The role of respiratory infection in exacerbation of chronic obstructive pulmonary disease

Periods of acute deterioration known as exacerbations significantly lower the quality of life and health status of patients with chronic obstructive pulmonary disease (COPD), thus making treatment of these patients more expensive. Understanding of the pathogenesis of COPD exacerbations and their influence on the clinical course and prognosis of this disease has greatly improved during the last decades. Some aspects of the interrelation between the infectious pathogen and the host organism have been studied. According to modern data, respiratory infections present one of the main causes of exacerbations of the disease. The role of respiratory viruses, especially rhinoviruses and respiratory syncytial virus, which often precede secondary bacterial infections, have been found to be important in the etiology of COPD exacerbation. The main bacterial etio-pathogens of COPD exacerbations--the non-capsulated bacteria H. influenzae, S. pneumoniae, and M. catarrhalis, which in 25 to 50% of cases colonize the lower respiratory tract (LRT)--have been isolated. Colonization of the LRT of infectious agents (viruses and bacteria) results in chronization of the inflammatory process and progress of the disease. Besides, colonization correlates with the severity of the disease. A "vicious circle" theory has been put forward to explain the pathogenesis of COPD exacerbations. Etiological diagnostics of a COPD exacerbation will allow adequate choice of effective etiotropic therapy making it possible to eradicate the pathogen or lower microbial load in the respiratory tract, which will decrease the risk of recurrence and improve the prognosis of the disease.     

双水平气道正压通气在慢性阻塞性肺疾病急性加重期患者中应用及效果

目的探讨双水平气道正压通气治疗慢性阻塞性肺疾病急性加重期临床疗效和安全性。方法选择2010年8月至2012年8月住院治疗的112例慢性阻塞性肺疾病急性加重期患者为研究对象,随机分为A组和B组,A组仅给予常规机械通气治疗,B组患者则给予不同时相应用双水平气道正压通气治疗,比较两组患者肺功能、血气分析、心率、呼吸频率、血压、机械通气时间、住院时间和住院费用等临床指标。结果 B组患者肺功能、血气分析、心率、呼吸频率、血压、机械通气时间、住院时间和住院费用均显著优于A组患者的,有显著性差异(P<0.05)。结论不同时相应用双水平气道正压通气治疗慢性阻塞性肺疾病急性加重期临床疗效确切,安全可靠,不良反应少。     

Comparison of once-daily cephalosporin regimens for community-acquired lower respiratory tract infections in patients with chronic lung disease

The efficacy of cefonicid and of ceftriaxone, administered once daily for the treatment of lower respiratory tract bacterial infections (pneumonia or bronchitis), was evaluated and compared in 118 patients with chronic lung disease. The patients were randomly assigned to receive 1 gm of either drug, intravenously or intramuscularly, daily for three to 11 days (mean, seven days). Pathogenic bacteria were isolated from sputum in 59% of patients; Haemophilus influenzae and Streptococcus pneumoniae predominated. Clinical cure or improvement was noted in 95% and 93% of patients treated with cefonicid and ceftriaxone, respectively, and bacteriologic cure or improvement in 69% and 81% (the differences were not significant). Side effects were infrequent and similar in the two treatment groups, except that diarrhea was more common in the ceftriaxone group (11%, versus 4.4% in the cefonicid group). It is concluded that patients with chronic lung disease who experience acute exacerbations associated with infection caused by H influenzae or S pneumoniae, or other susceptible organisms, can be effectively treated with once-daily administration of either cefonicid or ceftriaxone.     

Development of experimental respiratory infections in neutropenic rats with either penicillin-resistant Streptococcus pneumoniae or beta-lactamase-producing Haemophilus influenzae.

Acute respiratory infections with penicillin-resistant strains of Streptococcus pneumoniae and a beta-lactamase-producing strain of Haemophilus influenzae were established in neutropenic weanling rats. By use of nonsurgical intrabronchial instillation of the bacteria suspended in molten agar, reproducible, acute respiratory infections suitable for experimental antibiotic efficacy studies were established.     

