Asthma as a risk factor for COPD in a longitudinal study

BACKGROUND: For several years, asthma and COPD have been regarded as distinct entities, with distinct clinical courses. However, despite distinctive physiologic features at the time of diagnosis, and different risk factors, the two diseases over time may develop features that are quite similar. STUDY OBJECTIVE: To evaluate the association between physician-diagnosed asthma and the subsequent development of COPD in a cohort of 3,099 adult subjects from Tucson, AZ. DESIGN AND METHODS: A prospective observational study. Participants completed up to 12 standard respiratory questionnaires and 11 spirometry lung function measurements over a period of 20 years. Survival curves (with time to development of COPD as the dependent variable) were compared between subjects with asthma and subjects without asthma at the initial survey. RESULTS: Subjects with active asthma (n = 192) had significantly higher hazard ratios than inactive (n = 156) or nonasthmatic subjects (n = 2751) for acquiring COPD. As compared with nonasthmatics, active asthmatics had a 10-times-higher risk for acquiring symptoms of chronic bronchitis (95% confidence interval [CI], 4.94 to 20.25), 17-times-higher risk of receiving a diagnosis of emphysema (95% CI, 8.31 to 34.83), and 12.5-times-higher risk of fulfilling COPD criteria (95% CI, 6.84 to 22.84), even after adjusting for smoking history and other potential confounders. CONCLUSIONS: Physician-diagnosed asthma is significantly associated with an increased risk for CB, emphysema, and COPD.     

Clinical phenotypes of obstructive airway diseases in an outpatient population

Background and Objectives: Historically, obstructive airway diseases such as asthma and COPD are classified as different diseases. Although the definitions are clearly described, classification of patients into these traditional, clinical disease entity can be difficult. Recent evidence that there are complex, overlapping phenotypes of obstructive lung disease. Our aim was to capture clinical phenotypes of obstructive diseases through the use of cluster analysis in a representative patient population at a common Dutch pulmonary outpatient clinic. Clinical physiological and cellular/ molecular markers were used in the analysis. Methods: To carry out the cluster analysis, an imputed dataset was created from a random sample of 191 adult patients chosen from a pulmonary outpatient clinic. The selection criteria from the sample included patients with a doctor's diagnosis for asthma or COPD. Detailed assessment of patient pulmonary function, blood eosinophil counts, allergic sensitisation and smoking history was collected. Results: We observed four distinct clusters with different clinical characteristics of obstructive lung diseases. Cluster 1: patients with a history of extensive cigarette smoking, airway obstruction without signs of emphysema; cluster 2: patients with features of the emphysematous type of COPD; cluster 3: patients with characteristics of allergic asthma; cluster 4: patients with features suggesting an overlap syndrome of atopic asthma and COPD. Conclusion: Four phenotypes of obstructive lung disease were identified amongst patients clinically labelled as asthma or COPD. These findings emphasize the concept that there are different phenotypes of obstructive lung diseases, including overlapping and complementary disease entities. These phenotypes of chronic airways disease can serve to tailor disease management.     

A 24-year old man with persistent progressive breathlessness: early onset COPD.

We describe the case of a 24-year old male who had been a heavy smoker since the age of 9 and who presented with an 8-year history of respiratory symptoms. He was having treatment for asthma. Spirometric studies and high-resolution computed tomography (HRCT) scans confirmed COPD with centrilobular emphysema. His blood level of alpha-1-antitrypsin was within the normal range. Early onset emphysema in smokers with a normal alpha-1-antitrypsin has been previously described. However, this case is, as far as we know, one of the youngest cases ever reported.     

Influence of C-159T SNP of the CD14 gene promoter on lung function in smokers

CD14, a co-receptor for endotoxin, plays a significant role in regulating the inflammatory response to this agent. The C-159T single nucleotide polymorphism (SNP) in the CD14 gene promoter is an important regulator of CD14 expression, with TT homozygotes having increased expression of CD14. This SNP has been linked to pathogenesis of asthma and with cardiovascular diseases in smokers. We hypothesize that CD14 also plays a role in the pathophysiology of COPD in smokers who are exposed to endotoxin contained in cigarette smoke as well as endotoxin derived from Gram-negative microbes colonizing their airways. To assess the effect of the C-159T SNP of the CD14 gene promoter on lung function, we recruited 246 smokers 40 years of age or older with a range of 10–156 pack-year smoking exposures. The TT genotype was associated with lower lung function in smokers with a moderate smoking history. However, the CC genotype was associated with decreased lung function in heavy smokers (>56 pack years). The effect of CC genotype on severity of COPD is analogous with the effect of this genotype in risk for asthma. CD14 may be a factor in the pathophysiology of COPD, as it is in asthma and smoking-related cardiovascular diseases.     

