CRTH2 expression on T cells in asthma

Mast 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 < 0·001). There was a small population of CRTH2+ T cells in the bronchoalveolar lavage (BAL) of asthmatics (2·3% ± 0·6) and normal subjects (0·3% ± 0·1), and there was a significant difference between the two groups (P < 0·05). There were similar amounts of PGD2 in the BAL of asthma and normal subjects. Within paired blood–BAL samples from the same subject there was no increase in CRTH2+ T cells in the BAL compared to blood in asthmatics. Enrichment of CRTH2 on IL-4+ and IL-13+ T cells compared to IFN-γ+ T cells was also seen in BAL from asthmatics (P < 0·001). CRTH2 is expressed preferentially by IL-4+/IL-13+ T cells compared to IFN-γ+ T cells. However, given their small numbers they are unlikely to have a significant involvement in the pathogenesis of asthma. CRTH2 antagonism may not diminish T cell accumulation in the asthmatic lung

T lymphocyte Recruitment to the Lung in Asthma

T cells play an important part in the pathogenesis of asthma. In this study greater numbers of T cells were seen in the bronchial epithelium of severe asthmatics compared to normal subjects. There were greater percentages of both IL-4+ and IFN-γ+ T cells in the bronchoalveolar lavage of asthmatics compared to normal subjects. Chemokines and their receptors are thought to act as signals that guide particular subsets of T cells to the lung in asthma. Using flow cytometry I had explored whether the chemokine receptors CCR8 and CRTh2 played any role in recruiting T cells and in particular IL-4+ T cells to the lung in asthma. Both receptors selectively identified IL-4+ and IL-13+ T cells in the blood and bronchoalveolar lavage from asthmatics and normal subjects. Cells expressing CCR8 but not CRTh2 were found at a higher percentage in the blood of severe asthmatics compared to normal controls. The percentage of CCR8+ T in the bronchoalveolar lavage of asthmatics was higher compared to normal subjects and furthermore, there was a greater percentage of CCR8+ T cells in the bronchoalveolar lavage compared to blood within the same asthmatic subject. This difference in the percentage of CCR8+ T cells between blood and BAL was not seen in normal subjects. This suggests that there may be a role for CCR8 in the recruitment of T cells to the lung in asthma. In support of this, higher concentrations of the ligand CCL1, were seen in the bronchoalveolar lavage of asthmatics compared to that from normal subjects. Little experimental evidence was found that supported the contention that CRTh2 played a significant role in T cell recruitment to the lung. As a marker of IL-4+ T cells in asthmatics, CCR8 compared favourably with CRTh2 as they identified a greater percentage of IL-4+ T cells in bronchoalveolar lavage than CRTh2. CCR8 also compared favourably with CCR4 as a marker for IL-4+ T cells due to higher specificity. The iNKT subset of T cells has been claimed to be an important group of T cells in asthma and was reported to be present at high percentages in the lung of moderate to severe asthmatics. In this study we had shown that in asthmatics these cells are present in very low percentages, similar to that in normal subjects and that they probably do not play a significant role in severe asthma

T lymphocyte recruitment to the lung in asthma

T cells play an important part in the pathogenesis of asthma. In this study greater numbers of T cells were seen in the bronchial epithelium of severe asthmatics compared to normal subjects. There were greater percentages of both IL-4+ and IFN-γ+ T cells in the bronchoalveolar lavage of asthmatics compared to normal subjects. Chemokines and their receptors are thought to act as signals that guide particular subsets of T cells to the lung in asthma. Using flow cytometry I had explored whether the chemokine receptors CCR8 and CRTh2 played any role in recruiting T cells and in particular IL-4+ T cells to the lung in asthma. Both receptors selectively identified IL-4+ and IL-13+ T cells in the blood and bronchoalveolar lavage from asthmatics and normal subjects. Cells expressing CCR8 but not CRTh2 were found at a higher percentage in the blood of severe asthmatics compared to normal controls. The percentage of CCR8+ T in the bronchoalveolar lavage of asthmatics was higher compared to normal subjects and furthermore, there was a greater percentage of CCR8+ T cells in the bronchoalveolar lavage compared to blood within the same asthmatic subject. This difference in the percentage of CCR8+ T cells between blood and BAL was not seen in normal subjects. This suggests that there may be a role for CCR8 in the recruitment of T cells to the lung in asthma. In support of this, higher concentrations of the ligand CCL1, were seen in the bronchoalveolar lavage of asthmatics compared to that from normal subjects. Little experimental evidence was found that supported the contention that CRTh2 played a significant role in T cell recruitment to the lung. As a marker of IL-4+ T cells in asthmatics, CCR8 compared favourably with CRTh2 as they identified a greater percentage of IL-4+ T cells in bronchoalveolar lavage than CRTh2. CCR8 also compared favourably with CCR4 as a marker for IL-4+ T cells due to higher specificity. The iNKT subset of T cells has been claimed to be an important group of T cells in asthma and was reported to be present at high percentages in the lung of moderate to severe asthmatics. In this study we had shown that in asthmatics these cells are present in very low percentages, similar to that in normal subjects and that they probably do not play a significant role in severe asthma.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Improvement in health status following bronchopulmonary hygiene physical therapy in patients with bronchiectasis.

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 &gt;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&lt;0.0001) and cough-related health status after BHPT (mean LCQ total score before 14.2 vs after 17.3; mean difference 3.1; 95% confidence interval of difference 2.4-3.9; p&lt;0.001). A significant improvement was seen in all LCQ health-related domains (physical, psychological and social; all p&lt;0.001). Our findings suggest that bronchopulmonary hygiene physical therapy can lead to a significant improvement in cough-related quality of life

Improvement in health status following cough-suppression physiotherapy for patients with chronic cough.

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 &lt; 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 &lt; 0.001) and social (p &lt; 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

Inhaled non-steroid anti-inflammatories for children and adults with bronchiectasis (Review)

Free to read Plain language summary: Inhaled non-steroid anti-inflammatories (NSAIDs) for children and adults with bronchiectasis People with bronchiectasis experience chronic inflammation of the lungs. Anti-inflammatory effects of inhaled non-steroid anti-inflammatory drugs (NSAIDs) may be beneficial for patients with bronchiectasis. However, short-term and long-term benefits in adults and children must be investigated, in addition to potential side effects of NSAIDs used over the long term. Results We included one small study on 25 people with chronic lung disease. Of those 25, only eight people had bronchiectasis. Other individuals had chronic bronchitis of diffuse panbronchiolitis and were at risk for bronchiectasis. However, we must remember when interpreting the results that not all study participants had bronchiectasis. Overall, the small study reported improvement in sputum production and dyspnoea (shortness of breath) in adults with chronic lung disease (chronic bronchitis, bronchiectasis or diffuse panbronchiolitis) who received inhaled indomethacin compared with placebo. Researchers observed no significant improvement in lung function (forced expiratory volume in one second (FEV1) and vital capacity (VC)) and reported no adverse events. Conclusions The small scale of this study and collective analysis of data from the three disease states made it difficult for review authors to draw solid conclusions on the benefit of using NSAIDs to treat adults with bronchiectasis. Review authors identified no studies examining the use of NSAIDs in children with bronchiectasis