慢性阻塞性肺疾病的病理生理

慢性阻塞性肺病（chronicobstructlvePJmonarydisease,COPD）指的是具有慢性呼吸道阻塞的支气管炎和肺气肿,不包括还没有慢性气道阻塞的支气管炎和肺气肿,也不包括由其他疾病引起的慢性气道阻塞。然而,由变态反应引起的支气管哮喘的病变实际上也是小支气管的炎症,反复发作     

Pathophysiology of chronic obstructive pulmonary disease

Chronic airflow obstruction (CAO) is a syndrome that is produced by a variety of lesions which may occur in bronchi (large airways), bronchioles (small airways), and lung parenchyma (gas exchanging lung). These lesions frequently occur together in various combinations because of a common etiologic agent, tobacco smoke. Occasionally, one lesion or another may play a dominant role. The major disease of the large airways is chronic bronchitis, or chronic sputum production, and it is defined clinically. Its morphologic counterpart is mucous gland enlargement. Mucous gland enlargement is poorly related to CAO. Other lesions of the large airways--inflammation, smooth muscle hyperplasia, cartilage atrophy, and bronchial wall thickening--have also been described, but their functional consequences are uncertain. Bronchiolar lesions are well recognized in CAO, but their relative importance may differ in patients with mild CAO, compared to patients with severe CAO. In mild CAO, inflammation is a very important lesion, and its probable consequences--narrowing, fibrosis, and goblet cell metaplasia--have all been found to be important. In severe CAO, inflammation and fibrosis do not appear to be important, but goblet cell metaplasia, bronchiolar tortuosity, and narrowing do. Emphysema is a subset of airspace enlargement. Emphysema is defined anatomically and is the most important component of severe CAO. Several forms of emphysema can be recognized morphologically and may have specific clinical associations. However, in the usual patient with severe CAO, it is the severity, rather than the type, of emphysema, that is most significant. The diagnosis of emphysema depends on a combined approach. Significant factors include the clinical history (age, sex, smoking, chronic bronchitis, dyspnea), radiologic evidence of overinflation, and diminished diffusing capacity for carbon monoxide.     

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.     

Partial reversibility of airflow limitation and increased exhaled NO and sputum eosinophilia in chronic obstructive pulmonary disease

We investigated the relationship between the reversibility of airflow limitation, the concentration of nitric oxide (NO) in exhaled air, and the inflammatory cells in the sputum of patients with stable chronic obstructive pulmonary disease (COPD). We examined nine normal healthy control subjects and 20 nonatopic patients with COPD. Ten patients had no reversibility of airflow limitation (increase in FEV(1) of < 12% and < 200 ml after 200 microg of inhaled salbutamol), and 10 patients had partial reversibility of airflow limitation (increase in FEV(1) of < 12% but > 200 ml after 200 microg of inhaled salbutamol). Exhaled NO levels were higher in COPD patients with partial reversibility of airflow limitation than in those with no reversibility of airflow limitation (median 24 [interquartile range 15.3 to 32] ppb versus 8.9 [4.6 to 14.7] ppb; p < 0.01). Compared with healthy control subjects, only COPD patients with partial reversibility of airflow limitation had increased concentrations of sputum eosinophils. We conclude that, in patients with stable COPD, even a partial bronchodilator response to inhaled salbutamol is associated with increased exhaled NO and sputum eosinophilia, suggesting that these patients may have a different response to treatment than do those without reversible airflow limitation.     

Pathophysiology of the small airways in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is characterized by a persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. From a pathological point of view, COPD is characterized by two distinct and frequently coexisting aspects: small airway abnormalities and parenchymal destruction (or emphysema). When pathological changes are localized in lung parenchyma, they will contribute to airflow limitation by reducing the elastic recoil of the lung through parenchymal destruction, as well as by reducing the elastic load applied to the airways through destruction of alveolar attachments. Conversely, when pathological changes involve the small airways, they will contribute to airflow limitation by narrowing and obliterating the lumen and by actively constricting the airways, therefore increasing the resistance. In this article we will review the structural abnormalities in small airways and their relationship with the disordered pulmonary function in COPD, in the attempt to disentangle the mechanisms contributing to the development and progression of airflow limitation in smokers. We will start by describing the normal structure of the small airways, and then observe the main pathological alterations that accumulate in this site and how they parallel pulmonary function derangement.     

