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Biomedical subjects

C M Burke

Publications and source records attributed to C M Burke.

At least 19 recordsLinked to original sources
PubMed2004

Fluticasone induces T cell apoptosis in the bronchial wall of mild to moderate asthmatics.

BACKGROUND: Cytokines which signal via the gamma chain of the interleukin (IL)-2 receptor and the interferons (IFNs) have been shown to enhance T cell survival in vitro by rescuing cells from apoptosis. METHODS: A study was undertaken to determine whether treatment with inhaled fluticasone propionate (FP; 250 microg twice daily) for 2 weeks could modulate production of IL-15 or IFN-beta and thereby affect T cell survival in bronchial tissue of 10 patients with mild/moderate asthma. Bronchial biopsy specimens were taken before and on completion of treatment. RESULTS: The mean (95% CI) number of T cells per unit area decreased in the asthmatic group following 2 weeks of treatment with FP (from 7.0 (5.6 to 8.4) to 4.5 (4.0 to 5.1); p = 0.001). There was an increase in the percentage of T cells undergoing apoptosis following FP treatment as assessed by T cell/TUNEL staining (from 4.5 (2.6 to 6.4) to 8.7 (6.6 to 10.8); p = 0.0001). The percentage of cells staining for IL-15 and IFN-beta in the lamina propria, determined by an alkaline phosphatase biotin streptavidin technique, decreased significantly from baseline values of 31.6 (23.4 to 39.7) to 19.6 (12.5 to 26.7), p = 0.039 for IL-15 and from 18.9 (13.5 to 24.4) to 9.5 (5.9 to 13.1), p = 0.007 for IFN-beta following 2 weeks of treatment with FP. However, only the decrease in the percentage of cells staining for IL-15 was significantly correlated with an increased number of apoptotic T cells following treatment (p = 0.008). CONCLUSION: These findings support a novel mechanism for the ability of inhaled corticosteroids to decrease T cell numbers, possibly by downregulation of the cytokine IL-15.

Administration, Inhalation↗
PubMed2003

Release of inflammatory mediators from eosinophils following a hyperosmolar stimulus.

Airway dehydration and subsequent hyperosmolarity of periciliary fluid are considered critical events in exercise-induced bronchoconstriction (EIB). It has been shown that an in vitro hyperosmolar stimulation of basophils and mast cells with mannitol can induce the release of histamine and leukotrienes. The aim of this study was to establish if a hyperosmolar challenge could trigger activation of eosinophils to release chemokines and lipid mediators. Peripheral blood eosinophils were isolated from seven asthmatic and six non-asthmatic subjects. Hyperosmolar stimulation of eosinophils with mannitol (0.7 M), resulted in a significant increase in LTC4 levels compared to baseline in both asthmatic (15.2+/-4.6 vs. 70.1+/-9.5; P = 0.0002) and control subjects (14.3+/-4.0 vs. 55.6+/-5.6; P = 0.0001). ECP levels did not increase significantly above baseline following mannitol stimulation in either group. This study shows that eosinophils can be activated by a hyperosmolar stimulus. Therefore it seems reasonable to suggest that eosinophils could contribute to EIB.

Adolescent↗
PubMed2002

A case of frog breathing.

Frog breathing (glossopharyngeal breathing) is a useful technique employed to increase ventilation when respiratory muscles are paralysed. It is a technique used by many patients with chronic poliomyelitis, yet many chest physicians and physiotherapists are unfamiliar with this breathing maneuver. Glossopharyngeal breathing coordinates movements of the tongue, cheeks and pharynx to force air from the mouth into the lungs. We report a case of glossopharyngeal breathing, demonstrating a 3 fold increase in vital capacity in a subject with chronic poliomyelitis.

Humans↗
PubMed2001

Activated, cytotoxic CD8(+) T lymphocytes contribute to the pathology of asthma death.

