Airway inflammation in asthma and chronic obstructive pulmonary disease with special emphasis on the antigen-presenting dendritic cell: influence of treatment with fluticasone propionate

Asthma is a chronic inflammatory disorder of the airways characterized by variable airflow limitation and airway hyperresponsiveness. The type of inflammatory response in asthma is compatible with a major contribution of professional antigen-presenting cells. The airways in chronic obstructive pulmonary disease (COPD) are also markedly inflamed; however, the predominant types of inflammatory cells and the main anatomical site of the lesion appear to differ from those in asthma. COPD is characterized by reduced maximum expiratory flow and slow forced emptying of the lungs. Steroids are the most prominent medication used in the treatment of asthma and COPD; however, the beneficial effect of steroid treatment in COPD is subject of debate. We investigated the efficacy of fluticasone propionate (FP) treatment in atopic asthmatics and in COPD patients with bronchial hyperreactivity who smoke. The effect of the treatment on bronchial hyperreactivity and indices of the methacholine dose–response curve were analysed, as well as indices of inflammation of the airway mucosa with special emphasis on the antigen presenting dendritic cell. Treatment of allergic asthmatic patients resulted in improvement of lung function (FEV₁), a decrease in bronchial hyperresponsiveness and a decrease of maximal airway narrowing. During the FP-treatment of COPD patients, FEV₁ remained stable, while FEV₁ deteriorated significantly in the placebo group. Therefore, steroid treatment may have a beneficial effect in COPD patients with bronchial hyperresponsiveness (BHR). Since immunohistochemical analysis of bronchial biopsy specimens from asthma and COPD patients show disease-specific aspects of inflammation, the anti-inflammatory effect of FP is obtained through modulation of different cell populations in asthma and COPD.     

Asthma and COPD

The two obstructive airway diseases bronchial asthma and chronic obstructive pulmonary disease (COPD) represent major global causes of disability and death, and COPD is estimated to become the third most common cause of death by 2020. The structural and pathophysiologic findings in both diseases appear to be easily differentiated in the extremes of clinical presentation. However, a significant overlap may exist in individual patients regarding features such as airway wall thickening on computer tomography or reversibility and airway hyperresponsiveness in lung function tests. Airway inflammation differs between the two diseases. In bronchial asthma, airway inflammation is characterized in most cases by an increased number of activated T-lymphocytes, particularly CD4+ Th2 cells, and sometimes eosinophils and mast cells. The most notable difference of chronic severe asthma compared with mild to moderate asthma is an increased number of neutrophils. In stable COPD, airway inflammation is characterized by an increased number of T-lymphocytes, particularly CD8+ T cells, macrophages and neutrophils. With the progression of the disease severity, macrophage and neutrophil numbers increase. Although there may be a partial overlap between asthma and COPD in some patients, the differences in functional, structural and pharmacological features clearly demonstrate the consensus that asthma and COPD are different diseases along all their stages of severity.     

Phenotyping airways disease: an A to E approach

The airway diseases asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous conditions with overlapping pathophysiological and clinical features. It has previously been proposed that this heterogeneity may be characterized in terms of five relatively independent domains labelled from A to E, namely airway hyperresponsiveness (AHR), bronchitis, cough reflex hypersensitivity, damage to the airways and surrounding lung parenchyma, and extrapulmonary factors. Airway hyperresponsiveness occurs in both asthma and COPD, accounting for variable day to day symptoms, although the mechanisms most likely differ between the two conditions. Bronchitis, or airway inflammation, may be predominantly eosinophilic or neutrophilic, with different treatments required for each. Cough reflex hypersensitivity is thought to underlie the chronic dry cough out of proportion to other symptoms that can occur in association with airways disease. Structural changes associated with airway disease (damage) include bronchial wall thickening, airway smooth muscle hypertrophy, bronchiectasis and emphysema. Finally, a variety of extrapulmonary factors may impact upon airway disease, including rhinosinusitis, gastroesophageal reflux disease, obesity and dysfunctional breathing. This article discusses the A to E concept in detail and describes how this framework may be used to assess and treat patients with airway diseases in the clinic.     

Diagnosis of asthma and chronic obstructive pulmonary disease in general practice.