Airflow limitation and airway dimensions in chronic obstructive pulmonary disease

RATIONALE: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation caused by emphysema and/or airway narrowing. Computed tomography has been widely used to assess emphysema severity, but less attention has been paid to the assessment of airway disease using computed tomography. OBJECTIVES: To obtain longitudinal images and accurately analyze short axis images of airways with an inner diameter>or=2 mm located anywhere in the lung with new software for measuring airway dimensions using curved multiplanar reconstruction. METHODS: In 52 patients with clinically stable COPD (stage I, 14; stage II, 22; stage III, 14; stage IV, 2), we used the software to analyze the relationship of the airflow limitation index (FEV1, % predicted) with the airway dimensions from the third to the sixth generations of the apical bronchus (B1) of the right upper lobe and the anterior basal bronchus (B8) of the right lower lobe. MEASUREMENTS AND MAIN RESULTS: Airway luminal area (Ai) and wall area percent (WA%) were significantly correlated with FEV1 (% predicted). More importantly, the correlation coefficients (r) improved as the airways became smaller in size from the third (segmental) to sixth generations in both bronchi (Ai: r=0.26, 0.37, 0.58, and 0.64 for B1; r=0.60, 0.65, 0.63, and 0.73 for B8). CONCLUSIONS: We are the first to use three-dimensional computed tomography to demonstrate that airflow limitation in COPD is more closely related to the dimensions of the distal (small) airways than proximal (large) airways.     

An epidemiological study of the effects of statin use on airflow limitation in patients with chronic obstructive pulmonary disease

Background and objective: Chronic obstructive pulmonary disease (COPD) is considered to be a systemic inflammatory disease, and systemic inflammation has been noted as a factor contributing to cardiovascular disease, which is one of the comorbidities associated with COPD. On the other hand, pleiotropic effects, such as the anti‐inflammatory effects of statins, have attracted attention in recent years, and there have been a variety of reports regarding the usefulness of statins for patients with COPD. Methods: We investigated whether the use or non‐use of statins influenced the prevalence of airflow limitation. All outpatients who were over the age of 40 years and who regularly visited a primary health care facility were invited to participate. Each participant underwent spirometry and completed a questionnaire regarding their clinical status, which was used to screen for COPD. A variety of factors that are potentially related to airflow limitation were assessed. Results: Of the 853 patients included in the study, 81 (9.5%) had airflow limitation. The prevalence of airflow limitation was 2.3% among the 89 patients with a history of statin use, which was five times lower than the prevalence of airflow limitation among patients who had not used statins (10.5%). Among the 347 patients with a history of past or current smoking, airflow limitation was not observed in the 30 patients who had used statins. However, by multivariate analysis, statin use was not significantly associated with a lower prevalence of airflow limitation. Conclusions: This is the first cross‐sectional study from Japan that has demonstrated that statin use has a potential impact on airflow limitation in patients with COPD.     

Exercise capacity in chronic obstructive pulmonary disease: mechanisms of limitation

Patients with chronic obstructive pulmonary disease (COPD) are often caught in a downward spiral that progresses from expiratory flow limitation to poor quality of life and invalidity. Within this downward spiral, exercise tolerance represents a key intermediate outcome. As recently stated by the GOLD initiative, improvement in exercise tolerance is now rec ognized as an important goal of COPD treatment. This objective will be achieved only by a comprehensive understanding of the mechanism of exercise limitation in this disease. The objective of this paper is to review the mechanisms of exercise limitation in COPD and discuss their relative contribution to exercise intolerance in patients suffering from this disease.     

A case of severe airflow limitation markedly improved by inhalation therapy in non-smoking woman with chronic obstructive pulmonary disease]

A 67-year old woman who had never smoked presented with dyspnea on effort and general fatigue, which had first appeared 4 years ago. She had lived for 35 years with her husband who was a heavy smoker. Chest roentgenogram showed pulmonary over-inflation, but chest CT scans didn't demonstrate emphysematous changes. Neutrophil-dominant sputum cytology, a PaO2 of 69.5 Torr, and combined ventilatory impairment on respiratory function test were revealed. FEV1.0 improved 80 ml after beta2-agonist inhalation. Although the respiratory symptoms were improved by inhaled anti-cholinergic drug, residual volume increased minimally. After the use of inhaled steroid drug (HFA-BDP) and salmeterol, the symptoms and residual volume were markedly improved. One year later, FEV1.0 increased by 450 ml. The low attenuation area detected by CT scans decreased, mainly in the lower lung field. Passive smoking might have contributed to her airflow limitation.     