This study investigates the presence of CD8(+) T lymphocytes and their possible association with viral infection in bronchi of victims of fatal asthma. Postmortem samples from the peribronchial region of the lung were obtained from seven patients who died an asthma death (AD), seven asthmatic patients who died of unrelated causes (AUC), and seven postmortem cases with no history of lung disease (control subjects). Using immunohistochemical techniques, the CD8(+) cytotoxic T-cell population in peribronchial tissue was characterized in three patient groups. The percentage of CD8(+) cells expressing the activation marker CD25 was higher in the AD group than in both the AUC and control groups (11.91 +/- 1.92% versus 3.93 +/- 1.63% and 1.09 +/- 0.56%, respectively (p < 0.001). Perforin expression, a marker of cytotoxicity, was highest in the AD group (9.16 +/- 1.5%) compared with 1.39 +/- 0.9; 1.8 +/- 0.6% in the AUC and control groups respectively (p < 0.001). Expression of interleukin-4 (IL-4) and interferon gamma (IFN-gamma) by CD8(+) T cells was higher in the AD group than the control group (p < 0.05). Furthermore, the IFN-gamma/IL-4 ratio in the AD group was less than half that of the control group (1.46 +/- 0.2 versus 3.2 +/- 0.1; p = 0.02). Using polymerase chain reaction (PCR), viral genome for rhinovirus (RV) was detected in lung tissue from three of the seven cases in the AD group. Two of these cases also had detectable respiratory syncytial virus (RSV). Viral genome for RSV was detected in five of the AUC group and in one of these cases, RV was also detected. No viral genome was detected in the lungs of the control group. In conclusion, this study provides novel evidence of an aberrant CD8(+) T-cell population, possibly in response to viral infection in subjects who die of acute asthma.

Acute Disease↗
PubMed2001

Isolation and partial characterisation of immunoglobulin from southern bluefin tuna Thunnus maccoyii Castelnau.

Specific and total serum immunoglobulins were extracted by immunoaffinity, mannan-binding protein and Protein A affinity chromatography from southern bluefin tuna (Thunnus maccoyii Castelnau) immunised with rabbit IgG, and from non-immunised southern bluefin tuna. SDS-PAGE in 10% reducing gels revealed two heavy chains with molecular weights of approximately 74.6 +/- 1.3 kDa and 71.2 +/- 0.9 kDa, and two light chains with molecular weights of approximately 29 +/- 1.2 kDa and 28 +/- 1.0 kDa. Under non-reducing, but denaturing, conditions in 4% and 5% SDS-PAGE gels, a high molecular weight and a low molecular weight fraction were demonstrated. By gel filtration using Sephacryl HR 300 a molecular weight of 845 kDa, consistent with a tetramer, was obtained for the high molecular weight fraction, and a molecular weight of 168 kDa, consistent with a monomer, was obtained for the low molecular weight fraction. The extinction coefficient at A280 for the purified immunoglobulin (Ig) was determined to be 1.24. Tuna a-rabbit IgG Ig was reactive with all non-reduced mammalian IgG antigens tested, suggesting that common conformational antigenic determinants were recognised.

Animals↗
PubMed2001

IFN-gamma but not IL-4 T cells of the asthmatic bronchial wall show increased incidence of apoptosis.

BACKGROUND: Previous observations have established that IFN-gamma production is depressed in CD4+ T cells from atopic asthmatics compared with non-asthmatics. OBJECTIVE: The aim of this study was to determine if decreased IFN-gamma production could be due to a dissociation between levels of apoptosis within the T cell subsets of the asthmatic bronchial wall. METHODS: Twenty asthmatics (10 atopic and 10 non-atopic) and eight non-atopic non-asthmatics underwent bronchoscopy. Cryostat sections of these biopsies were investigated using immunohistological techniques to determine the relative number of CD4/FAS+ and CD4/Bcl-2+ cells. Detection of IFN-gamma+ and IL-4+ was combined with TUNEL staining to determine the proportions of the Th1 and Th2 cells undergoing apoptosis. RESULTS: Experiments revealed raised proportions of activated CD4+ T cells as assessed by expression of HLA-DR and CD25+ expression in the asthmatic samples. Expression of Bcl-2 by the CD4+ cell population was significantly reduced in the asthmatic compared with the control group (P = 0.002). There was no significant difference in the expression of CD4+ Fas-ligand or the number of CD4+ undergoing apoptosis in the asthmatic and non-asthmatic groups. However, the IFN-gamma+ (P = 0.04) but not IL-4+ T cells in the asthmatic biopsies had significantly higher proportions of apoptotic cells compared with the control group. CONCLUSION: The evidence supports the hypothesis that Th1/Th2 imbalance in asthmatic inflammation may be a result of premature apoptosis within the Th1 subset.

Adolescent↗
PubMed2001

Immune responses of teleost fish.