There may be an overlap between the clinical pictures of asthma and chronic obstructive pulmonary disease which hampers a clear distinction between the two diseases. Most symptoms presented by patients do not clearly belong exclusively to either asthma or chronic obstructive pulmonary disease. By the nature of their discipline and training, general practitioners focus mainly on symptoms presented, which do not give a decisive answer in the differential diagnosis between the two diseases. Therefore, general practitioners must rely on objective parameters, such as determining the presence and degree of reversibility of airway obstruction, diurnal peak flow variability, bronchial hyper-responsiveness and allergy. This paper puts forward a pragmatic, primary care definition of asthma and chronic obstructive pulmonary disease.     

Function and mechanisms of TSLP/TSLPR complex in asthma and COPD

Thymic stromal lymphopoietin (TSLP) is a key pro-allergic cytokine that has recently been linked to chronic airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). High levels of TSLP were detected in bronchial mucosa of asthma and COPD patients suggesting TSLP's biological role beyond a signature 'Th2-favoring' or 'pro-allergic cytokine'. Besides inflammatory cells, airway structural cells produce and are targets of TSLP suggesting a potential autocrine loop that may have a profound effect on local inflammatory response and airway remodelling. This review sums up diverse mechanisms that mediate TSLP/TSLP receptor-signalling network in chronic airway diseases.     

Airways reactivity in patients with CF

Airways reactivity, hyper-reactivity, and hyper-responsiveness are terms used to describe airways for which there appears to be increased bronchial smooth muscle tone or responsiveness. Some patients with cystic fibrosis (CF) have concomitant asthma causing airway hyperresponsiveness as manifested by recurrent acute symptoms of dyspnea that is impressively responsive to an inhaled beta 2 agonist and/or systemic corticosteroids. However, many others have a degree of bronchodilator responsiveness in the absence of an impressive clinical response to such anti-asthmatic treatment. In contrast to those with asthma, exercise does not induce bronchospasm and can even cause bronchodilatation in patients with CF who have bronchodilator responsiveness in the absence of asthma. The airway hyperresponsiveness of CF also differs in its response to histamine induced bronchospasm which is effectively reversed with ipratropium in patients with CF who symptomatically do not have asthma, whereas ipratropium does not adequately reverse histamine-induced bronchospasm in those with concomitant symptoms of asthma. These and other data suggest that the increased airway reactivity in patients with CF is vagally mediated and results from the airway damage caused by the lung disease. The use of bronchodilators as a routine part of CF lung disease care is controversial, but there is little evidence that treating airway reactivity in patients with CF is of clinical importance as a routine measure in the absence of clinical asthma. Definite subjective improvement in symptoms or improved sputum production when a bronchodilator precedes chest physical therapy should be sought to justify continued use in individual patients.     

Airway inflammation and hyperresponsiveness to adenosine 5'-monophosphate in chronic obstructive pulmonary disease

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is often accompanied by bronchial hyperresponsiveness (BHR). Measurement of BHR may give information about airway inflammation. OBJECTIVE: To investigate the role of airway inflammation in hyperresponsiveness to adenosine 5'-monophosphate (AMP) in COPD. METHODS: We investigated inflammatory indices in induced sputum, bronchoalveolar lavage (BAL) fluid and bronchial biopsies in subjects with COPD with and without hyperresponsiveness to AMP. Twelve nonatopic subjects with COPD with hyperresponsiveness to AMP (mean +/- SD, age 63 +/- 8 years, FEV1% predicted 56 +/- 13%), six without BHR (age 60 +/- 6 years, FEV1% predicted 65 +/- 11%) and 11 healthy nonatopic controls without BHR (age 58 +/- 8 years, FEV1% predicted 104 +/- 11%) participated in the study. RESULTS: Subjects with COPD with BHR had significantly higher numbers of mucosal CD8 + and higher percentages of sputum eosinophils than those without BHR (median, 550 cells/mm2; range, 30-1340 vs 280 cells/mm2; range, 110-450, P = 0.045; and median, 2.7%; range, 0.5-8.5 vs 0.6%; range, 0-0.8 %, P = 0.0036, respectively). No differences were observed in BAL fluid. CONCLUSION: We conclude that hyperresponsiveness to AMP in COPD is associated with airway inflammation that is characterized by increased numbers of mucosal CD8 + cells and percentages of sputum eosinophils. Hyperresponsiveness to AMP may be used as a marker of airway inflammation in COPD, but its significance in the clinical course remains to be determined.     

