18 research outputs found
Corticosteroid treatment is associated with increased filamentous fungal burden in allergic fungal disease
Background
Allergic diseases caused by fungi are common. The best understood conditions are allergic
bronchopulmonaryaspergillosis (ABPA) and severe asthma with fungal sensitisation (SAFS).
Our knowledge of the fungal microbiome (mycobiome) is limited to a few studies involving
healthy individuals, asthmatics and smokers. No study has yet examined the mycobiome in
fungal lung disease.
Objectives
The main aim of this study was to determine the mycobiome in lungs of individuals with well
characterised fungal disease. A secondary objective was to determine possible effects of
treatment on the mycobiome.
Methods
After bronchoscopy, ITS1 DNA was amplified and sequenced and fungal load determined by
RT-PCR. Clinical and treatment variables were correlated with the main species identified.
ABPA (n=16), SAFS (n=16), severe asthma not sensitised to fungi, (n=9), mild asthma
patients(n=7) and 10 healthy controls were studied.
Results
The mycobiome was highly varied with severe asthmatics carrying higher loads of fungus.
Healthy individuals had low fungal loads, mostly poorly characterised Malasezziales.The
most common fungus in asthmatics was Aspergillus fumigatus complex and this taxon
accounted for the increased burden of fungus in the high level samples. Corticosteroid
treatment was significantly associated with increased fungal load (p<0.01).
Conclusions
The mycobiome is highly variable. Highest loads of fungus are observed in severe asthmatics
and the most common fungus is Aspergillus fumigatus complex. Individuals receiving steroid
therapy had significantly higher levels of Aspergillus and total fungus in their BAL
Role of regulatory T-cells in COPD
Chronic Obstructive Pulmonary Disease (COPD) is characterized by progressive and irreversible airflow limitation, caused in most cases by cigarette smoking. Increased CD8 cell numbers are associated with disease progression, and the presence of tertiary immune cell follicles in the lungs of COPD patients indicates a possible disease autoimmune component. T regulatory cells (Tregs) play an essential role in the control of adaptive immunity. This article reviews the current understanding of number and location of Tregs in lung compartments (airway lumen, parenchyma and follicles) in COPD patients. Treg lineages are detailed and their potential roles in COPD are considered. We discuss Treg function in COPD patients with a view to explaining the ongoing pulmonary inflammation despite Treg presence
CD4-regulatory cells in COPD patients
Background: The numbers of airway CD8 and B lymphocytes are increased in COPD patients, suggesting an autoimmune process. CD4-regulatory T cells control autoimmunity but have not been studied in patients with COPD.
Objective: To compare T-regulatory cell numbers in the BAL from COPD patients, smokers with normal lung function, and healthy nonsmokers (HNS).
Methods: BAL and peripheral blood mononuclear cell (PBMC) samples were obtained from 26 COPD patients, 19 smokers, and 8 HNS. Flow cytometry was performed for regulatory phenotypic markers.
Results: COPD patients had increased BAL CD8 numbers compared to smokers and HNS. CD4 numbers were similar between groups. There was increased BAL CD4CD25(bright) expression in smokers (median 28.8%) and COPD patients (median 23.1%) compared to HNS (median 0%). Increased FoxP3 expression was confirmed in BAL CD4CD25(bright) cells. BAL CD4CD25 cells expressed less CD27 compared to PBMCs, suggesting weaker functional regulatory ability.
Clinical implications: Chronic cigarette smoke exposure up-regulates airway CD4 regulatory cell numbers. Their function may be to control pulmonary inflammation
Reply to comment on chest-10-1440 : Increased airway T regulatory cells in asthmatic subjects
Assessment of the molecular basis of the proallergenic effects of cigarette smoke
Epidemiological studies indicate a link between smoking and increased risk of immunoglobulin E-mediated allergies and asthma. The molecular basis underlying cigarette smoke related respiratory disorders are ill defined, but it is known that mast cells in the mucosal lining of the airways are an important reservoir of proinflammatory mediators, which play a pivotal role in the development of these diseases. The establishment of a novel cell exposure unit facilitated a study of mast cell responses to pollutants in mainstream cigarette smoke at the air/cell interface. Our study shows that cigarette smoke, but not filtered clean air, induces the release of mediators of type I hypersensitivity responses and stimulates the synthesis of proinflammatory cytokines, including interleukin (IL)-4, 5, 10, and 13 and tumor necrosis factor (TNF)-α, in cells of mast cell lineage. These results explain how exposure to pollutants present in cigarette smoke can induce the pathophysiological responses associated with allergy, IgE-mediated and IgE-independent asthma since IL-4 and IL-13 induce class switching to IgE, and IL-13 has recently been identified as the key mediator of IgE-independent asthma
Identification of cells expressing Interleukin-17A and F in the lungs of COPD patients
Background: Lymphocytes secrete IL-17A and IL-17F which enhance innate immune responses. IL-17 expression has not been studied in COPD small airways. The aim was to quantify IL-17A and IL-17F expression in the peripheral lung tissue of COPD patients compared to controls and to identify inflammatory cells that express IL-17.