In fish all the pre-requisites to mount a specific immune response are present, but the main differences from the mammalian system are that the secondary response is relatively minor and IgG is not present. In teleosts mainly IgM is present, and IgD has been recently described but its function is, as yet, unknown. However, different forms of fish IgM and its observed flexibility of structure may compensate for a lack of Ig class diversity. The innate immune response of teleosts is highly developed. Multiple forms of key constitutive and inducible components, such as lysozyme, C3, alpha2-macroglobulin and C-reactive protein, are present, and may enhance immune recognition. Low ambient temperature appears to have an impact on all aspects of the immune response, particularly the T-dependent specific immune response due to the non-adaptive lipid composition of T-cell membranes. Temperature effects on the nonspecific immune system are less well characterised, but there is evidence that low temperatures are also suppressive. Knowledge of immune system function becomes essential for disease prevention strategies such as the development of vaccines, selection for increased disease resistance and identification of genes suitable for trangenesis.

Animals↗
PubMed2001

Rapid dendritic cell recruitment to the bronchial mucosa of patients with atopic asthma in response to local allergen challenge.

BACKGROUND: Airway dendritic cells (DC) play an important role in chronic allergic airway inflammation in experimental animals, but a similar role for DC in human allergic asthma has been difficult to define. This pilot study was undertaken to elucidate the role of DC in allergic asthma by examining their potential to migrate to the lower airways in response to bronchial challenge with specific allergen. METHODS: Bronchial biopsy specimens were obtained from seven patients with allergic asthma before and 4-5 hours after allergen challenge. Multicolour immunofluorescence staining was performed on mucosal cryosections to identify changes in the number and phenotypes of DC. RESULTS: A dramatic increase in the number of CD1c+HLA-DR+ DC were observed in the lamina propria after challenge compared with baseline (22.4 v 7.8 cells/mm(2)). The rapid accumulation (within 4-5 hours) of these cells strongly suggests that they were directly recruited from peripheral blood. CONCLUSION: We have shown for the first time that a specific DC subset rapidly emigrates into the human bronchial mucosa during allergic inflammation. While this study is based on relatively few patients, the consistency of the overall results strongly suggests that the rapid population dynamics of human airway DC closely parallel those in animal models of acute inflammation. These findings support suggestions that DC have an important role in human airway allergy.

Adolescent↗
PubMed2000

Designing bronchial biopsy studies.

Bronchial biopsy provides valuable information about the inflammatory processes in lung tissue, but optimal results are only achieved if the design of intervention studies is sufficiently rigorous. The parallel-group design has merit, but the cross-over design is statistically superior, providing the wash-out period is effective. Heterogeneity of contributing pathologies in asthma patients results in large inter-patient variability which must be controlled for, for example by using strict inclusion criteria, which should ideally relate to the specific inflammatory marker being studied. The inclusion of a placebo group helps to quantify sample variability. The study must have sufficient statistical power to detect inter-group differences for each variable; appropriate adjustments should be made when multiple tests are used. Studies with larger patient numbers are best performed using a multi-centre design, with one centre analysing all tissue samples to reduce variability. Study duration depends on the type of investigation, but should ideally be short. Longer studies are necessary to evaluate chronic changes such as tissue remodelling. Changes in clinical status and cellular events may follow different time courses after intervention. Biopsy measurements are less reproducible than physiological tests, and diurnal variation in the number and function of inflammatory cells can further complicate measurement. The timing of clinical trial assessments needs to allow for these idiosyncrasies. Finally, a balance must be maintained between the risk, albeit small, and the benefit of performing bronchial biopsies.

Biopsy↗
PubMed2000

The anti-inflammatory profile of inhaled corticosteroids: biopsy studies in asthmatic patients.

The beneficial effects of inhaled corticosteroids in the treatment of asthma are well established. A potent topical anti-inflammatory action is assumed to underlie the therapeutic effect, given that these agents alter the number and function of a range of inflammatory cells and markers in airway biopsies. This activity profile is shown by all inhaled corticosteroids, in a variety of patient types and study designs. Thus, treatment with inhaled corticosteroids leads to consistent reductions in the number and activation of mast cells and eosinophils in biopsy specimens. Other relevant findings include reductions in T-lymphocytes, which contribute to chronic inflammation via the secretion of pro-inflammatory cytokines (some of which are responsible for eosinophil accumulation and activation). Inhaled corticosteroids may therefore act by down-regulating immunoreactivity, so reducing activation of T lymphocytes and (consequently) eosinophils. There is considerable interest in whether corticosteroids can inhibit or reverse some structural changes in the airways, including basement membrane thickening, collagen deposition and increased airway vascularity; it has been suggested that these changes may contribute towards airway hyperresponsiveness and irreversible airway obstruction. In summary, inhaled corticosteroids have a broad spectrum of anti-inflammatory activity in asthma patients, but the relationship between changes in clinical and immunopathological parameters, particularly in the long-term, requires further study.

