| Chronic Obstructive Pulmonary Disease (COPD) is defined physiologically by the presence of irreversible or partially reversible airway obstruction in patients with chronic bronchitis and/or emphysema. COPD is also the fourth most common cause of death in the world. Both the prevalence of and mortality from this disease have been increasing worldwide.More than 80% of COPD cases encountered in the Western world are related to tobacco smoke exposure. Occupational exposures and alphal antitrypsin deficiency are uncommon precedents for the development of COPD.Several potential contributions of bacterial infection to the etiology, pathogenesis, and clinical course of COPD can be identified. Though, the precise role of bacterial infection in COPD has been a source of controversy for several decades. Opinion regarding the contribution of bacteria to the pathogenesis of COPD has been Confirmed. Five potential pathways by which bacteria could contribute to the course and pathogenesis of COPD can be identified. (1) Childhood lower respiratory tract infection impairs lung growth, reflected in smaller lung volumes in adulthood. (2) Bacteria cause a substantial proportion of acute exacerbations of chronic bronchitis which cause considerable morbidity and mortality. (3) Chronic colonization of the lower respiratory tract by bacterial pathogens amplifies the chronic inflammatory response present in COPD and leads to progressive airway obstruction (vicious circle hypothesis). (4) Bacterial pathogens invade and persist in respiratory tissues, alter the host response to cigarette smoke, or induce a chronic inflammatory response and thus contribute to the pathogenesis of COPD. (5) Bacterial antigens in the lower airway induce hypersensitivity that enhances airway hyperreactivity and induces eosinophilic inflammation.Variation in the relative incidence of specific pathogens is seen and may relate to atient inclusion criteria and sputum culture techniques. The three predominant bacterial species isolated are nontypeable Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Other infrequently isolated potential pathogens are Haemophilus parainfluenzae, Staphylococcus aureus, Pseudomonas aeruginosa.Whether isolation from sputum of a potential pathogen represents infection of the lower airway causing the exacerbation episode has been a controversial issue for several decades. Several longitudinal cohort studies in the 1960s and 1970s demonstrated that the incidence of bacterial isolation from sputum during exacerbations of COPD was not different from the incidence during stable COPD. These studies also failed to demonstrate a higher bacterial titer in sputum during acute exacerbation than during stable COPD.H. parainfluenzae is present as part of the normal upper respiratory tract flora in humans. Therefore, the bacterium is frequently recovered from expectorated sputum from adults with COPD. The presence of H. parainfluenzae in the sputum of 2 to 27% of patients experiencing exacerbations has raised the question of whether H. parainfluenzae causes exacerbations of COPD. Bronchoscopy with the protected specimen brush performed during exacerbations has been used as a method to establish the etiology of some exacerbations in four recent studies. Bacteria were present in 50 to 72% of patients with exacerbations. Research recently studied the immune response to H. parainfluenzae in three patients with COPD and showed that these patients had higher titers of antibodies to H. parainfluenzae than healthy controls. Overall, there is simply not enough evidence at this time to state with any degree of confidence the role, if any, that H.parainfluenzae plays as a pathogen in COPD. one must examine the type of evidence which has established that H. influenzae and M. catarrhalis cause exacerbations.So we raise the question of whether H.parainfluenzae plays as a pathogen in COPD, whether and how H. parainfluenzae causes exacerbations of COPD.what is the etiolog,clinical characteristics of H. parainfluenzae lower respiratory tract infection. Part I The presence and antibiotic susceptibility of H. parainfluenzae in the sputum from adults with COPD of COPDand patients experiencing exacerbationsMethods:Sputa of patients of COPD were isolated and identified with ordinary agar and Improved Collumbia chocolate agar.Antibiotic sensitivity was determined. To compare the clinical characteristics of COPD patients who have Hpi infection. Antibiotic susceptibility testing was based on Kirby-Bauer disc diffusion technique. Theβ-lactamase was determined by nitrocefin paper disk method.Results:192 strains of H. parainfluenzae were taken from 1109 satisfactory sputum 17.3%). And 11 strains of H. parainfluenzae were isolated from 39 satisfactory sputum (28.2%) taken by bronchoscopy with the protected specimen brush performed during exacerbations.All isolates were Susceptible to Imipenem.The moxifloxacin, azithromycin, amoxicillin/clavulanic acid had better antibiotic action and the average drug resistance was lower than 5%. About 39.6%,33.3%,18.7%,21.9%isolates were resistant to ciprofloxacin, ampicillin sodium, streptomycin, levofloxacin.26.2%(38/126) of H. parainfluenzae isolated from patients producedβ-lactamase.Nine strains resisting to amplicilin wereβ-lactamase negative.Conclusions:1,The incidence of H. parainfluenzae infection was high in patients with severe COPD, this chronic infection contributes to the pathogenesis of COPD.2, These prevalent H. parainfluenzae strains were more resistant to ciprofloxacin, ampicillin sodium, streptomycin, levofloxacin. But Imipenem,moxifloxacin, azithromycin, amoxicillin/clavulanic acid is suitable for treating respiratory tract infections caused by HPi. In the patients with H. parainfluenzae infection, the higher drug resistance and the positive rate ofβ-lactamase of HPi should be paid attention to. Part II Serum strains-specific antibody response in patients with COPDMethods:Since antibody-mediated clearance of infecting organisms can succeed only in the presence of antibodies recognizing epitopes exposed by live bacteria, the potential functional significance of the antibody response to H. parainfluenzae in these patients was investigated by using intact bacteria isolated from their sputa to adsorb antibodies from their sera. We investigated the systemic antibody response in 39 patients with acute exacerbation of COPD.Patients' blood serum were collected at the beginning of the acute exacerbation,after four weeks and after six weeks respectively. The blood serum were diluted for the times. Serum strains-specific antibody were detected with indirect hemagglutination test,and results were analyzedResults and Conclusions:Results from the indirect hemagglutination test demonstrated that patients who were colonized with H. parainfluenzae had higher levels of serum strains-specific antibody for this organism than did negative control subjects. The specificity of the systemic immune response observed in our patients was therefore confirmed.PartⅢThe role of HPi in the pathogenesis of copd ratMethods:The animal model of COPD was established by intratrachel instillation of lipopolysaccharide (LPS) twice and passive smoking for two month. Animals were randomly divided into control and infection groups.The infection group rats received intratracheal instill of HPi,and control groups were given normal saline. Executed the rats at different time respectively, to observe the total and differential cell counts in bronchoalveolar lavage fluid(BALF) and the histopathological features; to measure the thickness of the airwaywall and the smoothmuscle layer of the small airway.Results:In the model animals, the number of goblet cells and the secretion of airway significantly increased than those in controls; The histology showed abundant inflammatory cells infiltrating the bronchia walls and lung tissue and the thickened airway walls and the accompanying arterioles with narrowed lumen; It also showed theruptured and enlarged alveoluse; The functional tests showed the increased airway resistance and the decreased compliance of respiratory system; the amount of neutrophils in BALF increased with positive correlation。Conclusions:H.parainfluenzae plays as a pathogen in COPD.In summary,our study showed that H.parainfluenzae plays as a pathogen in COPD. The higher drug resistance and the positive rate ofβ-lactamase of HPi should be paid attention to. |
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