Exacerbations of chronic obstructive pulmonary disease

Exacerbations of chronic obstructive pulmonary disease (COPD) cause morbidity, hospital admissions, and mortality, and strongly influence health-related quality of life. Some patients are prone to frequent exacerbations, which are associated with considerable physiologic deterioration and increased airway inflammation. About half of COPD exacerbations are caused or triggered primarily by bacterial and viral infections (colds, especially from rhinovirus), but air pollution can contribute to the beginning of an exacerbation. Type 1 exacerbations involve increased dyspnea, sputum volume, and sputum purulence; Type 2 exacerbations involve any two of the latter symptoms, and Type 3 exacerbations involve one of those symptoms combined with cough, wheeze, or symptoms of an upper respiratory tract infection. Exacerbations are more common than previously believed (2.5-3 exacerbations per year); many exacerbations are treated in the community and not associated with hospital admission. We found that about half of exacerbations were unreported by the patients, despite considerable encouragement to do so, and, instead, were only diagnosed from patients' diary cards. COPD patients are accustomed to frequent symptom changes, and this may explain their tendency to underreport exacerbations. COPD patients tend to be anxious and depressed about the disease and some might not seek treatment. At the beginning of an exacerbation physiologic changes such as decreases in peak flow and forced expiratory volume in the first second (FEV(1)) are usually small and therefore are not useful in predicting exacerbations, but larger decreases in peak flow are associated with dyspnea and the presence of symptomatic upper-respiratory viral infection. More pronounced physiologic changes during exacerbation are related to longer exacerbation recovery time. Dyspnea, common colds, sore throat, and cough increase significantly during prodrome, indicating that respiratory viruses are important exacerbation triggers. However, the prodrome is relatively short and not useful in predicting onset. As colds are associated with longer and more severe exacerbations, a COPD patient who develops a cold should be considered for early therapy. Physiologic recovery after an exacerbation is often incomplete, which decreases health-related quality of life and resistance to future exacerbations, so it is important to identify COPD patients who suffer frequent exacerbations and to convince them to take precautions to minimize the risk of colds and other exacerbation triggers. Exacerbation frequency may vary with the severity of the COPD. Exacerbation frequency may or may not increase with the severity of the COPD. As the COPD progresses, exacerbations tend to have more symptoms and take longer to recover from. Twenty-five to fifty percent of COPD patients suffer lower airway bacteria colonization, which is related to the severity of COPD and cigarette smoking and which begins a cycle of epithelial cell damage, impaired mucociliary clearance, mucus hypersecretion, increased submucosal vascular leakage, and inflammatory cell infiltration. Elevated sputum interleukin-8 levels are associated with higher bacterial load and faster FEV(1) decline; the bacteria increase airway inflammation in the stable patient, which may accelerate disease progression. A 2-week course of oral corticosteroids is as beneficial as an 8-week course, with fewer adverse effects, and might extend the time until the next exacerbation. Antibiotics have some efficacy in treating exacerbations. Exacerbation frequency increases with progressive airflow obstruction; so patients with chronic respiratory failure are particularly susceptible to exacerbation.     

Mechanisms of acute exacerbation of respiratory symptoms in chronic obstructive pulmonary disease

Exacerbations of chronic obstructive respiratory disease (ECOPD) are acute events characterized by worsening of the patient's respiratory symptoms, particularly dyspnoea, leading to change in medical treatment and/or hospitalisation. AECOP are considered respiratory diseases, with reference to the respiratory nature of symptoms and to the involvement of airways and lung. Indeed respiratory infections and/or air pollution are the main causes of ECOPD. They cause an acute inflammation of the airways and the lung on top of the chronic inflammation that is associated with COPD. This acute inflammation is responsible of the development of acute respiratory symptoms (in these cases the term ECOPD is appropriate). However, the acute inflammation caused by infections/pollutants is almost associated with systemic inflammation, that may cause acute respiratory symptoms through decompensation of concomitant chronic diseases (eg acute heart failure, thromboembolism, etc) almost invariably associated with COPD. Most concomitant chronic diseases share with COPD not only the underlying chronic inflammation of the target organs (i.e. lungs, myocardium, vessels, adipose tissue), but also clinical manifestations like fatigue and dyspnoea. For this reason, in patients with multi‐morbidity (eg COPD with chronic heart failure and hypertension, etc), the exacerbation of respiratory symptoms may be particularly difficult to investigate, as it may be caused by exacerbation of COPD and/or ≥ comorbidity, (e.g. decompensated heart failure, arrhythmias, thromboembolisms) without necessarily involving the airways and lung. In these cases the term ECOPD is inappropriate and misleading.     

