Jz Sun

Overexpression of matrix metalloproteinase‐8 and ‐9 in bronchiectatic airways in vivo

The progressive bronchial dilatation in bronchiectasis is likely to be the result of continued airway matrix destruction, although little is known about the role of neutrophil matrix metalloproteinases (MMPs) in this process. Immunohistochemistry has been used to investigate the expression and cellular localisation of MMP‐8 and MMP‐9 in bronchiectatic airways in vivo. Endobronchial biopsies were taken from 25 bronchiectatic patients, and from the right lower lobe in 14 control subjects. MMP‐8, MMP‐9, neutrophils and macrophages were stained with monoclonal antibodies and quantified as positive cell·mm−2 of the lamina propria by using an image analysis system. There were significantly higher densities of MMP‐8 and MMP‐9 positive cells in the lamina propria of bronchiectatic than control airways. In bronchiectatic airways, the densities of MMP‐8 and MMP‐9 positive cells correlated with each other and with neutrophil density, but not with macrophage density. In control airways, a significant correlation was found between MMP‐8 with neutrophil and MMP‐9 with macrophage densities. An overexpression of neutrophil matrix metalloproteinases in bronchiectatic airways could help explain the continuation of airway destruction in bronchiectasis. In view of the clinical availability of matrix metalloproteinase antagonists, the results presented here could have a significant impact on the development of novel therapies of this untreatable disease.

Effects of erythromycin on Pseudomonas aeruginosa adherence to collagen and morphology in vitro

The airways of patients with bronchiectasis and cystic fibrosis are often chronically colonised by Pseudomonas aeruginosa (PA), which is virtually impossible to eradicate. Low-dose erythromycin (EM), for unknown mechanisms, is efficacious in bronchiectasis and diffuse panbronchiolitis. In this study, an in vitro model to investigate PA adherence to human type IV basement collagen was developed by using scanning electron microscopy (SEM). There were significantly less PA bacilli per 20 random SEM fields (4,000×) when PA was cultured in 0.05, 0.5 and 5 µg·mL−1 of EM compared with control (absence of EM). Adherence density (20 SEM fields·log−1 inocular size) for PA obtained from no EM (56.8±43.16) was significantly higher than that obtained from 0.05, 0.5, and 5 µg·mL−1 EM (21.5±17.56, 23.3±16.65, and 21.4±12.65 respectively). By using SEM it was found that PA, when incubated in EM (0.05, 0.5, 5 µg·mL−1) had a significant reduction in its diagonal length, radius, height, volume and surface area. It is possible, therefore, that these misshaped Pseudomonas aeruginosa bacilli are more susceptible to host defence mechanisms, while at the same time less adherent to the basement membrane of the airway in vivo. Therefore, this could help explain the clinical efficacy of low-dose erythromycin therapy on patients with Pseudomonas aeruginosa infection.

Respiratory ciliary function in bone marrow recipients.

Bone marrow transplantation (BMT) recipients, particularly those with chronic graft-versus-host disease (GVHD), suffer from respiratory tract problems, including bronchiolitis obliterans (BO) and recurrent lower respiratory tract infections. Minute cilia beat continuously on the surface of respiratory mucosa, and this beating maintains the sterility of the lower respiratory tract. Dysfunction of respiratory cilia could lead to development of recurrent respiratory tract infections, which are also features of BMT recipients, although ciliary function has not been systematically studied among these subjects. We have, therefore, investigated the ciliary beat frequency (CBF) of 36 Chinese patients who had undergone allogeneic BMT. The CBF was significantly lower in the BMT group compared to controls (P < 0.001). The reduction in CBF was more severe in patients with cGVHD and BO compared with their counterparts (P = 0.048 and P = 0.077, respectively). There was a correlation between CBF with forced expiratory flow rate FEF (P = 0.024) and forced expiratory volume FEV (P = 0.044). We conclude that abnormal ciliary clearance is a common feature after allogeneic BMT, particularly among patients with BO and cGVHD. Further studies are indicated to evaluate this important phenomenon, which could be an important cause of the susceptibility for BMT recipients to respiratory infections. Bone Marrow Transplantation (2001) 27, 1147–1151.