Expiratory muscles and exercise limitation in patients with chronic obstructive pulmonary disease

The aim of this study was to estimate, in patients with chronic obstructive pulmonary disease (COPD), the maximal strength of the expiratory muscles, its correlation with exercise performance and the effects of a specific physiotherapy. In 38 COPD men, aged 54 +/- 7 years, pulmonary function data, maximal alveolar pressure (Palv, max) developed during forced vital capacity, were measured using a whole-body plethysmograph and the maximal tolerated power (MTP), i.e. the highest power maintained for at least 3 min, was determined by a progressive test on a treadmill. Airway obstruction was severe (FEV1/FVC: 54 +/- 10%), Palv, max was lower than normal (74 +/- 36 vs. 130 +/- 48 hPa in 20 healthy men of the same age; p less than 0.01) and increased with airway resistance values (Raw); mean MTP was low: 115 +/- 30 W and individual values were inversely related to Raw values. Then, two subgroups of 14 patients were chosen at random. One subgroup received an abdominal muscle physiotherapy during 3 weeks. The other subgroup only received usual medical treatment. No modification in any parameter was found in the second subgroup. Specific physiotherapy of abdominal muscles improves significantly both Palv, max (118 +/- 45 hPa) and MTP (171 +/- 38 W; p less than 0.01), without any variation in other respiratory function parameters. We conclude that abdominal muscle weakness is common in COPD patients and can participate in the limitation in exercise performance. Specific physiotherapy increases abdominal muscle strength and seems to improve exercise tolerance by a still unexplained mechanism.     

Right ventricular dysfunction and the exercise limitation of chronic obstructive pulmonary disease

This study examined right ventricular function during exercise in patients with chronic obstructive pulmonary disease to answer the following questions: Is there a significant correlation between oxygen consumption at maximal exercise and exercise right ventricular ejection fraction? Does the right ventricular ejection fraction response to exercise correlate with exercise changes in pulmonary artery pressure, total pulmonary resistance or pulmonary vascular resistance? Which combinations of cardiac, ventilatory and blood gas variables are the best predictors of oxygen consumption at maximal exercise? Twenty-six patients with stable chronic obstructive pulmonary disease performed symptom-limited supine bicycle exercise with simultaneous hemodynamic and radionuclide ventriculographic measurements. The oxygen consumption at maximal exercise correlated with the exercise right ventricular ejection fraction (n = 21, r = 0.66; p less than 0.005), exercise stroke volume (r = 0.68; p less than 0.001), exercise cardiac output (r = 0.77; p less than 0.00005) and exercise ventilation (r = 0.85; p less than 0.00001). The change in right ventricular ejection fraction from rest to exercise correlated inversely with the change from rest to exercise in total pulmonary resistance (r = -0.51; p less than 0.05) but not with the change in mean pulmonary pressure (r = -0.37) or in pulmonary vascular resistance (r = 0.09). Multivariate analysis showed that the variables giving the highest combined correlation with oxygen consumption were ventilation and right ventricular ejection fraction (r = 0.95, adjusted r2 = 0.88). These results suggest that exercise oxygen consumption of patients with chronic obstructive pulmonary disease is related to right ventricular systolic function, exercise right ventricular dysfunction is related, in part, to abnormal exercise total pulmonary resistance, and exercise limitation in chronic obstructive pulmonary disease occurs as a result of the dynamic interaction between disordered right heart function and ventilation.     

Effects of hyperoxia on ventilatory limitation during exercise in advanced chronic obstructive pulmonary disease

We studied interrelationships between exercise endurance, ventilatory demand, operational lung volumes, and dyspnea during acute hyperoxia in ventilatory-limited patients with advanced chronic obstructive pulmonary disease (COPD). Eleven patients with COPD (FEV(1.0) = 31 +/- 3% predicted, mean +/- SEM) and chronic respiratory failure (Pa(O(2)) 52 +/- 2 mm Hg, Pa(CO(2 ))48 +/- 2 mm Hg) breathed room air (RA) or 60% O(2) during two cycle exercise tests at 50% of their maximal exercise capacity, in randomized order. Endurance time (T(lim)), dyspnea intensity (Borg Scale), ventilation (V E), breathing pattern, dynamic inspiratory capacity (IC(dyn)), and gas exchange were compared. Pa(O(2)) at end-exercise was 46 +/- 3 and 245 +/- 10 mm Hg during RA and O(2), respectively. During O(2), T(lim) increased 4.7 +/- 1.4 min (p < 0.001); slopes of Borg, V E, V CO(2), and lactate over time fell (p < 0.05); slopes of Borg-V E, V E-V CO(2), V E-lactate were unchanged. At a standardized time near end-exercise, O(2) reduced dyspnea 2.0 +/- 0.5 Borg units, V CO(2) 0.06 +/- 0.03 L/min, V E 2.8 +/- 1.0 L/min, and breathing frequency 4.4 +/- 1.1 breaths/min (p < 0.05 each). IC(dyn) and inspiratory reserve volume (IRV) increased throughout exercise with O(2) (p < 0.05). Increased IC(dyn) was explained by the combination of increased resting IRV and decreased exercise breathing frequency (r(2) = 0.83, p < 0.0005). In conclusion, improved exercise endurance during hyperoxia was explained, in part, by a combination of reduced ventilatory demand, improved operational lung volumes, and dyspnea alleviation.     