慢性阻塞性肺疾病加重期细菌感染与痰颜色的关系

目的了解上海地区门、急诊慢性阻塞性肺疾病(COPD)急性加重期(AECB)患者气道的细菌感染情况,比较脓痰组、白粘痰组的痰中炎性细胞数与细菌阳性率,为临床诊治提供一定帮助。方法收集门、急诊COPD急性加重期患者159例痰液进行分离培养,并对痰颜色进行评分、炎症细胞计数与细胞分类检查,研究脓痰组、白粘痰组的痰中炎性细胞数与细菌阳性率的差异。结果共鉴定出致病菌92株(57.9%),主要为流感嗜血杆菌、肺炎克雷伯杆菌、铜绿假单胞菌。脓痰87份,细菌阳性率为82.7%;白粘痰72份,细菌阳性率27.8%,两组相比有显著差异(P<0.001)。脓痰白细胞总数显著高于白粘痰(P<0.001)。结论AECB患者脓痰中细菌阳性率较白粘痰显著增高,可以作为抗菌药物治疗指征,气道细菌感染导致中性粒细胞明显增高,痰颜色加深,气道炎症加重。     

Cefoperazone versus cefamandole in the treatment of acute bacterial lower respiratory tract infections

In a randomized comparative study, 113 patients were treated with cefoperazone or cefamandole for acute bacterial lower respiratory tract infections. Most patients had Streptococcus pneumoniae or Haemophilus influenzae infections, although five patients in the cefoperazone group had infections caused by other Gram-negative bacilli (two with Pseudomonas aeruginosa). The clinical responses and adverse effects were not significantly different between the two treatment groups. Satisfactory clinical responses occurred in 36/39 (92%) of evaluable patients in the cefoperazone group and 33/34 (97%) of evaluable patients treated with cefamandole. Two failures in the cefoperazone group were secondary to superinfection (Acinetobacter and Ps. aeruginosa). Bacteriological and symptomatic failure occurred in one patient with Ps. aeruginosa lung abscess treated with cefoperazone and in one patient with a polymicrobial empyema treated with cefamandole. The results of this study indicate that cefoperazone is safe and effective in the therapy of acute bacterial lower respiratory tract infections.     

The role of different microorganisms and infectious processes in the occurrence and course of bronchial asthma

The role of infection in bronchial asthma (BA) is unknown. The pathogenesis of BA contributes to the origin of infectious processes induced by different microorganisms. In view of the predominance of associations of viruses and bacteria in the etiology and pathogenesis of acute respiratory infections, it is difficult to define in vivo the share and role of these microorganisms which participate in the origin and enhancement of hypersensitivity, hyperreactivity and alterations in beta-adrenoreactivity. Some factors of bacterial pathogenicity promote BA progress. On contact with basophils and mast cells bacteria (both pathogenic ones and ordinary commensals) are capable of liberating histamine and other mediators during colonization of the bronchial tree and origin other infectious process. This mechanism of mediator liberation may contribute to the transformation of pre-asthma to BA or provoke its exacerbation.     

Evaluation of OPC-17116 against important pathogens that cause respiratory tract infections.

The antibacterial activity of OPC-17116, a new fluoroquinolone antibacterial agent, against important pathogens that cause respiratory tract infections was evaluated in vitro and in vivo and compared with those of ciprofloxacin, ofloxacin, and norfloxacin. The pharmacokinetic profiles of OPC-17116 were studied in both mice and rats given the drug orally at doses of 50 and 40 mg/kg of body weight, respectively. OPC-17116 showed a high degree of distribution in the lung tissues of both species, with maximum concentrations of 29.6 and 32.0 micrograms/g, respectively. Furthermore, the drug concentrations in lung tissue were about 10 to 15 times greater than the concentrations in plasma. OPC-17116 showed potent antibacterial activity against such pathogens as Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Haemophilus influenzae, and Moraxella catarrhalis. The MICs of this compound for 90% of these organisms except methicillin-resistant S. aureus and P. aeruginosa ranged from < or = 0.006 to 0.78 microgram/ml. The in vitro antibacterial activity of OPC-17116 was reflected by the efficacy of a single oral dose against systemic bacterial infections in mice. OPC-17116 showed a superior effect against gram-positive bacteria, H. influenzae, and M. catarrhalis. In comparison with the other reference compounds, the efficacy of OPC-17116 was less than that of ciprofloxacin against K. pneumoniae and P. aeruginosa. OPC-17116 showed a greater therapeutic effect than the other drugs against experimental acute pneumonia caused by these organisms in mice or rats. This excellent therapeutic effect against respiratory tract infections may be a result of its high level of distribution in lung tissue.     