Methods: IL-17 expression was assessed using immunohistochemistry in peripheral lung tissue (18 COPD patients, 10 smokers and 10 non-smokers with normal lung function) and induced sputum (12 COPD patients and 6 non-smokers). Alveolar macrophages from 8 COPD patients, 8 smokers and 7 non-smokers were used for RT-PCR.
Results: The numbers of inflammatory cells expressing IL-17A in the small airway subepithelium was higher in COPD patients compared to smokers (p=0.01) and non-smokers (p=0.02). IL-17A expression was higher than IL-17F in this region. IL-17A was expressed by lymphocytes, neutrophils and macrophages (confirmed by RT-PCR). The expression of IL-17F was greater than IL-17A in epithelial cells and lymphoid follicles, although there were no differences between subject groups
Conclusion: Our findings indicate different roles for IL-17A and IL-17F in the pathogenesis of COPD; IL-17A plays a role in small airway subepithelial inflammation, while IL-17F appears to play a more prominent role within lymphoid follicles
The effects of corticosteroids on cytokine production from asthma lung lymphocytes
BACKGROUND
Lymphocytes play a central role in the pathophysiology of asthma. Corticosteroids have a limited effect in severe asthma and we hypothesise that lymphocytes play a central role in corticosteroid insensitivity. We investigated the effects of corticosteroids on cytokine production from lung lymphocytes obtained from patients with moderate severe asthma (MSA) compared to mild asthma (MA) and healthy non-smokers (HNS).
METHODS
Bronchoalveolar lavage (BAL) cells obtained by bronchoscopy from patients with MSA and MA (n = 11 and n = 14 respectively) and HNS (n = 7) were stimulated with CD2/3/28 beads to activate the lymphocytes, in the presence or absence of dexamethasone (0.01-1 μM). Supernatants were assayed for IL-2, IFNγ, IL-17, IL-13 and IL-10 production.
RESULTS
Dexamethasone caused variable inhibition of cytokines; 1 μM inhibited IL-10 and IL-17 by 50% or lower, while inhibition > 50% was observed for IL-2, IL-13 and IFNγ. The effect of dexamethasone on IL-13 production was reduced in MSA.
CONCLUSION
These findings suggest that the production of specific lymphocyte derived cytokines is poorly suppressed by corticosteroids in MSA, which may be responsible for persistent airway inflammation in these patient
Increased T-regulatory cells within lymphocyte follicles in moderate COPD
Lymphoid follicles in the lung parenchyma are a characteristic feature of chronic obstructive pulmonary disease (COPD). There are reports of altered CD4 T-regulatory cell numbers in COPD lungs, but the location of these cells within COPD lung tissue specific follicles has not been investigated.
The presence of CD4+FOXP3+ T-regulatory cells was assessed in surgically resected lung tissue from 12 COPD patients, 11 smokers with normal lung function and seven nonsmokers by combined immunofluorescence and immunohistochemistry.
Organised lymphoid follicles were observed in all three groups of patients, as well as lymphoid clusters lacking organisation. The percentage of CD4 cells that were T-regulatory cells were significantly increased (p = 0.02) within COPD (16%) follicles compared with smokers (10%) and nonsmokers (8%). In contrast, there was no change (p>0.05) in the percentage of T-regulatory cells in clusters or the subepithelium between groups.
Lymphoid follicles in COPD patients have increased T-regulatory cells. Therefore, T-regulatory activity may be altered within COPD lymphoid follicles