Regression of bilateral bronchiectasis with inhaled steroid therapy.

Abstract: Bronchiectasis is defined as pathological and permanent dilatation of the bronchial tree. Affected patients suffer from chronic sputum production and usually slowly progressive airway destruction as a result of continued airway infection and inflammation. Regression of bilateral bronchiectasis has never been reported in the English literature. We report the case of a 60‐year‐old woman with longstanding progressive idiopathic bilateral bronchiectasis whose respiratory symptoms, including sputum, rapidly disappeared after commencement of inhaled budesonide. Repeat computed tomography assessment 40 months after commencement of inhaled steroid therapy, showed partial regression of bronchial dilation and resolution of small airways sepsis. In the absence of other possible explanations for the partial resolution of the bronchiectasis, the present case suggests a possible benefit of inhaled steroid therapy in bronchiectasis.

Clinical value of ciliary assessment in bronchiectasis.

Although ciliary dysfunction and numerous ultrastructural defects have been described, and these could be etiologically important in the development of bronchiectasis, their correlation with relevant clinical parameters have not been systematically evaluated. We have prospectively evaluated the prevalence and clinical significance of ciliary beat frequency and ultrastructural defects of nasal respiratory mucosa obtained from 152 stable patients with idiopathic bronchiectasis (100F, 57.7±15.2 yrs) and 127 control subjects (58F, 56.0±24.2 yrs). Bronchiectasis patients had significantly slower ciliary beat frequency (p < 0.05), and a greater percent of patients had central and peripheral microtubular defects (OR 14.4, 95% CI 5.6-36.8), namely, extra peripheral microtubules, “9+1”, “8+2”, and compound cilia (p < 0.05), but not microtubular disarrangement, extra matrix or ciliary tail abnormalities (p > 0.05), than controls. Bronchiectasis patients also had a greater proportion of cilia with any ultrastructural microtubular defects, compound cilia, and ciliary tails than controls (p < 0.05). Ciliary beat frequency did not correlate with clinically relevant parameters (p > 0.05). However, the percent of cilia with central, but not peripheral, microtubular defects correlated with 24 h sputum volume (r = 0.40, p = 0.001, and r = −0.04, p = 0.70, respectively) and FEV1 (r = −0.24, p = 0.01, and r = 0.00, p =0.99 respectively). Our results strongly suggest a pathogenic role for central microtubular defects in the development of idiopathic bronchiectasis.

A prospective study of respiratory ciliary structure and function after stem cell transplantation

We prospectively investigated the morphological and ciliary function abnormalities in 19 consecutive Chinese patients undergoing hemopoietic stem cell transplantation (HSCT) and studied their relationship with pulmonary complications. The percentage of structural ciliary abnormalities preceding HSCT was comparable to normal controls, but increased up to 1-year post-HSCT. However, the abnormalities did not correlate with ciliary or pulmonary function. Ciliary beat frequency (CBF) for patients undergoing autologous and allogeneic SCT was lower than that of matched controls, with a further decline at one year. There was, however, no significant change in pulmonary function for the whole cohort. There was considerable variation in CBF and ciliary abnormalities in all cases during 3-month interval assessments. Regular ciliary assessment did not predict the only two patients who eventually suffered from bronchiolitis obliterans (BO). We conclude that structural and functional ciliary abnormalities are common in recipients of HSCT, and predict post-HSCT deterioration. However, there is no evidence to show that CBF monitoring may be of prospective benefit.