支气管扩张急性加重期细菌谱及药敏谱调查

目的:了解支气管扩张患者急性加重期细菌谱及药敏谱情况,以指导临床合理使用抗菌药物治疗此类患者.方法:回顾性分析2009年1月至201 1年12月我院收治的支气管扩张急性加重患者146例人院时痰标本的细菌培养及药敏试验结果.结果:146例患者中分离到致病菌54例(37.0％);分离出无重复细菌56株,其中铜绿假单胞菌45株(80.4％),肺炎克雷伯菌、鲍曼不动杆菌、金黄色葡萄球菌、嗜麦芽窄食假单胞菌各2株,洋葱伯克霍尔德菌、流感嗜血杆菌、咽峡炎链球菌各1株.铜绿假单胞菌对常用的广谱β内酰胺类、庆大霉素、阿米卡星、环丙沙星的敏感率为71.1％～93.3％.结论:铜绿假单胞菌为引起支气管扩张急性加重的主要致病菌,初始经验性治疗可选择具有抗铜绿假单胞菌活性的广谱3内酰胺类、氨基糖苷类或氟喹诺酮类,并根据临床疗效和痰培养与药敏结果决定是否更改初始治疗药物.     

COPD exacerbations: causes, prevention, and treatment

The mechanisms of COPD exacerbation are complex. Respiratory viruses (in particular rhinovirus) and bacteria play a major role in the causative etiology of COPD exacerbations. In some patients, noninfective environmental factors may also be important. Data recently published from a large observational study identified a phenotype of patients more susceptible to frequent exacerbations. Many current therapeutic strategies can reduce exacerbation frequency. Future studies may target the frequent exacerbator phenotype, or those patients colonized with potential bacterial pathogens, for such therapies as long-term antibiotics, thus preventing exacerbations by decreasing bacterial load or preventing new strain acquisition in the stable state. Respiratory viral infections are also an important therapeutic target for COPD. Further work is required to develop new anti-inflammatory agents for exacerbation prevention, and novel acute treatments to improve outcomes at exacerbation.     

Specific serum IgE antibodies to bacterial antigens in allergic lung disease

A radio-allergosorbent test (RAST) to measure specific IgE antibodies in man to whole bacterial cells of Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae was developed to investigate different well-defined lung diseases (chronic bronchitis, allergic bronchopulmonary aspergillosis (ABPA), bronchial asthma allergic rhinitis, cystic fibrosis) and also in urticaria as compared with non-atopic blood donors. In addition, total IgE values and skin prick tests were assessed in these patients. The ABPA group gave the highest specific IgE RAST scores to all three bacteria, whilst the chronic bronchitis and cystic fibrosis groups also gave raised RAST scores with H. influenzae. There was a positive correlation between the patients' Sta. aureus and Str. pneumoniae immediate-type skin reactions and their RAST scores and total serum IgE concentrations, but there was only a low incidence of immediate-type skin test positivity to H. influenzae.     

Rhinovirus upper respiratory infection increases airway hyperreactivity and late asthmatic reactions.

