支气管哮喘和慢性阻塞性肺疾病的异同

支气管哮喘（简称哮喘）和慢性阻塞性肺疾病（COPD）的关系一直是呼吸科关注和探讨的话题,二者在基因、病理、生理和临床等众多方面拥有许多异同.     

Systemic inflammation in chronic obstructive pulmonary disease and asthma: Similarities and differences

Background and objective:   While recent studies have shown that patients with COPD and patients with asthma exhibit evidence of airway and systemic inflammation, markers of systemic inflammation have not been compared between the two diseases.
Methods:   To evaluate circulating inflammatory markers, blood was sampled from 111 patients with COPD, 75 control subjects and 46 asthmatic patients (some of whom were smokers). Measurements of WCC, serum levels of fibrinogen, high-sensitivity (hs)-CRP, IL-8, IL-6, tumour necrosis factor-α (TNF-α), transforming growth factor (TGF)-β1, tissue inhibitors of metalloproteinase (TIMP)-1, neutrophil elastase and alpha1-antitrypsin (α1-AT) were performed.
Results:   Serum TNF-α, IL-6 and TIMP-1 concentrations were significantly higher in patients with stable COPD and patients with asthma than in control patients. Serum α1-AT levels were significantly higher in COPD patients than in asthmatic patients and control subjects, and serum TGF-β1 levels were higher in asthma patients than in COPD patients. Smoking status had no effect on markers in COPD and asthmatic patients.
Conclusions:   Although COPD and asthma share common markers of systemic inflammation, serum levels of TGF-β1 and α1-AT may reflect differences between the diseases.     

The similarities and differences of epidemic cycles of chronic obstructive pulmonary disease and asthma exacerbations

The majority of chronic obstructive pulmonary disease (COPD) and asthma exacerbations in both children and adults are associated with respiratory viral infections and are cyclic in nature. Some variation in these cycles is associated with the timing of the appearance of respiratory viruses, particularly influenza and respiratory syncytial virus. Much more, however, is associated with signal events that are of either fixed or predictable timing. In children, asthma exacerbations reach epidemic levels following school return after the summer vacation and these are predominantly associated with rhinovirus infections. Although younger adults experience a rise in asthma exacerbations at this time, these are secondary to the epidemic in children. Older adults with either COPD or asthma experience only a slightly elevated risk of exacerbations after school return, and hospital presentations for pneumonia in any age group show only marginal increases at that time. Exacerbations of both COPD and adult asthma, with increasing risk with age, are at their highest average annual levels during the Christmas period. This effect appears to be independent of the timing of above average levels of influenza, RSV, parainfluenza, or adenovirus detections; however, hospitalization for respiratory tract infections in all age groups reaches high levels at the same time. Both the post-summer vacation asthma epidemic and the Christmas epidemic of COPD, asthma, and pneumonia are synchronous with the timing of signal events, the day of school return for the former and Christmas Day for the latter, and have been for several years. The agents responsible for the Christmas epidemic of respiratory diseases have not yet been identified. The differences between age and disease exacerbation patterns after school return and at Christmas suggest that either different agents are involved or that the response to a common agent is different between the two signal events.     

Effect of corticosteroids on exacerbations of asthma and chronic obstructive pulmonary disease

Periodic exacerbations of disease severity, which may lead to hospitalization, are a characteristic feature of asthma and chronic obstructive pulmonary disease (COPD), becoming more prevalent as disease severity increases. Oral corticosteroids increase the rate of resolution of these episodes in both diseases. Inhaled corticosteroids are much less effective at conventional doses and are not recommended as a primary treatment for exacerbations of either disease. Maintenance therapy with inhaled corticosteroids significantly reduces the chance that a further exacerbation will occur in asthma. In general, increasing doses of inhaled corticosteroids are more effective than placebo therapy in preventing exacerbations, at least until patients become persistently symptomatic and regular users of inhaled corticosteroid therapy. Thereafter, the gains from doubling the dose of inhaled corticosteroid maintenance therapy are modest and generally inferior to those that result from adding other antiinflammatory or bronchodilator agents to the treatment regime. The reduction in the incidence of exacerbations with inhaled corticosteroids, compared with placebo, ranges from 15 to 20% in COPD versus almost 50% in severe asthma. However, given the impact of exacerbations on overall quality of life in COPD, even this modest reduction is likely to be clinically important.     

