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RATIONALE: The importance of Aspergillus fumigatus sensitization and colonization of the airways in patients with asthma is unclear. OBJECTIVES: To define the relationship between the clinical and laboratory features of A. fumigatus-associated asthma. METHODS: We studied 79 patients with asthma (89% classed as GINA 4 or 5) classified into 3 groups according to A. fumigatus sensitization: (1) IgE-sensitized (immediate cutaneous reactivity > 3 mm and/or IgE > 0.35 kU/L); (2) IgG-only-sensitized (IgG > 40 mg/L); and (3) nonsensitized. These were compared with 14 healthy control subjects. Sputum culture was focused toward detection of A. fumigatus and compared with clinical assessment data. MEASUREMENTS AND MAIN RESULTS: A. fumigatus was cultured from 63% of IgE-sensitized patients with asthma (n = 40), 39% of IgG-only-sensitized patients with asthma (n = 13), 31% of nonsensitized patients with asthma (n = 26) and 7% of healthy control subjects (n = 14). Patients sensitized to A. fumigatus compared with nonsensitized patients with asthma had lower lung function (postbronchodilator FEV₁ % predicted, mean [SEM]: 68 [±5]% versus 88 [±5]%; P < 0.05), more bronchiectasis (68% versus 35%; P < 0.05), and more sputum neutrophils (median [interquartile range]: 80.9 [50.1-94.1]% versus 49.5 [21.2-71.4]%; P < 0.01). In a multilinear regression model, A. fumigatus-IgE sensitization and sputum neutrophil differential cell count were important predictors of lung function (P = 0.016), supported by culture of A. fumigatus (P = 0.046) and eosinophil differential cell count (P = 0.024). CONCLUSIONS: A. fumigatus detection in sputum is associated with A. fumigatus-IgE sensitization, neutrophilic airway inflammation, and reduced lung function. This supports the concept that development of fixed airflow obstruction in asthma is consequent upon the damaging effects of airway colonization with A. fumigatus.

Cough-suppression physiotherapy is a novel self-help therapy for chronic cough. We evaluated the effectiveness of cough physiotherapy in a pilot prospective observational study. We assessed cough-specific health-related quality of life (HRQOL) with the Leicester Cough Questionnaire (LCQ) and subjectively reported cough frequency and sleep disturbance in 23 patients with chronic cough refractory to medical therapy, before and after outpatient-based cough-suppression physiotherapy. Cough-suppression physiotherapy consisted of education, counselling, cough control, breathing retraining, and vocal hygiene. There was a significant improvement in cough-specific HRQOL after cough physiotherapy; mean (standard error of mean [SEM]) LCQ total score before 12.4 (0.9) versus after 15.1 (0.9); 95% confidence interval of difference −4.1 to −1.3; p < 0.001. The improvement in cough-specific HRQOL was greater than the LCQ minimal clinically important difference of 1.3. A significant improvement was seen in all LCQ domains: physical ( p = 0.001), psychological ( p < 0.001) and social ( p < 0.04). There was a significant reduction in cough frequency scores ( p = 0.002) and sleep disturbance scores ( p = 0.02). Our findings suggest cough-suppression physiotherapy may lead to a clinically significant improvement in cough-specific HRQOL in patients with chronic cough.

BACKGROUND: Chemokines and their receptors could play key roles in the recruitment of T cells to the asthmatic lung. CCR8 is preferentially expressed on T-helper type 2 cells, and is thought to play a role in the pathogenesis of human asthma. OBJECTIVE: Determine the expression of CCR8 on T cells in blood, bronchoalveolar lavage (BAL) and bronchial mucosa from asthmatics and normal subjects. METHODS: CCR8 expression in blood and BAL from asthma and normal subjects was studied using flow cytometry. CCR8 expression on IFN-gamma+ and IL-4+/IL-13+ blood and BAL T cells was studied following stimulation with Phorbol-Myristate-Acetate and Calcium Ionophore. Paraffin-embedded bronchial biopsies were used to study CCR8 in bronchial epithelium. RESULTS: The percentage of CD3+ cells expressing CCR8 in the blood was higher in asthmatics (4.7+/-0.4%) compared with normal subjects (3.0+/-0.4%; P