Although viral upper respiratory infections (URIs) provoke wheezing in many asthma patients, the effect of these illnesses on the airway response to inhaled antigen is not established. The following study evaluated the effect of an experimental rhinovirus (RV) illness on airway reactivity and response to antigen in 10 adult ragweed allergic rhinitis patients. Preinfection studies included measurements of airway reactivity to histamine and ragweed antigen. Furthermore, the patients were also evaluated for late asthmatic reactions (LARs) to antigen (a 15% decrease in forced expiratory volume of the first second approximately 6 h after antigen challenge). 1 mo after baseline studies, the patients were intranasally inoculated with live RV16. All 10 patients were infected as evidenced by rhinovirus recovery in nasal washings and respiratory symptoms. Baseline FEV1 values were stable throughout the study. During the acute RV illness, there was a significant increase in airway reactivity to both histamine and ragweed antigen (P = 0.019 and 0.014, respectively). Before RV inoculation, only 1 of the 10 subjects had an LAR after antigen challenge. However, during the acute RV illness, 8 of 10 patients had an LAR (P less than 0.0085 compared with baseline); the development of LARs was independent of changes in airway reactivity and the intensity of the immediate response to antigen. Therefore, we found that not only does a RV respiratory tract illness enhance airway reactivity, but it also predisposes the allergic patient to develop LARs, which may be an important factor in virus-induced bronchial hyperresponsiveness.     

COPD: management of acute exacerbations and chronic stable disease

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are treated with oxygen (in hypoxemic patients), inhaled beta2 agonists, inhaled anticholinergics, antibiotics and systemic corticosteroids. Methylxanthine therapy may be considered in patients who do not respond to other bronchodilators. Antibiotic therapy is directed at the most common pathogens, including Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Mild to moderate exacerbations of COPD are usually treated with older broad-spectrum antibiotics such as doxycycline, trimethoprim-sulfamethoxazole and amoxicillin-clavulanate potassium. Treatment with augmented penicillins, fluoroquinolones, third-generation cephalosporins or aminoglycosides may be considered in patients with more severe exacerbations. The management of chronic stable COPD always includes smoking cessation and oxygen therapy. Inhaled beta2 agonists, inhaled anticholinergics and systemic corticosteroids provide short-term benefits in patients with chronic stable disease. Inhaled corticosteroids decrease airway reactivity and reduce the use of health care services for management of respiratory symptoms. Preventing acute exacerbations helps to reduce long-term complications. Long-term oxygen therapy, regular monitoring of pulmonary function and referral for pulmonary rehabilitation are often indicated. Influenza and pneumococcal vaccines should be given. Patients who do not respond to standard therapies may benefit from surgery.     

Serum ECP and MPO are increased during exacerbations of chronic bronchitis with airway obstruction.

Many studies have demonstrated that, in asthma, serum levels of eosinophil cationic protein (ECP) are related to the activity and severity of the disease and can be used to evaluate the response to steroid treatment. During exacerbations of chronic bronchitis, airway inflammation shows some features of asthmatic inflammatory processes, with recruitment of eosinophils and recovery of significant amounts of ECP in bronchial lavage fluid (BAL). Involvement of neutrophils, with high levels of myeloperoxidase (MPO), is, on the contrary, typical of this latter disease, and not shared with asthma. In spite of the information collected with BAL and bronchial biopsy studies, few data still exist on serum levels of these proteins in chronic bronchitis. The objective of this study was to assess if serum levels of ECP and MPO are specifically increased in exacerbations of chronic bronchitis, as compared to other non-asthmatic acute respiratory disturbances. Serum ECP, MPO and immunoglobulin E (IgE) levels were measured in 17 non-atopic patients with exacerbation of chronic bronchitis with airway obstruction (COPD) and in 11 control subjects seeking emergency medical treatment for unrelated acute respiratory problems. Spirometry was performed in patients able to give the necessary collaboration. All the subjects of this study were recruited from the emergency department. Both ECP and MPO were significantly increased in serum from patients with exacerbated COPD (22.2 +/- 4.1 vs 9.5 +/- 1.4 mcg/L and 853 +/- 168 vs 375 +/- 41 mcg/L) and a strong correlation existed between these two variables (r = 0.782). A further control group was made of 11 patients with stable COPD. These subjects had levels of both ECP (13.1 +/- 2.7 mcg/L) and MPO (469 +/- 71) significantly lower than patients with exacerbated disease and higher than those without COPD. We conclude that serum ECP and MPO are increased during the exacerbations of COPD. These observations can give a basis for further studies aimed to evaluate the utility of these two proteins as markers of activity and severity of COPD.     