Current and future pharmacologic therapy of exacerbations in chronic obstructive pulmonary disease and asthma

Exacerbations are an important cause of the morbidity and mortality associated with asthma and chronic obstructive pulmonary disease. Newer therapies include long-acting beta(2)-agonists, which are more effective than short-acting bronchodilators. Inhaled corticosteroids and, in asthma, leukotriene receptor antagonists may have roles in the early phase of exacerbation as an alternative to or added to oral prednisolone. In the future, combinations of long-acting beta(2)-agonists and anticholinergic bronchodilators may offer additive clinical benefits. However, although the treatment and prevention of exacerbations of chronic obstructive pulmonary disease and asthma have been improved by using combinations of known therapies, further research addressing the underlying etiology as well as molecular and pathophysiologic mechanisms of exacerbation is needed to better target novel therapies to the appropriate patient populations and to develop new therapeutic strategies.     

Physiologic similarities and differences between asthma and chronic obstructive pulmonary disease

PURPOSE OF REVIEW: This review examines the physiologic mechanisms responsible for persistent maximum expiratory airflow limitation in nonsmoking patients with acute and chronic moderate to severe persistent asthma in comparison to chronic obstructive pulmonary disease. RECENT FINDINGS: The phenomenon of acute but reversible loss of lung elastic recoil during acute asthma is reviewed, although no plausible pathophysiologic explanation has been offered. Nonsmoking adults with stable asthma and persistent maximum expiratory airflow limitation, despite optimal polytherapy, were shown to have unsuspected and unexplained marked loss of lung elastic recoil in the absence of lung computed tomography scored emphysema. This condition resulted in up to 50% reduction in maximum expiratory airflow. Furthermore, these patients remain at high risk for adverse clinical events, including near-fatal asthma. In chronic obstructive pulmonary disease, reduction in maximum expiratory airflow is related to variable extent of loss of lung elastic recoil secondary to emphysema and concurrent intrinsic airway obstruction or obliteration of small airways. There is also an unexplained loss of lung elastic recoil in primary intrinsic small airways disease in the absence of emphysema. SUMMARY: Nonsmoking patients with moderate-severe persistent asthma and patients with smoking-related chronic obstructive pulmonary disease share similar physiologic mechanisms of expiratory airflow limitation, but probably caused by different anatomic abnormalities.     

Pathologic similarities and differences between asthma and chronic obstructive pulmonary disease

PURPOSE OF REVIEW: Classically, asthma and chronic obstructive pulmonary disease present distinct clinical, physiologic and pathologic features. However, not infrequently, patients may present with overlapping clinical symptoms and physiological abnormalities: patients with severe asthma may present with fixed airway obstruction and patients with chronic obstructive pulmonary disease may have hyperresponsiveness and eosinophilia. At pathological level, inflammatory and structural similarities also occur and may be related to the phenotypic overlaps. RECENT FINDINGS: In patients with asthma overlaps at inflammatory level exist with chronic obstructive pulmonary disease, such as increased neutrophilia in patients with severe asthma or an association of CD8+ T cells and lung-function decline. In chronic obstructive pulmonary disease, minimizing eosinophilia may be important to reduce exacerbations. Structural alterations occur in both diseases, but involving airway compartments differently. Airway epithelial changes, extracellular matrix deposition and mucus gland hypertrophy occur in both diseases. Asthmatics have thicker reticular basement membrane and more prominent smooth-muscle abnormalities, whereas emphysema is a distinct feature of chronic obstructive pulmonary disease. SUMMARY: Recognizing the differences and similarities at pathological level in both diseases may lead to a better understanding of the overlapping clinical and physiological phenotypes, thereby helping to better plan specific treatment and long-term management.     