Administration, Inhalation↗
PubMed2000

Fluticasone propionate-induced regulation of the balance within macrophage subpopulations.

In asthma, treatment with inhaled corticosteroids reduces chronic peribronchial inflammation and restores the balance within macrophage subpopulations. This study investigates whether corticosteroids can regulate monocyte differentiation in vitro and thereby influence the balance of functionally distinct macrophages. Graded doses of fluticasone propionate (FP) were added to cultures of normal peripheral blood monocytes in the presence or absence of IL-4. Cells were harvested after 7 days' culture. Double immunofluorescence studies were performed on cytospins of differentiated macrophages using the MoAbs RFD1 and RFD7 to distinguish inductive and suppressive macrophages by their respective phenotypes. Macrophage function was determined by quantifying allostimulation in a mixed leucocyte reaction and by measuring tumour necrosis factor-alpha (TNF-alpha) production. FP reduced the number of mature cells with a D1+ antigen-presenting phenotype and up-regulated the development of cells with the D1/D7+ and D7+ phenotypes. Functionally, this was associated with reduced stimulation of T cell proliferation in a mixed leucocyte reaction (MLR). Fluticasone also reversed the increase in both D1+ expression and TNF-alpha production induced by IL-4. The effect of FP persisted for 24 h after removal of FP from the culture medium. These results suggest that FP treatment of asthmatics may have a direct beneficial effect by normalizing the macrophage subset imbalance that contributes to the chronic peribronchial inflammation present in this condition.

Adrenal Cortex Hormones↗
PubMed1999

The reproducibility of repeat measures of airway inflammation in stable atopic asthma.

Measures of airway inflammation are increasingly being used as outcome measures in asthma intervention studies. Meaningful interpretation of observed changes in bronchial mucosal cell numbers should depend, in part, on the reproducibility of repeat measures over time. We wanted to investigate the reproducibility of immunopathologic and physiologic parameters after short and long measurement intervals. We therefore performed spirometry, bronchial provocation challenge, and fiberoptic bronchoscopy with endobronchial biopsy (always right upper lobe second-generation bronchus) at baseline, after 2 wk, and again after 8 wk on nine subjects with stable atopic asthma (receiving inhaled placebo and beta-agonist therapy only). Numbers of T cells, memory T cells (CD45Ro(+)), macrophages (CD68(+)), and eosinophils (EG1(+) and EG2(+)) on immunohistochemical stains of bronchial biopsies were quantified by computerized image analysis. Intraclass correlation coefficients (ICCs) of reproducibility were calculated for repeat measures of each parameter and a high ICC (greater than 0.6) was interpreted as "highly reproducible." Repeat measures of FEV(1), FEF(25-75%), and PC(20) were highly reproducible after short (2-wk) and long (8-wk) intervals. Only repeat measures of EG2(+) had an ICC greater than 0.6 after 8 wk. Repeat measures of CD45Ro(+), EG2(+), and T cell numbers (but not CD68(+) and EG1(+) cells) are highly reproducible and reliable parameters of asthmatic airway inflammation after a 2 wk interval.

Adolescent↗
PubMed1999

A comparison of the efficacy of long-acting beta 2-agonists: eformoterol via Turbohaler and salmeterol via pressurized metered dose inhaler or Accuhaler, in mild to moderate asthmatics. Force Research Group.