A resuscitated case from asphyxia by large bronchial cast

A 62-year-old woman with bronchiectasis suffered from asphyxia due to a large bronchial cast that obstructed the bronchial tree. Immediate bronchoscopic suction of a bronchial cast of 17 cm in length through the intubated tube relieved the patients without any complications. Large bronchial casts appear to be rare in this century but it should be considered in patients with acute exacerbation of excessive sputa not only in patients with asthma or allergy but also in patients with respiratory tract infection.     

支气管哮喘患者血清嗜酸细胞趋化因子水平的变化及意义

目的探讨嗜酸细胞趋化因子(Eotaxin)在支气管哮喘发病中的作用。方法选择我院呼吸内科门诊就诊的哮喘患者76例,按病程分为哮喘急性发作组25例,哮喘持续组27例,哮喘缓解组24例;选择同期在我院体检的健康志愿者28例设为健康对照组。所有研究对象均行肺功能检测及外周血嗜酸细胞(Eos)计数和血清Eotaxin水平测定并进行比较。结果哮喘急性发作组、哮喘持续组外周血Eos计数及血清Eotaxin水平明显高于哮喘缓解组和健康对照组,哮喘缓解组外周血Eos计数及血清Eotaxin水平明显高于健康对照组,差异均有统计学意义(P<0.05)。哮喘急性发作组、哮喘持续组、哮喘缓解组血清Eotaxin水平与其外周血Eos计数呈正相关(r=0.592,0.598,0.584;P=0.031,0.033,0.029),与最大呼气流速改变率(ΔPEF%)呈正相关(r=0.589,0.591,0.585;P=0.035,0.041,0.042),与第一秒用力呼气容积(FEV1)占预计值百分比呈负相关(r=-0.582,-0.576,-0.569;P=0.042,0.044,0.039)。结论支气管哮喘患者血清Eotaxin水平明显升高,并与肺功能受累情况及气道高反应性显著相关,Eotaxin是参与哮喘气道炎性反应过程的重要因子。     

Sultamicillin--a new antibiotic in the treatment of persistent lower respiratory tract infections caused by Haemophilus influenzae

Haemophilus influenzae is a frequent cause of recurrent or chronic lower respiratory tract infections in patients suffering from cystic fibrosis (CF) and other chronic obstructive pulmonary disease (COPD). Ampicillin and its derivatives are routinely used in treatment, but resistant strains producing beta-lactamase frequently necessitate the use of other antibiotics. Sultamicillin is a compound agent for oral use in which ampicillin and the beta-lactamase inhibitor sulbactam are linked as a double ester. This combination is active in vitro against many beta-lactamase producing bacteria including ampicillin-resistant H. influenzae. Eight CF children and ten children with other COPD suffering from chronic or recurrent H. influenzae infection of the lower respiratory tract were treated with sultamicillin orally, 25 mg/kg, 12-hourly, for two weeks. Nine infections were caused by ampicillin-resistant strains. At the end of the treatment 65% of the patients were free of H. influenzae. The only adverse reaction was diarrhoea which occurred in 14 patients, and necessitated withdrawal of one patient from the study.     

The clinical efficacy of treating patients with nonspecific lung diseases using low-energy laser irradiation and intrapulmonary drug administration]

Intrapulmonary administration of glucocorticosteroids and antibiotics combined with low-energy laser radiation was employed in the treatment of patients with infection-dependent bronchial asthma in the phase of exacerbation and frequent asphyxia attacks, long medical history and of patients with lung abscesses. The purpose of the work was to study and compare the clinical effectiveness of the method in the gravest group of patients suffering from nonspecific pulmonary diseases: suppurative (acute lung abscess) and infectious allergic (infection-dependent bronchial asthma of medium gravity with frequent attacks, long medical history, tendency towards aggravation of the status and low efficacy of broncholytics). The results of the treatment and follow-up have shown that the use of the combined treatment suggested is most optimal in patients with acute lung abscesses (the percentage of the cured is 94.1). In patients with infection-dependent bronchial asthma, the use of laser therapy combined with intrapulmonary administration of steroids also noticeably improved the clinical, functional and immunological characteristics, prolonged the phase of remission.