N-acetylcysteine and exacerbations of chronic obstructive pulmonary disease

Oxidative stress may play a role in chronic obstructive pulmonary disease (COPD) exacerbations. There is heterogeneity in the literature with regard to the impact of antioxidant therapy on COPD exacerbation frequency. Clinical trials of N-acetylcysteine in COPD were identified in unrestricted searches of MEDLINE, CINAHL, International Pharmaceutical Abstracts and the Cochrane Register. Randomized, controlled trials which reported exacerbations over a treatment period > or =3 months were selected. Two observers independently extracted data regarding exacerbation number over the treatment period in subjects allocated to either N-acetylcysteine or placebo. Data were analyzed using inverse-variance weighted random effects meta-analysis methodology. Meta-analysis of data from 8 trials (randomized n = 2,214) indicated that N-acetylcysteine significantly reduced the odds of experiencing one or more exacerbations over the treatment period (odds ratio = 0.49, 95% confidence interval [0.32-0.74], p = 0.001). Treatment effect was not reduced in studies which enrolled >50% active smokers (odds ratio = 0.36 [0.24-0.55], p < 0.001), although a greater effect was observed with exclusion of subjects using concurrent inhaled corticosteroids (odds ratio = 0.42 [0.32-0.54], p < 0.0001), suggesting that inhaled steroids attenuate the effect of N-acetylcysteine. The use of N-acetylcysteine significantly reduces the odds of exacerbation in patients with COPD, an effect possibly attenuated by inhaled steroids but not smoking. This analysis suggests treatment with N-acetylcysteine may be beneficial in a subset of patients with COPD.     

Pathophysiology of exacerbations of chronic obstructive pulmonary disease

Smokers with stable chronic obstructive pulmonary disease have a chronic inflammation of the entire tracheobronchial tree characterized by an increased number of macrophages and CD8 T lymphocytes in the airway wall and of neutrophils in the airway lumen. Exacerbations of chronic obstructive pulmonary disease are considered to reflect worsening of the underlying chronic inflammation of the airways, caused mainly by viral and bacterial infections and air pollution. During exacerbations, the inflammatory cellular pattern changes, with a further increase of eosinophils and/or neutrophils and various inflammatory mediators--for example, cytokines (tumor necrosis factor-alpha, RANTES [regulated upon activation normal T cell-expressed and secreted], and eotaxin-1), chemokines (CXCL5 [ENA-78], CXCL8), chemokine receptors (CCR3, CXCR1, and CXCR2), adhesion molecules (E-selectin and ICAM-1), and markers of oxidative stress (H(2)O(2) and 8-isoprostane, glutathione depletion). Worsening of inflammation is considered responsible for the deterioration of lung function and clinical status during exacerbations.     

Risk factors of chronic obstructive pulmonary disease exacerbations

Chronic Obstructive Pulmonary Disease (COPD) is a chronic respiratory disease characterised by persistent respiratory symptoms and airflow limitation. COPD has a major impact on public health, mainly because of its increasing prevalence, morbidity and mortality. The natural course of COPD is aggravated by episodes of respiratory symptom worsening termed exacerbations that contribute to disease progression. Acute Exacerbations of COPD (AECOPD) can be triggered by a multitude of different factors, including respiratory tract infections, various exposures, prior exacerbations, non‐adherence to treatment and associated comorbidities. AECOPD are associated with an inexorable decline of lung function and a significantly worse survival outcome. This review will summarise the most important aspects regarding the impact of different factors that contribute to COPD exacerbations.     

Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease

The effects of broad-spectrum antibiotic and placebo therapy in patients with chronic obstructive pulmonary disease in exacerbation were compared in a randomized, double-blinded, crossover trial. Exacerbations were defined in terms of increased dyspnea, sputum production, and sputum purulence. Exacerbations were followed at 3-day intervals by home visits, and those that resolved in 21 days were designated treatment successes. Treatment failures included exacerbations in which symptoms did not resolve but no intervention was necessary, and those in which the patient's condition deteriorated so that intervention was necessary. Over 3.5 years in 173 patients, 362 exacerbations were treated, 180 with placebo and 182 with antibiotic. The success rate with placebo was 55% and with antibiotic 68%. The rate of failure with deterioration was 19% with placebo and 10% with antibiotic. There was a significant benefit associated with antibiotic. Peak flow recovered more rapidly with antibiotic treatment than with placebo. Side effects were uncommon and did not differ between antibiotic and placebo.     