Protective effect of oral terfenadine and not inhaled ipratropium on adenosine 5'-monophosphate-induced bronchoconstriction in patients with COPD

BACKGROUND: Inhalation of adenosine 5'-monophosphate (AMP) causes bronchoconstriction in patients with asthma and in many patients with chronic obstructive pulmonary disease (COPD). In asthma, AMP-induced bronchoconstriction has been shown to be determined mainly by release of mast cell mediators, and possibly by vagal nerve stimulation, since oral terfenadine (H1-receptor antagonist) and inhaled ipratropium bromide (muscarinic receptor antagonist) both increase PC20AMP. OBJECTIVE: To investigate the mechanism of AMP-induced bronchoconstriction in COPD. METHODS: We performed a randomized, double-blind, placebo-controlled, crossover trial. Forty-four nonatopic hyperresponsive smokers with COPD (mean age +/- SD: 60+/-7 years, FEV1 61+/-12% of predicted and FEV1/VC 51+/-8%, geometric mean [GM] PC20methacholine 0.62 mg/mL and GM PC20AMP 6.77 mg/mL) participated. PC20methacholine and PC20AMP were assessed on 3 days. Before the challenges they used either 180 mg of oral terfenadine, 120 microg of inhaled ipratropium bromide, or placebo. RESULTS: GM PC20AMP was 5.44 mg/mL after placebo, increasing with 0.9 doubling concentration (P<0.0001) after terfenadine and decreasing 0.3 doubling concentration after ipratropium bromide (NS). GM PC20methacholine was 0.75 mg/mL after placebo, increasing 0.4 doubling concentration after terfenadine (NS) and 3 doubling concentrations after ipratropium bromide (P<0.0001). CONCLUSION: These findings indicate that histamine release is important in the pathophysiology of AMP-induced bronchoconstriction in smokers with COPD, whereas vagal nerve stimulation does not play a role. Therefore, PC20AMP may be a valuable tool in evaluation of treatments which affect airway histamine release.     

Effect of cigarette smoke exposure in vivo on bronchial smooth muscle contractility in vitro in rats

Cigarette smoking is a risk factor for the development of airway hyperresponsiveness and chronic obstructive pulmonary disease. Little is known concerning the effect of cigarette smoking on the contractility of airway smooth muscle. The current study was performed to determine the responsiveness of bronchial smooth muscles isolated from rats that were subacutely exposed to mainstream cigarette smoke in vivo. Male Wistar rats were exposed to diluted mainstream cigarette smoke for 2 h/d every day for 2 wk. Twenty-four hours after the last cigarette smoke exposure, a marked airway inflammation (i.e., increases in numbers of neutrophils, lymphocytes, and macrophages in bronchoalveolar lavage fluid and peribronchial tissues) was observed. In these subacutely cigarette smoke-exposed animals, the responsiveness of isolated intact (nonpermeabilized) bronchial smooth muscle to acetylcholine, but not to high K+ -depolarization, was significantly augmented when compared with the air-exposed control group. In alpha-toxin-permeabilized bronchial smooth muscle strips, the acetylcholine-induced Ca2+ sensitization of contraction was significantly augmented in rats exposed to cigarette smoke, although the contraction induced by Ca2+ was control level. Immunoblot analyses revealed an increased expression of RhoA protein in the bronchial smooth muscle of rats that were exposed to cigarette smoke. Taken together, these findings suggest that the augmented agonist-induced, RhoA-mediated Ca2+ sensitization may be responsible for the enhanced bronchial smooth muscle contraction induced by cigarette smoking, which has relevance to airway hyperresponsiveness in patients with chronic obstructive pulmonary disease.     

Correlation between increased bronchial responsiveness to histamine and diminished plasma cyclic adenosine monophosphate response after epinephrine in asthmatic children. Diminished plasma cyclic adenosine monophosphate response after epinephrine in moderate childhood asthma.

The respiratory threshold to histamine and the plasma cyclic adenosine monophosphate (AMP) every 5 min for 40 min after subcutaneous epinephrine were determined in 21 children with moderate bronchial asthma who were without symptoms at the time of study. There was a statistically significant correlation between a high respiratory sensitivity to histamine and a low plasma cyclic AMP response to epinephrine. The plasma cyclic AMP response was compared with that in 16 control subjects. The asthmatic patients had significantly diminished responses; the difference was greatest for the values 25 min after stimulation. This study supports the hypotheses that the bronchial hyperresponsiveness in asthma is due partly to a defective beta adrenergic system and that the defect is permanent, existing also during periods without symptoms or medication and in patients with moderate asthma.     

