of OX40+, OX40L+, IL-4+, and IL-4 receptor α (IL-4Rα)+ cells in the lamina propria and airway smooth muscle (ASM) bundle and the intensity of IL-4Rα+ expression by the ASM were assessed.
Results:
The number of OX40+, OX40L+, and IL-4+ cells in the lamina propria and OX40+ and IL-4+ cells in the ASM bundle was significantly increased in subjects with mild asthma, but not in those with moderate or severe asthma, compared with healthy controls. In the subjects with asthma, OX40/OX40L expression was positively correlated with the number of eosinophils and IL-4+ cells in the lamina propria. The number of IL-4Rα+ cells in the lamina propria was significantly increased in moderate-to-severe disease, but not in mild asthma, compared with controls. IL-4Rα expression by the ASM bundle was not different among groups.
Conclusions:
OX40/OX40L expression is increased in the bronchial submucosa in mild asthma, but not in moderate-to-severe disease, and is related to the degree of tissue eosinophilia and IL-4 expression. Whether these costimulatory molecules have a role as targets for asthma requires further investigation.
doi:10.1378/chest.09-1839
PMCID: PMC2851558  PMID: 20139223
15.  IL-13 expression by blood T cells and not eosinophils is increased in asthma compared to non-asthmatic eosinophilic bronchitis 
Background
In asthma interleukin (IL)-13 is increased in the airway compared with non-asthmatic eosinophilic bronchitis. Whether this differential expression is specific to the airway or is more generalised is uncertain.
Methods
We sought to examine IL-13 expression in peripheral blood T-cells and eosinophils in asthma and non-asthmatic eosinophilic bronchitis. Peripheral blood CD3+ cell and eosinophil intracellular IL-13 expression from subjects with asthma, non-asthmatic eosinophilic bronchitis and healthy controls was assessed. The effect of priming by asthmatic serum on the release of IL-13 by peripheral blood mononuclear cells from healthy subjects was examined and the serum from these subjects was analysed for a range of chemokines and cytokines.
Results
The median (IQR)% intracellular IL-13 expression by CD3+ cells was increased in asthma [5.3 (2.7–9.8)%; n = 12] compared to non-asthmatic eosinophilic bronchitis [1.1 (0.5–3)%; n = 7] and healthy controls [1.7 (0.2–3%); n = 9] (p = 0.02), but was not significantly different in eosinophils across the groups. IL-13 released from healthy peripheral blood mononuclear cells (n = 10) was increased by asthmatic serum [117 (47.8–198)pg/ml] compared to control [78.5 (42.6–128)pg/ml; p = 0.02), but was not affected by non-asthmatic serum.
Conclusion
Our findings support the view that IL-13 expression is increased in peripheral blood-derived T cells in asthma and that asthmatic serum up-regulates IL-13 release from healthy peripheral blood mononuclear cells.
doi:10.1186/1471-2466-9-34
PMCID: PMC2716303  PMID: 19602238
16.  Airways Disease: Phenotyping Heterogeneity Using Measures of Airway Inflammation 
Despite asthma and chronic obstructive pulmonary disease being widely regarded as heterogeneous diseases, a consensus for an accurate system of classification has not been agreed. Recent studies have suggested that the recognition of subphenotypes of airway disease based on the pattern of airway inflammation may be particularly useful in increasing our understanding of the disease. The use of non-invasive markers of airway inflammation has suggested the presence of four distinct phenotypes: eosinophilic, neutrophilic, mixed inflammatory and paucigranulocytic asthma. Recent studies suggest that these subgroups may differ in their etiology, immunopathology and response to treatment. Importantly, novel treatment approaches targeted at specific patterns of airway inflammation are emerging, making an appreciation of subphenotypes particularly relevant. New developments in phenotyping inflammation and other facets of airway disease mean that we are entering an era where careful phenotyping will lead to targeted therapy.
doi:10.1186/1710-1492-3-2-60
PMCID: PMC2873624  PMID: 20525145
asthma; COPD; eosinophil; inflammation; neutrophil

Results 1-16 (16)