Background-Airway hyperresponsiveness, induced sputum eosinophils, and exhaled nitric oxide (NO) levels have all been proposed as non-invasive markers for monitoring airway inflammation in patients with asthma. The aim of this study was to compare the changes in each of these markers following treatment with inhaled glucocorticosteroids in a single study. Methods-In a randomised, double blind, placebo controlled, parallel study 25 patients with mild asthma (19-34 years, forced expiratory volume in one second (FEV 1 ) >75% predicted, concentration of histamine provoking a fall in FEV 1 of 20% or more (PC 20 ) <4 mg/ml) inhaled fluticasone propionate (500 µg twice daily) for four weeks. PC 20 to histamine, sputum eosinophil numbers, and exhaled NO levels were determined at weeks 0, 2, and 4, and two weeks after completing treatment. Sputum was induced by inhalation of hypertonic (4.5%) saline and eosinophil counts were expressed as percentage nonsquamous cells. Exhaled NO levels (ppb) were measured by chemiluminescence. Results-In the steroid treated group there was a significant increase in PC 20 , decrease in sputum eosinophils, and decrease in exhaled NO levels compared with baseline at weeks 2 and 4 of treatment. Subsequently, each of these variables showed significant worsening during the two week washout period compared with week 4. These changes were significantly diVerent from those in the placebo group, except for the changes in sputum eosinophils and exhaled NO levels during the washout period. There were no significant correlations between the changes in the three markers in either group at any time. Conclusions-Treatment of asthmatic subjects with inhaled steroids for four weeks leads to improvements in airway hyperresponsiveness to histamine, eosinophil counts in induced sputum, and exhaled nitric oxide levels. The results suggest that these markers may provide diVerent information when monitoring anti-inflammatory treatment in asthma.

Asthma is characterized by the accumulation of activated T cells and eosinophils within the airway. Eosinophils derive from CD34(+) bone marrow progenitor cells under the influence of hematopoietic growth factors, subsequently migrating to the airways under the cooperative influence of interleukin (IL)-5 and chemokines, including eotaxin. We compared the relative effects of systemic versus local IL-5 on progenitor-cell mobilization and mature eosinophil phenotype by using flow cytometry, following the administration of intravenous (2 microg) or inhaled (15 microg) IL-5 to nine patients with mild asthma. Intravenous IL-5 induced a rapid reduction in circulating eosinophil counts followed by prolonged blood eosinophilia. Both intravenous (p < 0.002) and inhaled (p < 0.05) IL-5 significantly increased CD34(+)/CD45(+) lymphoblastoid eosinophil progenitors. Intravenous IL-5 increased mature eosinophil CCR3 expression from a baseline mean fluorescence intensity (MFI) of 658 +/- 51.7 to 995 +/- 93.2 at 24 h (p < 0.05), but had no effect on interleukin-5 receptor subunit alpha or CD11b expression. Lymphocyte CCR3 MFI was increased by intravenous IL-5 from 38.5 +/- 13.6 at baseline to 73.6 +/- 14.3 at 24 h (p < 0.05). Systemic IL-5 increased circulating eosinophil progenitors, suggesting a key role for systemic IL-5 in eosinophil mobilization. Further, IL-5 causes terminal maturation of the eosinophil by increasing CCR3 expression, potentially affecting CCR3-dependent chemotaxis by eosinophils and lymphocytes.

The outcome of asthma, as determined by the annual decline in FEV1, can be predicted by the bronchial CD8+ cell infiltrate. This suggests that the inflammatory phenotype in asthma has prognostic relevance, which may require phenotype-specific therapeutic strategies.

The response to inhaled allergen in asthma is diminished by anti-IgE, which in bronchial mucosa is paralleled by a reduction in eosinophils and a decline in IgE-bearing cells postallergen without changing PC(20) methacholine. This suggests that the benefits of anti-IgE in asthma may be explained by a decrease in eosinophilic inflammation and IgE-bearing cells.

With the rise of clinical management, new skills of medical doctors stand out, including leadership skills. Medical doctors organize medical work and improve patient care. The training of frontline leadership skills, however, is weakly developed in residency programmes. Medical professional cultures tend to resist organizational techniques and values. This paper analyses cultural interventions in health-care organizations, aimed at overcoming 'clashes' between professional and organizational logics in frontline domains. These interventions do not work against, but 'use' professional traditions, styles and customs as cultural resources. We use one particular project to illustrate this, a project in which internal medicine residents are invited to join quality improvement sessions, during which they identify critical (organizational) experiences with care provision and realize change. We show how residents feel enabled to establish results and cooperate with other professionals. We also show how this project links organizational responsibilities and medical professionalism -how complementarity (instead of conflict) is established. This is done in practical ways, which commit instead of alienate medical professionals.