Tumor necrosis factor in sputa of patients with bronchial asthma on exacerbation

TNF is a cytokine recently implicated as an important inflammatory mediator. TNF concentrations in sputa from 13 patients with bronchial asthma on exacerbation and 12 patients with chronic obstructive pulmonary disease were measured. After sonication, the sputa were centrifuged. The supernatants were assayed for the presence of TNF by use of an enzyme-linked immunosorbent assay. TNF was detected in all patients with bronchial asthma (1783 +/- 420 pg/ml), while low values of TNF were detected in only 5 of the 12 COPD patients. It is suggested that TNF is involved in airway inflammation in bronchial asthma.     

Surfactant protein D inhibits early airway response in Aspergillus fumigatus-sensitized mice

BACKGROUND: The surfactant protein SP-D has been reported to reduce bronchial hyper-responsiveness, blood eosinophilia, and T-helper type 2 cytokines in models of allergic asthma. However, little is known about the functional effect of SP-D on the early airway response upon allergen inhalation, which is an important feature of this disease. OBJECTIVE: We investigated whether SP-D is able to reduce the immediate allergen-induced mediator release and the early bronchial obstruction in addition to its effects on airway inflammation and bronchial hyperresponsiveness in an Aspergillus fumigatus mouse asthma model. METHODS: A. fumigatus-sensitized mice were treated with a recombinant fragment of human SP-D or placebo. Lung functions were measured in orotracheally intubated, spontaneously breathing animals using body plethysmography. In addition, passively sensitized precision-cut lung slices (PCLS) were used to determine the effect of SP-D on allergen-induced histamine release. RESULTS: SP-D inhibited the allergen-induced early airway response and reduced airway hyperresponsiveness compared with placebo. Eosinophilia in bronchoalveolar lavage and lung tissue was reduced after SP-D treatment, possibly by reducing eotaxin levels in the lung. Furthermore, SP-D treatment reduced the allergen-induced histamine release from PCLS. CONCLUSION: These data suggest that SP-D not only reduces allergen-induced eosinophilic inflammation and airway hyperresponsiveness but also provides protection against early airway obstruction by inhibition of early mediator release.     

运动-组胺激发试验对提高支气管哮喘诊断价值的研究

目的　探讨运动 -组胺激发试验 (EHIA)对支气管哮喘的诊断价值 .方法　对 2 0例健康者、118例支气管哮喘、2 2例过敏性鼻炎、2 4例慢性支气管炎患者进行运动 -组胺激发试验 ,并与单纯运动激发试验及组胺激发试验进行比较 .结果　显示运动 -组胺激发试验对哮喘患者的诊断阳性率达 97.4%、特异性 10 0 % ,且EHIA阳性所吸入的组胺量也反映了哮喘患者非特异性气道高反应性 .结论　运动 -组胺激发试验对提高早期及非典型支气管哮喘的确诊具有实用价值     

Provoked models of asthma: what have we learnt?

Asthma is a chronic inflammatory disease of the airways characterized by physiological abnormalities of variable airflow obstruction and airway hyperresponsiveness (AHR) to a wide variety of physical and inhaled chemical stimuli and the presence of symptoms. AHR is measured by challenging the airways with a variety of agonists and naturally occurring stimuli, which results in constriction of the airway smooth muscle, leading to airway narrowing and airflow limitation. There are two distinct mechanisms by which the airways can narrow to a constrictor stimulus and these are defined by the pathways they take to induce AHR. Direct stimuli are pharmacological agents administered exogenously (such as histamine or methacholine) that act 'directly' on specific receptors on the bronchial smooth muscle to cause constriction. The other mechanism by which the airway can narrow is via the inhalation of indirect stimuli, which include natural stimuli, such as allergen or exercise, and pharmacological agents such as adenosine monophosphate and hyper-osmotic agents (e.g. hypertonic saline or dry powder mannitol). These stimuli induce airway narrowing 'indirectly' by causing the endogenous release of mediators of bronchoconstriction from airway inflammatory cells. Provoked models of asthma have been extremely valuable in understanding the pathobiology of asthma, in aiding diagnosis, in helping to clarify the mechanisms of actions of effective drugs and in the development of new entities to treat asthma. Some provoked models are valuable clinically, particularly those that measure direct AHR, while others, particularly allergen challenge, have been used in animal models and in humans to study the mechanisms of allergen-induced airway inflammation and the associated physiological changes, as well in the development of new drugs for asthma. An emerging role for measurements of AHR is in the evaluation of the optimal treatment for patients with asthma.     