Alphabet Soup: Assessment of Dyspnea

Abstract

The purposes of this study were: to describe chest CT findings in normal non-smoking controls and cigarette smokers with and without COPD; to compare the prevalence of CT abnormalities with severity of COPD; and to evaluate concordance between visual and quantitative chest CT (QCT) scoring. Methods: Volumetric inspiratory and expiratory CT scans of 294 subjects, including normal non-smokers, smokers without COPD, and smokers with GOLD Stage I-IV COPD, were scored at a multi-reader workshop using a standardized worksheet. There were 58 observers (33 pulmonologists, 25 radiologists); each scan was scored by 9–11 observers. Interobserver agreement was calculated using kappa statistic. Median score of visual observations was compared with QCT measurements. Results: Interobserver agreement was moderate for the presence or absence of emphysema and for the presence of panlobular emphysema; fair for the presence of centrilobular, paraseptal, and bullous emphysema subtypes and for the presence of bronchial wall thickening; and poor for gas trapping, centrilobular nodularity, mosaic attenuation, and bronchial dilation. Agreement was similar for radiologists and pulmonologists. The prevalence on CT readings of most abnormalities (e.g. emphysema, bronchial wall thickening, mosaic attenuation, expiratory gas trapping) increased significantly with greater COPD severity, while the prevalence of centrilobular nodularity decreased. Concordances between visual scoring and quantitative scoring of emphysema, gas trapping and airway wall thickening were 75%, 87% and 65%, respectively. Conclusions: Despite substantial inter-observer variation, visual assessment of chest CT scans in cigarette smokers provides information regarding lung disease severity; visual scoring may be complementary to quantitative evaluation.     

Comparison of lung morphology in COPD secondary to cigarette and biomass smoke

OBJECTIVE: To compare lung morphology in chronic obstructive pulmonary disease (COPD) secondary to cigarette smoke (CS) and biomass smoke (BS). METHODS: Necropsies of women with COPD diagnosis by lung pathology and unique exposure to BS (n = 27) or CS (n = 21) matched by age and place of origin. Lungs were macroscopically and microscopically examined to evaluate the extent of emphysema, pigment deposition, and abnormalities in pulmonary arteries, large airways (including the Reid index) and small airways (SAWs) by a semiquantitative method. RESULTS: Both groups had variable degrees of emphysema and SAWs disease. Patients exposed to BS had more lung fibrosis and pigment deposition and thicker pulmonary arterial intima than smokers, who had more emphysema and epithelial damage (goblet cell metaplasia). The Reid index was similar in both groups. CONCLUSION: Lengthy exposure to BS can produce emphysema and other lesions typically observed in cigarette smokers, but with a slightly different distribution. Whether the differences observed are the consequence of severity of exposure or smoke composition, or both, remains to be clarified.     

Exposing a deadly alliance: Novel insights into the biological links between COPD and lung cancer

Chronic obstructive pulmonary disease (COPD) affects more than 200 million people worldwide and is expected to become the third leading cause of death in 2020. COPD is characterized by progressive airflow limitation, due to a combination of chronic inflammation and remodeling of the small airways (bronchiolitis) and loss of elastic recoil caused by destruction of the alveolar walls (emphysema). Lung cancer is the most important cause of cancer-related death in the world. (Cigarette) smoking is the principal culprit causing both COPD and lung cancer; in addition, exposure to environmental tobacco smoke, biomass fuel smoke, coal smoke and outdoor air pollution have also been associated with an increased incidence of both diseases. Importantly, smokers with COPD – defined as either not fully reversible airflow limitation or emphysema – have a two- to four-fold increased risk to develop lung cancer. In this review, we highlight several of the genetic, epigenetic and inflammatory mechanisms, which link COPD and carcinogenesis in the lungs. Elucidating the biological pathways and networks, which underlie the increased susceptibility of lung cancer in patients with COPD, has important implications for screening, prevention, diagnosis and treatment of these two devastating pulmonary diseases.     

Wie funktioniert die Lunge im Alter?

Advanced age is associated with significant changes in lung structure, a decline in lung function, changes in the immune system and impairment of the physical barriers that protect against invading particles and organisms. These alterations in respiratory physiology and immune function coupled with low grade chronic inflammation of lung tissue induced by environmental exposure or endogenous factors may, at least in part, account for the increase in susceptibility to characteristic illnesses. These include chronic bronchitis, emphysema, chronic obstructive pulmonary disease (COPD), neoplasia and infections including pneumonia as a leading cause of illness and death in the elderly.     