This paper was published as Clinical and Experimental Allergy, 2009, 39 (12), p. 1937: British Society for Allergy and Clinical Immunology Annual Conference 2009 Abstracts, S2. It is available from http://www3.interscience.wiley.com/journal/122683542/issue. Doi: 10.1111/j.1365-2222.2009.03389.x

Chronic productive cough is a common symptom in patients with bronchiectasis that is associated with a reduction in health-related quality of life (QOL). Bronchopulmonary hygiene physical therapy (BHPT) is widely prescribed for patients with bronchiectasis, although the evidence for its efficacy is limited. We set out to prospectively evaluate the impact of BHPT on health-related QOL in patients with non-cystic fibrosis bronchiectasis. We assessed cough symptoms (0-100mm visual analogue scale; VAS) and cough-related QOL in 53 patients with stable non-cystic fibrosis bronchiectasis at baseline and >4 weeks after outpatient-based BHPT. Cough specific health status was assessed with the Leicester Cough Questionnaire (LCQ; total score range 3-21, higher scores representing better QOL). All patients with bronchiectasis complained of cough as the major symptom and had mean (SEM) FEV(1) of 2.1 (0.1)L. Cough-related health status was reduced at baseline; mean (SEM) LCQ score 14.3 (0.6). There were significant improvements in cough symptoms (mean cough VAS before 43.3 (3.6) vs after 27.5 (3.1); mean difference 15.8; 95% CI of difference 9.6-22; p

SummaryBackground Fungal 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. Objective To 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. Methods We 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. Results Forty-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

SummaryMast cell-derived prostaglandin D2 (PGD2) is the major prostanoid found within the airway of asthmatics immediately following allergen challenge. PGD2 has been shown to have chemokinetic effects on eosinophils and T helper type 2 (Th2) cells in vitro. This occurs through the interaction of PGD2 with the G-protein-coupled chemokine receptor homologous molecule expressed on Th2 lymphocytes (CRTH2). The expression of CRTH2 has been shown to be highly selective for Th2 cells. Using flow cytometry we have studied the expression of CRTH2 on T cells in blood and bronchoalveolar lavage fluid in asthmatics and normal subjects. CRTH2 expression was confined to a small percentage of blood T cells in asthmatics (1·8% ± 0·2) and normal (1·6% ± 0·2) subjects. CRTH2 was enriched significantly on interleukin (IL)-4+/IL-13+ T cells compared to interferon (IFN)-γ+ T cells (P

Introduction and objectives IgE sensitisation to fungal allergens is common in severe asthma, but the clinical relevance of this, and the relationship to airway colonisation with fungi, is not known. Many of the fungi that can grow at body temperature are filamentous moulds from the genera Aspergillus and Pencillium . We report here the relationship between lung function and fungal sputum culture in patients with severe asthma. Methods We recruited 126 patients attending a tertiary referral centre with a diagnosis of asthma and 18 healthy volunteers. 93% of patients were on GINA treatment step 4 or higher. At a single stable visit subjects underwent: spirometry with reversibility to 200 μg salbutamol; sputum fungal culture and a sputum cell differential count; skin prick testing to both common aeroallergens and an extended fungal panel (+ve ≥3 mm); specific IgE to Aspergillus fumigatus by CAP (positive >0.35 kU/l). Fungi were identified by morphology and species identity confirmed by sequencing regions of the nuclear ribosomal operon. Results Patients had a mean age of 56 years (21–84 years); 48% were males with median ICS dose of 800 μg Fluticasone equivalent. 60% were atopic to common aeroallergens, 45% were IgE sensitised to one fungal allergen and 27% to ≥2 fungal allergens. 64% of patients cultured a mould in their sputum, 7% more than one species. This compared with three healthy subjects (17%) culturing any mould (p Aspergillus species were most frequently cultured (n=58) followed by Penicillium species (n=15) and Thermoascus species (n=2), others (n=8). Four fungal genera were cultured from healthy volunteers sputum,- Aspergillus , Penicillium, Coprinus and one other. Post bronchodilator FEV 1 % predicted was 71% in those with a positive fungal culture vs 84% in those who were culture negative, (p Conclusions In addition to IgE fungal sensitisation, sputum culture focused towards detection of moulds is frequently positive and associated with impaired post-bronchodilator FEV1. Colonisation of the airways with mould in asthma could be responsible for the development of fixed airflow obstruction.