Airway function correlates with circulating eosinophil, but not mast cell, markers of inflammation in childhood asthma

Background Lung function tests, including forced expiratory volume in one second (FEV₁), forced expiratory flow at 25–75% of vital capacity (FEF_25–75%) and provocation concentrations of histamine which reduce FEV] by 20% (PC₂₀), are used as indicators of airway form and function in bronchial asthma. Recently, markers of eosinophil activation in bronchial lavage and serum have been suggested as a measure of eosinophil mediated inflammation in the airways. These include eosinophil cationic protein (ECP), eosinophil protein X (EPX) (also known as eosinophil derived neuro-toxin) and eosinophil peroxidase (EPO). Similarly, serum tryptase has been used as a marker of mast cell activation in systemic anaphylaxis. Objectives We measured both sets of indices in a group of children with moderately severe asthma to assess the contribution of eosinophil and mast cell mediated events to airflow limitation and bronchial hyperresponsiveness. Methods Forty-eight children aged 5–10 years had spirometric assessments, histamine challenges and blood sampling on the same occasion. After analysis of sera, the indices were compared. Results The eosinophil markers ECP and EPX correlated very well with each other. They showed a moderate negative correlation with PC₂₀ for histamine. EPX was also found to negatively correlate with FEV, and FEF_25–75%. Serum tryptase levels showed no such correlates with airway function. Conclusion These results suggest that serum markers of eosinophil activation correlate with airway function in childhood asthma, and may be of value in assessing the severity of the disease. It further supports the notion that childhood asthma has a similar immunopathology to that occurring in adults, with predominance of eosinophil mediated inflammation.     

Diagnostic accuracy of sputum outcomes in chronic stable asthma

BACKGROUND: Asthma with non-remitting airflow obstruction may not always be differentiated from COPD with airway hyperreactivity. Many attempts have been made to find useful markers for the distinction between these two disorders. OBJECTIVE AND METHODS: In order to help the finding of a useful marker for the diagnosis of asthma in the population of patients with airway obstruction we analysed the diagnostic accuracy of sputum eosinophils and sputum ECP in 91 patients with asthma, 15 patients with chronic bronchitis, 32 patients with chronic obstructive pulmonary disease (COPD) and 20 controls subjects, by performing ROC analysis. RESULTS: Sputum eosinophils were above the normal range of our laboratory (0-3.7%) in 48 asthma patients and in six COPD patients, while sputum ECP (normal range < 85 microg/L) was high in 65 asthma patients, in 24 COPD patients and in nine chronic bronchitis patients. The ROC analysis revealed that sputum eosinophils count (AUC = 0.82) was more accurate than both sputum ECP levels (AUC = 0.56) (P < 0.0001) and beta2-reversibility (AUC = 0.53) (P = 0.0001) in differentiating asthmatic from non-asthmatic subjects (COPD, chronic bronchitis patients and normal subjects). The diagnostic accuracy of ECP was similar to that of bronchial reversibility (P = 0.76). When ROC analysis was performed by including only patients with airway obstruction (36 asthmatics with airway obstruction and COPD patients), both eosinophil count (AUC = 0.77) and beta2-reversibility (AUC = 0.66) were more accurate than ECP measurement (AUC = 0.39) in discriminating asthmatics from COPD patients (P < 0.00001 and P = 0.04, respectively). CONCLUSION: Sputum eosinophils seem to be valid markers for detecting asthma in a population of patients with airway obstruction. Moreover, the higher diagnostic accuracy of eosinophils in the sputum compared to sputum ECP and bronchial reversibility reinforces the role of cytological analysis of sputum in the diagnosis of chronic stable bronchial asthma.     

Defensins: key players or bystanders in infection, injury, and repair in the lung?