Endobronchial Foreign Body Presenting as Exacerbation of Asthma

Airway foreign bodies are a leading cause of death among children and require urgent recognition by medical personnel. While most cases are diagnosed readily from a clinical history of acute respiratory distress, some cases remain more indolent and present later. We report the case of a 7-year-old boy who aspirated a “LEGO” toy and presented with a week history of increasing respiratory distress compatible with known asthma. Despite a normal chest X-ray, a low-dose computed tomography showed the presence of a foreign body in the left main bronchus, which was subsequently removed by fiberoptic bronchoscopy. Our case serves to reemphasize the importance of considering airway foreign bodies as a cause of respiratory distress, especially in young children.

The effects of gelomyrtol forte on human ciliary beat frequency in vitro

for the 9th Congress of the Asian Pacific Society of Respirology 10–13 December 2004, Hong Kong Editors: Dr K.S. Chan Dr P.C. Wong A DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF HOUSE DUST MITE IMMUNOTHERAPY IN ASTHMATIC PATIENTS IN CHINA HONGYU WANG1, XIAOPING LIN2, CHUANGLI HAO3, CHUNQING ZHANG1, BAOQING SUN1, JINGPING ZHENG1, PING CHEN2, JINYUN SHENG3, ADRIAN WU4, NANSHAN ZHONG1 1Guangzhou Institute of Respiratory Diseases, 2Shenyang General Military Hospital, 3Suzhou Children’s Hospital, 4Department of Medicine, The University of Hong Kong Background The purpose of this study was to determine if house dust mite immunotherapy is effective in improving symptom control and reducing rescue medication use in Chinese patients with mild to moderate allergic asthma. Methods This is a double-blind, placebo-controlled study involving 132 asthmatic subjects aged 6 to 45 years recruited from 3 different regions of Mainland China. Subjects were given a 52-week course of Alutard Der P (ALK-Abello, Horsholm, Denmark) treatment or placebo while the dose of inhaled corticosteroids (ICS) was maintained. Results 129 subjects (64 active) completed the study. The symptom scores began to diverge at week 25 with the immunotherapy group showing a significantly lower score until week 48 (P = 0.018). Immunotherapy resulted in a significant decline in symptom (P = 0.003) and medication (P = 0.044) scores during the second half of the treatment period only in subjects who were taking ICS. Subjects on ICS also showed significant improvement in PEF after immunotherapy, but no difference in histamine PC20 was found. Serum ECP and blood eosinophils decreased after immunotherapy in subjects not using ICS. Skin test response decreased in immunotherapy subjects only, and Der P-specific IgE decreased in placebo but not immunotherapy subjects. Immunotherapy resulted in a significantly greater improvement in self-evaluation scores (P < 0.01). Conclusions One year of immunotherapy with Alutard Der P significantly reduced symptoms and medication use in asthmatic subjects, particularly in those who were already using ICS. This was associated with a greater subjective improvement in asthma control. 002 Respirology (2004) 9, (Suppl.) A79–A164 ASSOCIATION OF TOTAL PLASMA IGE LEVELS AND ASTHMA IN ASIAN POPULATIONS WD ZHANG, XZ ZHANG, DW QIU, WC TAN Department of Medicine, National University of Singapore Background Previous studies demonstrated that high levels of serum IgE was associated with asthma and other allergic diseases. Objectives To determine and compare the total plasma IgE levels in both asthmatics and healthy controls in Chinese, Malay and Indian in Singapore. Methods Both 311 asthmatics (Chinese 150; Malay 74; Indian 87) and 355 healthy subjects (Chinese 156; Malay 98; Indian 101) were being participated in a genetic study of asthma. Total plasma IgE levels were determined by Enzyme-linked immunosorbent assay (ELISA). A binary logistic model was used to detect the association between total plasma IgE levels and asthma. Results Plasma total IgE was significantly higher in patients group than that of control group in each ethnicity (Chinese: P = 0.049; Malay: P = 0.002; Indian: P = 0.000). Plasma total IgE (Geometric mean) in Chinese (382 IU/ml) was significantly lower than that in Malay (584 IU/ml) and Indian (990 IU/ml) in the patient group (P = 0.000). However, there was no difference for plasma total IgE among Chinese (256 IU/ml), Malay (226 IU/ml) and Indian (323 IU/ml) (P = 0.385) in the control group. Conclusion High level of plasma total IgE may be a risk factor for asthma in Chinese, Malay and Indian. Total plasma IgE levels showed homogeneous among the three ethnicities. TIME TRENDS IN THE PREVALENCE OF ALLERGIC DISEASES IN GUANGZHOU CHILDHOOD HONGYU WANG, JINGPING ZHENG, NANSHAN ZHONG Guangzhou Institute of Respiratory Disease 510120 Guangzhou, China Objective To examine time trends in the prevalence of asthma, allergic rhinoconjunctivitis and atopic eczema in childhood. Methods 3575 Children aged 13–14 years were randomly selected from ten middle schools in the four central districts of Guangzhou city in 2001. The selection followed the methods used for ISAAC Phase I in 1994–1995. All subjects completed the written questionnaire on asthma, rhinitis and eczema, then finished the video questionnaire about asthma. Results The response rate was 96%, 50.9% of them were female. With the written questionnaire /video questionnaire, the prevalence of wheezing ever, wheezing in the past year, wheezing related to exercise were 8.6%/5.9%, 4.8%/3.8%, 23.4%/11.3% respectively, revealed significantly higher than that were 6.2%/3.2%, 3.4%/2.0%, 17.4%/6.9% in the Phase I (P < 0.001). The prevalence of asthma ever were 4.6%, similar as 3.9% in the Phase I (P > 0.05). The positive response rate to all the questions related to rhinitis and eczema (P < 0.05) except eczema ever (P > 0.05) were significantly higher than that in Phase I. Conclusions The prevalence of asthma, allergic rhinoconjunctivitis and atopic eczema in childhood were increasing during 7 years periods in Guangzhou. STUDY OF ROLE OF INSULIN AND INSULIN RECEPTOR IN ALLERGIC AIRWAY INFLAMMATION OF RATS YL MA, QY HE Department of Pulmonary Medicine People’s Hospital, Peking University, Beijing, P.R.C. 100044 Background Bronchial asthma and type 1 diabetes mellitus (IDDM) are rarely associated in the same subject although the mechanism is still unclear. Methods Streptozotocin and ovalbumin (OVA) were respectively used to induce diabetes mellitus and allergic airway inflammation. 64 male SD rats were divided into 8 groups: group A (asthma); group D (diabetes); group I (insulin treated); group AD (asthma + diabetes); group AI (asthma + insulin treated); group DI (diabetes + insulin treated); group ADI (asthma + diabetes + insulin treated); group C (control). Blood glucose measurements, serum insulin measurements, total and differential leukocyte counts of blood and BALF, HE stained paraffin section of lung tissue were carried out. Immunohistochemistry method was used to describe the distribution of insulin receptor, and the expression of insulin receptor mRNA were measured by RT-PCR. Results After antigen challenge, rats of group A, AI, ADI exhibited airway inflammation characterized by significantly elevated eosinophils and neutrophils, group AD only exhibited mild airway inflammation. Serum insulin levels were higher in groups ADI, AI and A. Immunohistochemistrical staining revealed a diffused distribution pattern of insulin receptor in the lung tissue. Positive cells infiltrating in the lung were increased significantly in groups A, AI and ADI. In groups induced diabetes the expression of insulin receptor mRNA was elevated. Conclusion Administration of low dose insulin aggravated airway inflammation to antigen provocation in rats. Insulin secretion was increased in the presence of inflammation. In the lung of antigen-challenged rats, insulin receptors on the surface of the infiltrating inflammatory cells and bronchial secretory cells were increased. 004 005 003 Saturday 5 April – Respiratory Nurses SIG Oral Presentations (1030–1200) Asthma A80 Respirology (2004) 9, (Suppl.)