维生素D在肺部疾病中的作用

除了维持钙盐代谢和骨骼的稳态以外，研究发现维生素D还可调控包括机体防御，炎症，免疫，损伤修复等在内的多种生理和病理生理过程。流行病学资料表明，血清低水平的维生素D与肺功能受损、炎症反应和感染性疾病相关。因此，支气管哮喘、慢性阻塞性肺疾病和肺部感染性疾病都可能与维生素D水平有关，但具体的机制尚不明确。因此，本文通过文献回顾，概述维生素D在肺部疾病，包括支气管哮喘、慢性阻塞性肺疾病、肺结核和呼吸道感染中的作用。     

CT emphysema predicts thoracic aortic calcification in smokers with and without COPD

COPD patients are at increased risk for cardiovascular morbidity and mortality independent of smoking habits. Recent studies suggest CT emphysema is an independent predictor of cardiovascular risk as evidenced by its association with arterial stiffness and impaired endothelial function. We examined the relationship between demographics, lung function, CT emphysema and airway wall thickness and thoracic aortic calcification, another marker of cardiovascular risk, in the National Lung Screening Trial. We hypothesized that CT emphysema would be independently associated with thoracic aortic calcification. Two hundred forty current and former smokers were enrolled. After CT examination, we recorded subjects' demographics and they performed spirometry. Subjects were classified into COPD and non-COPD subgroups. CT emphysema was quantified as a percentage of lung volume and measurements of the right upper lobe airway were performed using standard methods and expressed as wall area (%). Total calcification scores for the thoracic aorta were computed using TeraRecon image analysis. Univariate and multivariate analyses were performed to determine the associations between calcium score and subject characteristics. Subjects with COPD were older, more often male, heavier smokers and had more CT emphysema and greater aortic calcification than those without COPD. Calcium score was associated with age, pack-years, CT emphysema, wall area%, and lung function on univariate testing but only with age and CT emphysema on multivariate analysis. We conclude that CT emphysema is independently associated with thoracic calcification and thus may be used to assess cardiovascular risk in smokers with and without COPD.     

Pathogenesis of COPD

Chronic obstructive pulmonary disease (COPD) is characterized and defined by limitation of expiratory airflow. This can result from several types of anatomical lesions, including loss of lung elastic recoil and fibrosis and narrowing of small airways. Inflammation, edema, and secretions also contribute variably to airflow limitation. Smoking can cause COPD through several mechanisms. First, smoke is a powerful inducer of an inflammatory response. Inflammatory mediators, including oxidants and proteases, are believed to play a major role in causing lung damage. Smoke can also alter lung repair responses in several ways. Inhibition of repair may lead to tissue destruction that characterizes emphysema, whereas abnormal repair can lead to the peribronchiolar fibrosis that causes airflow limitation in small airways. Genetic factors likely play a major role and probably account for much of the heterogeneity susceptibility to smoke and other factors. Many factors may play a role, but to date, only alpha-1 protease inhibitor deficiency has been unambiguously identified. Exposures other than cigarette smoke can contribute to the development of COPD. Inflammation of the lower respiratory tract that results from asthma or other chronic disorders may also contribute to the development of fixed airway obstruction. COPD is not only a disease of the lungs but is also a systemic inflammatory disorder. Muscular weakness, increased risk for atherosclerotic vascular disease, depression, osteoporosis, and abnormalities in fluids and electrolyte balance may all be consequences of COPD. Advances in understanding the pathogenesis of COPD have the potential for identifying new therapeutic targets that could alter the natural history of this devastating disorder.     

Airway dimensions and pulmonary function in chronic obstructive pulmonary disease and bronchial asthma

Background and objective: COPD and bronchial asthma are chronic airway diseases with a different pathogenesis. Comparisons of differences in airway calibre by bronchial generation between these diseases and their importance to pulmonary function have not been fully studied. We investigated airway calibre and wall thickness in relation to pulmonary function in patients with asthma, COPD, asthma plus emphysema and normal subjects using CT. Methods: Sixty‐three asthmatic patients, 46 COPD, 23 patients with asthma plus emphysema and 61 control subjects were studied cross‐sectionally. We used a software with curved multiplanar reconstruction to measure airway dimensions from 3rd‐ to 6th‐generation bronchi of the right lower posterior bronchus. Results: Patients with COPD had increased wall thickness, but the airway was not narrow from the 3rd‐(subsegmental) to 6th‐generation bronchi. Mean bronchial inner diameter (Di) of 3rd‐ to 6th‐generation bronchi in patients with asthma or asthma plus emphysema was smaller than that of COPD patients and normal subjects. Airway luminal area (Ai) of 5th‐generation bronchi most closely correlated with pulmonary function in patients with stable asthma. Although Di was similar in patients with asthma and asthma plus emphysema, the Ai of 6th‐generation bronchi correlated significantly with pulmonary function in patients with asthma plus emphysema. Conclusions: Airway calibre in asthma may be smaller than in COPD. Airflow limitations correlated more closely with peripheral Ai in patients with asthma plus emphysema than in patients with asthma alone.     