Antimicrobial peptides have been identified as key elements in the innate host defense against infection. Recent studies have indicated that the activity of antimicrobial peptides may be decreased in cystic fibrosis, suggesting a major role for these peptides in host defense against infection. One of the most intensively studied classes of antimicrobial peptides are defensins. Defensins comprise a family of cationic peptides that in human subjects can be divided into the alpha- and beta-defensin subfamilies. The alpha-defensins are produced by neutrophils and intestinal Paneth's cells, whereas beta-defensins are mainly produced by epithelial cells. Although studies on beta-defensins have so far focused on their antimicrobial activity, studies on alpha-defensins have suggested a role of these peptides in inflammation, wound repair, and specific immune responses. alpha-Defensins, which accumulate in airway secretions of patients with various chronic inflammatory lung disorders, were shown to be cytotoxic toward airway epithelial cells and to induce chemokine secretion in several cell types. Furthermore, the capacity of alpha-defensins to promote bacterial adherence to epithelial cells in vitro further supports a role for these peptides in the pathogenesis of chronic obstructive pulmonary disease and cystic fibrosis. Increased numbers of neutrophils are also present in the airways of patients with asthma, suggesting that neutrophils are involved in the pathogenesis of this disease. Because defensins are able to induce histamine release by mast cells and increase the airway hyperresponsiveness to histamine, it is tempting to speculate that defensins may also contribute to the inflammatory processes in asthma. Besides these proinflammatory effects, alpha-defensins may also display anti-inflammatory activities, including regulation of complement activation and proteinase inhibitor secretion. Finally, defensins may be involved in wound repair because defensins increase epithelial cell proliferation. Thus recent defensin research has revealed potential links between the innate and acquired immune system.     

Cough sensitivity and extrathoracic airway responsiveness to inhaled capsaicin in chronic cough patients

Enhanced cough response has been frequently observed in chronic cough. Recently, extrathoracic airway constriction to inhaled histamine was demonstrated in some chronic cough patients. However, relation between extrathoracic airway hyperresponsiveness (EAHR) and cough sensitivity determined by capsaicin inhalation is unclear in each etiological entity of chronic cough. Seventy-seven patients, with dry cough persisting for 3 or more weeks, normal spirometry and chest radiography, and 15 controls, underwent methacholine bronchial provocation test and capsaicin cough provocation test. Elicited cough number and flow-volume curve was examined after inhalation of capsaicin to evaluate cough sensitivity and EAHR. Thirty-three patients, with postnasal drip, showed normal extrathoracic airway responsiveness, and 27 of them showed normal cough sensitivity to capsaicin. Cough sensitivity was enhanced in 14 patients with cough variant asthma (CVA) who showed bronchial hyperresponsiveness; EAHR to inhaled capsaicin was present in 12 of them. The remaining 30 patients were tentatively diagnosed as idiopathic chronic cough (ICC). Eleven ICC patients showed enhanced cough sensitivity and EAHR to inhaled capsaicin while 19 patients showed normal values. These results indicate that cough sensitivity is closely related with extrathoracic airway responsiveness during capsaicin provocation in some chronic cough patients. EAHR and enhanced cough sensitivity to inhaled capsaicin may be a part of mechanism developing chronic cough.     

Is there a difference between chronic airway inflammation in chronic severe asthma and chronic obstructive pulmonary disease?

PURPOSE OF REVIEW: The lack of a universally accepted definition of chronic severe asthma and the continuous changes in the classification of the severity of stable chronic obstructive pulmonary disease in the last 10 years make it difficult to compare the many studies available. The aim of the review is to compare studies on chronic severe asthma that have a control group of patients with mild to moderate persistent asthma and studies on stable chronic obstructive pulmonary disease that have an age-matched control group of smokers with normal lung function (with or without chronic bronchitis). RECENT FINDINGS: Our review of the recent literature in this field seems to indicate that chronic airway inflammation in chronic severe asthma is characterized in most cases, both in central and peripheral airways, by the same pathological features of mild-moderate persistent asthma with an increased number of activated T lymphocytes, particularly CD4 Th2 cells, and sometimes eosinophils and mast cells. The most notable difference of chronic severe asthma compared with mild to moderate disease is the increased number of neutrophils. Chronic airway inflammation in stable chronic obstructive pulmonary disease is characterized, both in central and peripheral airways, by an increased number of T lymphocytes, particularly CD8+, macrophages and neutrophils. Macrophage and neutrophil counts increase with the progression of the severity of the disease. SUMMARY: These differences in chronic airway inflammation support the consensus that asthma and chronic obstructive pulmonary disease are different diseases along all their stages of severity.