Four hundred and sixty nine patients were randomized to receive either 12 micrograms bd of eformoterol (Oxis, Astra Pharmaceuticals Ltd., Kings Langley, U.K.) delivered via Turbohaler or 50 micrograms bd salmeterol (Serevent, Glaxo-Wellcome Ltd., Uxbridge, U.K.) via either the Accuhaler (Glaxo-Wellcome Ltd.) or pressurized metered dose inhaler (pMDI, Glaxo-Wellcome Ltd.) for 8 weeks. This was followed by a 4-week cross-over period when patients who had received salmeterol in the previous 8 weeks were given eformoterol and patients who had received eformoterol were given either salmeterol via the Accuhaler or pMDI to assess patient device and treatment preference. For the primary efficacy variable, the increase in peak expiratory flow (PEF) rate from run-in to 8 weeks, similar significant improvements were seen in all three treatment groups. Eformoterol Turbohaler (FT) achieved a greater increase in morning PEF than salmeterol Accuhaler (SA) from randomisation to 4 weeks; the increase shown in the eformoterol Turbohaler group was 28.9 1 min-1 compared to 19.91 min-1 for the salmeterol Accuhaler group. The addition of eformoterol Turbohaler 12 micrograms bd, to patients' existing asthma therapy was found to have a significantly more beneficial effect on the severity of patients' daytime asthma symptoms than had salmeterol Accuhaler 50 micrograms bd (P = 0.014). Eformoterol Turbohaler reduced the severity of daytime asthma symptoms by 42% after only 4 weeks of treatment. The patients in the eformoterol Turbohaler treated group experienced a higher percentage of days when they were symptom-free and did not use their short-acting bronchodilator to relieve symptoms (32.8, 24.1 and 28.0% in the FT, SA and SM groups, respectively). At 8 weeks there were no significant differences in any of these variables between the three groups. Patients in all the treatment groups gained an additional 1-1.5 nights undisturbed by asthma per week. The changes in sleep disturbance were not significantly different between the three treatment groups. In addition to the therapeutic benefits provided by eformoterol Turbohaler the device (Turbohaler) was the significant preference of patients given both Turbohaler and pMDI (P = 0.0168) and was also considered to be significantly more convenient to carry around than the Accuhaler (P < 0.0001). No other differences were found between the three devices. The results of this study demonstrate that the addition of a long-acting beta 2-agonist is an effective tool for achieving the goals of asthma treatment. Eformoterol via the Turbohaler is at least as effective as salmeterol via either the Accuhaler or the pMDI in achieving these goals.

Adrenergic beta-Agonists↗
PubMed1999

A comparison of the efficacy of long-acting beta 2-agonists: eformoterol via Turbohaler and salmeterol via pressurized metered dose inhaler or Accuhaler, in mild to moderate asthmatics. Force Research Group.

Four hundred and sixty nine patients were randomized to receive either 12 micrograms bd of eformoterol (Oxis, Astra Pharmaceuticals Ltd., Kings Langley, U.K.) delivered via Turbohaler or 50 micrograms bd salmeterol (Serevent, Glaxo-Wellcome Ltd., Uxbridge, U.K.) via either the Accuhaler (Glaxo-Wellcome Ltd.) or pressurized metered dose inhaler (pMDI, Glaxo-Wellcome Ltd.) for 8 weeks. This was followed by a 4-week cross-over period when patients who had received salmeterol in the previous 8 weeks were given eformoterol and patients who had received eformoterol were given either salmeterol via the Accuhaler or pMDI to assess patient device and treatment preference. For the primary efficacy variable, the increase in peak expiratory flow (PEF) rate from run-in to 8 weeks, similar significant improvements were seen in all three treatment groups. Eformoterol Turbohaler (FT) achieved a greater increase in morning PEF than salmeterol Accuhaler (SA) from randomisation to 4 weeks; the increase shown in the eformoterol Turbohaler group was 28.9 l min-1 compared to 19.9 l min-1 for the salmeterol Accuhaler group. The addition of eformoterol Turbohaler 12 micrograms bd, to patients' existing asthma therapy was found to have a significantly more beneficial effect on the severity of patients' daytime asthma symptoms than had salmeterol Accuhaler 50 micrograms bd (P = 0.014). Eformoterol Turbohaler reduced the severity of daytime asthma symptoms by 42% after only 4 weeks of treatment. The patients in the eformoterol Turbohaler treated group experienced a higher percentage of days when they were symptom-free and did not use their short-acting bronchodilator to relieve symptoms (32.8, 24.1 and 28.0% in the FT, SA and SM groups, respectively). At 8 weeks there were no significant differences in any of these variables between the three groups. Patients in all the treatment groups gained an additional 1-1.5 nights undisturbed by asthma per week. The changes in sleep disturbance were not significantly different between the three treatment groups. In addition to the therapeutic benefits provided by eformoterol Turbohaler the device (Turbohaler) was the significant preference of patients given both Turbohaler and pMDI (P = 0.0168) and was also considered to be significantly more convenient to carry around than the Accuhaler (P < 0.0001). No other differences were found between the three devices. The results of this study demonstrate that the addition of a long-acting B2-agonist is an effective tool for achieving the goals of asthma treatment. Eformoterol via the Turbohaler is at least as effective as salmeterol via either the Accuhaler or the pMDI in achieving these goals.