CT Emphysema Predicts Thoracic Aortic Calcification in Smokers with and Without COPD

ABSTRACT

COPD patients are at increased risk for cardiovascular morbidity and mortality independent of smoking habits. Recent studies suggest CT emphysema is an independent predictor of cardiovascular risk as evidenced by its association with arterial stiffness and impaired endothelial function. We examined the relationship between demographics, lung function, CT emphysema and airway wall thickness and thoracic aortic calcification, another marker of cardiovascular risk, in the National Lung Screening Trial. We hypothesized that CT emphysema would be independently associated with thoracic aortic calcification. Two hundred forty current and former smokers were enrolled. After CT examination, we recorded subjects’ demographics and they performed spirometry. Subjects were classified into COPD and non-COPD subgroups. CT emphysema was quantified as a percentage of lung volume and measurements of the right upper lobe airway were performed using standard methods and expressed as wall area (%). Total calcification scores for the thoracic aorta were computed using TeraRecon image analysis. Univariate and multivariate analyses were performed to determine the associations between calcium score and subject characteristics. Subjects with COPD were older, more often male, heavier smokers and had more CT emphysema and greater aortic calcification than those without COPD. Calcium score was associated with age, pack-years, CT emphysema, wall area%, and lung function on univariate testing but only with age and CT emphysema on multivariate analysis. We conclude that CT emphysema is independently associated with thoracic calcification and thus may be used to assess cardiovascular risk in smokers with and without COPD.     

Diagnostics différentiels de l’asthme

The differential diagnosis of asthma has to be considered in two situations: first, during the first encounter with the patient (lung function tests with pharmacological testing are crucial in this context) and during follow-up visits, if symptoms are not controlled in spite of adequate treatment. At the time of the initial diagnosis, the patient’s age and the clinical presentation will guide investigations. In middle-aged smokers, it may be difficult to differentiate asthma and COPD, since both diseases may be present. During follow-up, other diseases, such as gastro-oesophageal reflux, vasculitis, allergic bronchopulmonary aspergillosis, left heart failure, etc., may be associated with the asthma, increasing respiratory symptoms. Finally, remember that vocal cord dysfunction can mimic asthma.     

COPD与肺癌发病的相关性

目的：研究COPD与肺癌发病的相关性。方法收集2010年11月至2013年11月我院收治的门诊或住院患者210例肺癌患者作为实验组,同时选取在玉林市红十字会医院体检中心体检的非癌健康人226例作为对照组,观察2组研究对象个人呼吸系统疾病史、家族呼吸系统疾病史与肺癌之间的关系,同时观察2组中吸烟患者和不吸烟患者的 COPD 发生率。结果呼吸系统疾病中肺炎、哮喘与肺癌的发生无显著关系(P 值均>0.05)；伴有 COPD、支气管炎、肺气肿、肺结核的患者,发生肺癌的风险显著增高(P 值均<0.05),其中 COPD 与肺癌发生的关联性最强(OR =2.73)。具有COPD及肺癌家族史的人群,发生肺癌的风险显著增加(P<0.05)。吸烟患者中实验组COPD的发生率显著高于对照组(χ2=5.482,P<0.05)；实验组未吸烟患者中实验组 COPD的发生率显著高于对照组(χ2=5.901,P<0.05)。结论患有COPD病史及有 COPD家族史的患者,发生肺癌的风险增加,且COPD患者无论是否吸烟,COPD仍然会导致肺癌发生的风险性增加。     

Elastase/antielastase systems in pulmonary diseases

Levels of serum elastase 1 in a variety of respiratory diseases were studied. In patients with pulmonary emphysema, pulmonary fibrosis, bronchial asthma, or pulmonary infections, including pneumonia and pulmonary tuberculosis, serum elastase 1 levels were greater than those of an age-matched control group. In lung cancer patients, however, the serum elastase 1 level was within normal limits. Although alpha 1-antitrypsin levels were significantly higher in patients with pulmonary infections and lung cancer than in the normal group, they were within normal limits in patients with pulmonary emphysema, pulmonary fibrosis, and bronchial asthma. Alpha 2-macroglobulin levels were slightly increased in patients with pulmonary emphysema and pneumonia. These results suggest that the increases in serum elastase 1 levels in these respiratory diseases may be mainly caused by an imbalance of elastase/antielastase system in the lung tissue and the bloodstream.     