Management of acute exacerbations in chronic obstructive pulmonary disease

An acute exacerbation of chronic obstructive pulmonary disease (COPD) is characterized by an acute worsening of symptoms accompanied by lung infection. In severe cases, an acute exacerbation may cause respiratory failure and death. Successful management of acute exacerbation of COPD in either the inpatient or outpatient setting requires attention to a number of key issues. In this review, issues regarding the management of acute exacerbations of COPD are discussed. An inhaled beta-2 agonist along with the inhaled anticholinergic bronchodilator are recommended. Antibiotic therapy has been demonstrated to improve clinical recovery and physical outcomes. It should be directed against the most commonly occurring pathogens and, in more severe cases, coverage against Gram-negative bacteria is considered. Short course of systemic steroids does provide benefit in hospitalized patients. Supplemental oxygen is appropriate for all patients with hypoxemia. Ventilatory support treatment may be necessary, noninvasive ventilatory assistance being preferable early in the course of the acute episode. In a high number of cases, endotracheal intubation may be avoided. Promoting smoking cessation and the use of influenzae and pneumococcal vaccination may help decrease frequency of episodes of these exacerbations.     

Inflammation and infection in exacerbations of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a common disorder with symptoms of chronic cough and progressive dyspnea caused by chronic bronchitis or emphysema. Acute exacerbations of COPD contribute to the accelerated decline in lung function characteristic of this disease and are associated with significant cost, morbidity, and mortality for patients. Controversy exists as to whether exacerbations are caused primarily by inflammation, infection, or perhaps a combination of both conditions. Advances in the pathogenesis of COPD have shed light on the role of inflammation in this condition and highlighted the differences in the inflammatory response present in COPD compared with asthma. Infectious agents often are suspected as causing acute exacerbations of COPD, and antibiotics are frequently prescribed empirically to patients. We review the evidence for an inflammatory and infectious etiology for exacerbations of COPD and compare and contrast how each impacts on this disease.     

Acute exacerbations and respiratory failure in chronic obstructive pulmonary disease

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) describe the phenomenon of sudden worsening in airway function and respiratory symptoms in patients with COPD. These exacerbations can range from self-limited diseases to episodes of florid respiratory failure requiring mechanical ventilation. The average patient with COPD experiences two such episodes annually, and they account for significant consumption of health care resources. Although bacterial infections are the most common causes of AECOPD, viral infections and environmental stresses are also implicated. AECOPD episodes can be triggered or complicated by other comorbidities, such as heart disease, other lung diseases (e.g., pulmonary emboli, aspiration, pneumothorax), or systemic processes. Pharmacologic management includes bronchodilators, corticosteroids, and antibiotics in most patients. Oxygen, physical therapy, mucolytics, and airway clearance devices may be useful in selected patients. In hypercapneic respiratory failure, noninvasive positive pressure ventilation may allow time for other therapies to work and thus avoid endotracheal intubation. If the patient requires invasive mechanical ventilation, the focus should be on avoiding ventilator-induced lung injury and minimizing intrinsic positive end-expiratory pressure. These may require limiting ventilation and "permissive hypercapnia." Although mild episodes of AECOPD are generally reversible, more severe forms of respiratory failure are associated with a substantial mortality and a prolonged period of disability in survivors.     

Structural and functional co-conspirators in chronic obstructive pulmonary disease exacerbations

Chronic obstructive pulmonary disease (COPD) exacerbations have a major impact on patients with COPD, yet they are complex events that are associated with a number of triggers and affected by the underlying disease process. A number of conditions can mimic the symptoms of an exacerbation and require evaluation. Airway and systemic inflammatory changes at exacerbation are modulated by infective factors (viruses and bacteria) and lead to the pathophysiologic effects seen at exacerbations with increase in airflow obstruction. Although bacteria or viruses can be isolated at exacerbation, often these organisms act in combination and lead to greater inflammatory changes and more severe exacerbation. Underlying structural changes such as radiologic changes of bronchiectasis that can be found in COPD can also modulate exacerbation severity and contribute to morbidity associated with exacerbations.