Administration, Inhalation↗
PubMed1998

Dysregulation of monocyte differentiation in asthmatic subjects is reversed by IL-10.

BACKGROUND: IL-10 can modulate the differentiation of normal monocytes to macrophages, increasing the proportion of maturing cells with a phenotype consistent with T cell suppressive activity. Analysis of the immunopathology in endobronchial biopsies from asthmatic subjects has revealed significantly reduced proportions of suppressive macrophage populations associated with chronic T-cell mediated inflammation. OBJECTIVE: This study investigates whether the altered homeostasis within the lung macrophage populations in asthma is reflected in aberrant differentiation of peripheral blood monocytes and whether this differentiation may be influenced by IL-10. METHODS: Monocytes from 14 normal individuals and 14 atopic asthmatics were grown in culture for 7 days in the presence or absence of IL-10, added on day 5. Double immunofluoresence studies were performed on cytospins of the differentiated macrophages using the monoclonal antibodies RFD1 and RFD7 to distinguish inductive and suppressive macrophages by their respective phenotypes. HLADR expression was quantified using the monoclonal antibody RFDR1. Macrophage function was determined by quantifying allostimulation in a mixed leucocyte reaction and by measuring TNFalpha and TGFbeta production. RESULTS: With no cytokine addition the proportion of maturing macrophages with a suppressive phenotype (D1+D7+) at day 7 was lower in the asthmatic samples (18%) compared with normals (25%). IL-10 increased the proportion of suppressive cells in cultures of both asthmatic and normal monocytes with the increase in the asthmatic subjects (94% increase) being significantly greater than that in normal subjects (32% increase) (P<0.01). Asthmatic monocytes had a greater effect in stimulating MLR than normals (P < 0.05) but the addition of IL-10 reduced T cell proliferation in an MLR to a equivalent level in both groups. CONCLUSIONS: These results suggest that a fundamental problem may exist in the differentiation of monocytes in asthma which may be reversed by IL-10.

Adolescent↗
PubMed1998

Fluticasone propionate induced alterations to lung function and the immunopathology of asthma over time.

BACKGROUND: Inhaled corticosteroids are the most widely used treatment for asthma, a disease characterised by both functional and immunopathological abnormalities. This study investigated the relative effects of inhaled corticosteroids on these two features of asthma over time. METHODS: A randomised, double blind, placebo controlled, parallel group study with inhaled fluticasone propionate, (FP 2 mg daily) was conducted in 27 patients with asthma. Following baseline analysis, the study tested the effects of short term (two weeks) and longer term (eight weeks) treatment. At each time point (0, 2, and 8 weeks) lung function tests were performed and endobronchial biopsy specimens obtained to determine the distribution and number of lymphocyte, macrophage and eosinophil subsets using immunohistological analysis. Twenty three patients completed the study, 11 on FP and 12 placebo. RESULTS: FEV1, delta FEV1, FEF25-75, and FEV1/FVC all improved after two weeks of FP treatment. This improvement was maintained but not increased after eight weeks. PC20FEV1 showed a trend to increase but was not significantly improved at eight weeks. No significant changes were seen in the placebo group. The numbers of T cells, macrophages, and eosinophils in the bronchial wall were reduced by two weeks of treatment with FP but were unaltered by placebo. The improvement offered by FP continued over the eight week period. Reductions in CD4:CD8 ratio and numbers of activated (EG2+) eosinophils were only significant after eight weeks of treatment. CONCLUSIONS: These results reveal that FP influences both functional and immunopathological parameters of asthma. Temporal relationships suggest that these are parallel but not necessarily interrelated effects. While short term treatment is effective in "normalising" the functional abnormalities in asthma, the impact of FP on bronchial inflammation appears to be progressive, taking up to eight weeks and more.

Administration, Topical↗