Genetic Backgrounds of Asthma and COPD

Asthma and COPD are complex diseases with strong genetic and environmental components. These common pulmonary diseases have both different and similar clinical features. Molecular genetic techniques are being used to improve understanding of these common late onset disorders. Recently, several genes and genetic loci associated with increased susceptibility to asthma and COPD have been described. Many of these genes are expressed in the lung tissues, indicating that events in lung tissues might drive disease processes. Lung tissues are rich sources of innate danger signals, and an increased understanding of how the lung tissues communicate with the immune system to maintain healthy tissue might provide new insights into the pathogenesis of chronic inflammatory lung diseases in which injury and repair are in disequilibrium. Given that the innate immune system is at the interface between the airways and environmental insults, genetic polymorphisms in genes related to the innate immune system are likely to affect susceptibility to both asthma and CopD. In addition, some findings from genetic studies provide molecular support for the point of view proposed in the Dutch hypothesis regarding the relationship between asthma and COPD, which highlights the complexity of the pathways that can induce small airway disease and suggests that there is a continuum between asthma and COPD.     

Pulmonary surfactant in health and human lung diseases: state of the art.

Pulmonary surfactant is a complex and highly surface active material composed of lipids and proteins which is found in the fluid lining the alveolar surface of the lungs. Surfactant prevents alveolar collapse at low lung volume, and preserves bronchiolar patency during normal and forced respiration (biophysical functions). In addition, it is involved in the protection of the lungs from injuries and infections caused by inhaled particles and micro-organisms (immunological, non-biophysical functions). Pulmonary surfactant can only be harvested by lavage procedures, which may disrupt its pre-existing biophysical and biochemical micro-organization. These limitations must always be considered when interpreting ex vivo studies of pulmonary surfactant. A pathophysiological role for surfactant was first appreciated in premature infants with respiratory distress syndrome and hyaline membrane disease, a condition which is nowadays routinely treated with exogenous surfactant replacement. Biochemical surfactant abnormalities of varying degrees have been described in obstructive lung diseases (asthma, bronchiolitis, chronic obstructive pulmonary disease, and following lung transplantation), infectious and suppurative lung diseases (cystic fibrosis, pneumonia, and human immunodeficiency virus), adult respiratory distress syndrome, pulmonary oedema, other diseases specific to infants (chronic lung disease of prematurity, and surfactant protein-B deficiency), interstitial lung diseases (sarcoidosis, idiopathic pulmonary fibrosis, and hypersensitivity pneumonitis), pulmonary alveolar proteinosis, following cardiopulmonary bypass, and in smokers. For some pulmonary conditions surfactant replacement therapy is on the horizon, but for the majority much more needs to be learnt about the pathophysiological role the observed surfactant abnormalities may have.     

Identification of Occult Parechymal Disease Such as Emphysema or Airway Disease Using Screening Computed Tomography

ABSTRACT

Rationale: Chronic obstructive pulmonary disease (COPD) is a major public health problem. This study was performed to determine whether the low attenuation area (LAA) and visual score provided by low-dose computed tomography (CT) can be used to detect occult parenchymal disease, such as insidious COPD. Methods: Each participant underwent low-dose CT scan and pulmonary function tests. The LAA% of the corresponding lung area was calculated. The cut-off level between the normal lung density area and LAA was defined as –960 HU, and the severity of emphysematous change (visual score) and LAA% were evaluated on three same chest CT slices obtained at full inspiration. Results: Forty-eight of 2,247 individuals including 1058 non-smokers and 1189 smokers were diagnosed with COPD. Chest CT findings in individuals diagnosed with COPD showed centrilobular emphysema (50%), however, 17 of the subjects diagnosed with COPD had normal screening CT findings. Thirty-one subjects diagnosed with COPD showed a positive visual score, and 27 individuals with COPD showed LAA% of more than 30. Nine of 17 subjects with a negative visual score showed LAA% of more than 30. The visual score in smokers was significantly higher than that of non-smokers. The lung function in smokers was lower than that of non-smokers. Smokers also showed higher frequencies of chest CT abnormalities. Conclusion: Low-dose CT scans detected LAA and a positive visual score before COPD associated with an impaired lung function develops. Smokers with normal spirometry had a potential to develop an airflow obstruction accompanied with abnormal CT findings.