Association between airflow limitation and prognosis in patients with chronic pulmonary aspergillosis

BackgroundPrevious studies have shown that reduced levels of lung function, characterized by forced expiratory volume in 1 second (FEV₁), are associated with higher respiratory events and mortality in general population and some chronic lung diseases. Chronic pulmonary aspergillosis (CPA) is a destructive, fatal lung disease caused by Aspergillus infection in non-immunocompromised patients with suboptimal pulmonary function. However, there is limited information on the status and features of CPA according to FEV₁.MethodsWe performed a retrospective observational study to investigate the FEV₁ and airflow limitation in patients with CPA between March 2017 and February 2019 at a tertiary hospital in South Korea.ResultsOf the 144 CPA patients, 104 underwent spirometry, demonstrating median forced vital capacity (FVC) and FEV₁ of 2.35 L (68%) and 1.43 L (62%), respectively. Among them, 56 patients had airflow limitation on PFT, with median FVC, and FEV₁ of 2.47 L (73%) and 1.11 L (47%), respectively. Low body mass index (BMI) (20.1 vs. 22.1 kg/m²; P=0.011), breathlessness (60% vs. 20%; P=0.002), and bilateral pulmonary lesions (33.3% vs. 4%; P=0.006) were more common in patients with moderate to very severe airflow limitation than in those with normal to mild airflow limitation.ConclusionsModerate to very severe airflow limitation was observed in 43.3% of patients with CPA. Additionally, low BMI, breathlessness, and bilateral pulmonary lesions contributing to poor prognosis were more common in patients with moderate to very severe airflow limitation than in those with normal to mild airflow limitation. Our findings suggest that airflow limitation can be associated with the prognosis of CPA. Further investigations are needed to demonstrate the clinical significance of this association.     

体表潮气呼吸模式评价中重度慢性阻塞性肺疾病患者的气流限制

目的探讨用呼吸电感体积描记法（RIP）监测潮气呼吸时的体表呼吸模式能否评价阻塞性肺疾病（COPD）的气流限制.方法重度COPD患者13例、中度COPD患者10例和11名健康者（对照组）均接受肺通气功能和RIP检查.结果与对照组比较中度患者体表呼吸模式无差异;而重度患者的Ti、Ti/Ttot、TPTEF/TETE指标差异有显著性.TPTEF/TE和FEV1.0/FVC、FEV1.0%均具有独立的线性相关.结论体表监测潮气呼吸模式如TPTEF/TE可评价重度COPD患者的气流限制.     

吸入沙丁胺醇对慢性阻塞性肺疾病患者呼气流速受限的影响

目的　评价吸入支气管扩张剂治疗对慢性阻塞性肺疾病 (COPD)患者呼气流速受限 (EFL)的影响。方法　 2 8例稳定期中、重度COPD患者在吸入沙丁胺醇干粉剂前后行常规肺功能测定和呼气负压 (NEP)测试。结果　NEP测试显示所有患者均存在EFL。吸入沙丁胺醇后FEV1 ,FVC和FEF50 iso vol均有显著增高 ,流速受限 (FL)指数则明显下降〔(79.1± 1 2 .0 ) %与 (63 .2± 1 2 .9) % ,P <0 .0 1〕。 1 1例COPD患者的FEV1 ≥ 1 5 % (阳性组 ) ,其余1 7例FEV1 <1 5 % (阴性组 ) ,两组患者的FEF50 iso vol和FL指数则无明显差异 (FEF50 iso vol为 (43 .3± 2 0 .2 ) %与 (39.6± 2 1 .7) % ,FL指数为〔(2 1 .5± 8.4) %与 (1 9.6± 1 1 .7) % ,均P >0 .0 5〕。FL指数与ΔFEF50 % iso vol呈显著相关(r =0 .50 8,P <0 .0 1 ) ,而与FEV1 的相关性不明显 (r=0 .1 0 6 ,P >0 .0 5)。结论　COPD患者在吸入支气管扩张剂后其EFL可得到显著改善 ,FVC和FEV1 均显著增加 ,EFL的改善程度相当于FEF50 %的改变程度