Clinical characteristics of combined pulmonary fibrosis and emphysema

Background and objective: Patients with combined pulmonary fibrosis and emphysema (CPFE) are sometimes seen, and we speculate that these patients have some different clinical characteristics from COPD patients. This study clarifies the clinical characteristics of CPFE patients. Methods: This was a retrospective study of 47 stable patients with concurrent emphysema and diffuse parenchymal lung disease with fibrosis, based on the findings of chest CT (CPFE patients). The clinical characteristics of CPFE patients were compared with those of emphysema‐dominant COPD patients without parenchymal lung disease (COPD patients). Results: Forty‐six of the 47 CPFE patients were male. Paraseptal emphysema was particularly common in the CPFE group. Honeycombing, ground‐glass opacities and reticular opacities were present in 75.6%, 62.2% and 84.4% of CPFE patients, respectively. Twenty‐two of the 47 CPFE patients (46.8%) had lung cancer. Pulmonary function tests showed that the CPFE group had milder airflow limitation and lower diffusing capacity than the COPD group. Desaturation during 6‐min walking test in CPFE patients tended to be more severe than in COPD patients, if the level of FEV₁ or 6MWD was equal. Conclusions: CPFE patients had some different clinical characteristics in comparison with COPD patients and may also have a high prevalence of lung cancer.     

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.     

Assessment of emphysema in COPD: a functional and radiologic study

OBJECTIVES: A combination of functional measurements reflecting a decrease in maximum flow, a degree of lung hyperinflation, the relationship between maximum inspiratory and expiratory flows, bronchodilator response, and diffusing capacity of the lung for carbon monoxide (DLCO) was used to quantify the extent of emphysema, as assessed by high-resolution CT (HRCT) scanning. DESIGN: Forced inspiratory and expiratory spirometry, lung volumes, reversibility test, and single-breath diffusing capacity were assessed before and after inhaling albuterol, 200 microg. Relationships between lung function variables and emphysema extent, as determined by HRCT scanning, were tested by univariate and multivariate analyses. SUBJECTS: Thirty-nine COPD outpatients with moderate-to-severe obstruction. MEASUREMENTS AND RESULTS: Emphysema extent, as assessed by HRCT scanning, ranged from 18 to 70%. All of the lung function parameters that were studied, except for the change in FEV1 percent predicted after salbutamol inhalation, correlated significantly with the extent of emphysema (r2 range, 0.19 to 0.44). Functional residual capacity, forced expiratory flow at 50% of FVC/forced inspiratory flow at 50% of FVC, DLCO/alveolar volume ratio, and bronchodilator-induced change in FEV1/FVC ratio were the only variables retained by stepwise multiple regression analysis. The multiple regression model explained 71% of the variability of emphysema extent measured by HRCT scanning. CONCLUSIONS: The combination of lung function measurements reflecting lung hyperinflation, bronchial collapsibility, lung diffusing capacity, and bronchodilator response provides a good estimate of the extent of emphysema, as evaluated by HRCT scanning. These data suggest that pulmonary function tests are useful in assessing and monitoring parenchymal damage in COPD patients.     

Low awareness of COPD among physicians

Introduction: Early identification of patients with chronic obstructive pulmonary disease (COPD) in the health care system followed by successful smoking cessation may prevent rapid lung function deterioration, development of severe COPD and respiratory failure. Objectives: The aim of this study was to determine the frequency of under‐diagnosed chronic obstructive lung diseases among current smokers. Materials and methods: The under‐diagnosis of COPD among smokers was determined in subjects who participated in a screening procedure aimed at recruiting COPD patients for a smoking cessation programme. In order to identify current smokers, a questionnaire was sent out to persons who had been on sick leave for various reasons certified by a physician for more than 2 weeks. Subjects who stated that they currently smoked more than eight cigarettes per day were invited to perform a lung function test. Results: A total of 3887 subjects performed spirometry, i.e. forced expiratory volume in 1 s and forced expirations, and among these, 674 (17.3%) had COPD according to the European Respiratory Society (ERS) consensus guidelines. Of those, 103 (17.3%) had physician‐diagnosed COPD. Productive cough was reported by 16.6% of the COPD subjects. Despite the fact that smokers were on sick leave certified by a physician, more than 80% of those with COPD had no previous diagnosis. As the COPD diagnosis cannot be based on reported symptoms, a spirometry on persons at risk must be performed. Conclusion: The awareness of COPD among primary care physicians has to increase and smokers above the age of 40, with and without respiratory symptoms, have to undergo spirometry if it is regarded important to establish the COPD diagnosis at an early stage. Please cite this paper as: Sundblad B‐M, Larsson K and Nathell L. Low awareness of COPD among physicians. The Clinical Respiratory Journal 2008; 2: 11–16.     

This is what COPD looks like

Despite decades of research, and the growing healthcare and societal burden of chronic obstructive pulmonary disease (COPD), therapeutic COPD breakthroughs have not occurred. Sub‐optimal COPD patient phenotyping, an incomplete understanding of COPD pathogenesis and a scarcity of sensitive tools that provide patient‐relevant intermediate endpoints likely all play a role in the lack of new, efficacious COPD interventions. In other words, COPD patients are still diagnosed based on the presence of persistent airflow limitation measured using spirometry. Spirometry measurements reflect the global sum of all the different possible COPD pathologies and perhaps because of this, we lose sight of the different contributions of airway and parenchymal abnormalities. With recent advances in thoracic X‐ray computed tomography (CT) and magnetic resonance imaging (MRI), lung structure and function abnormalities may be regionally identified and measured. These imaging endpoints may serve as biomarkers of COPD that can be used to better phenotype patients. Therefore, here we review novel CT and MRI measurements that help reveal COPD phenotypes and what COPD really ‘looks’ like, beyond spirometric indices. We discuss MR and CT imaging approaches for generating reproducible and sensitive measurements of COPD phenotypes related to pulmonary ventilation and perfusion as well as airway and parenchyma anatomical and morphological features. These measurements may provide a way to advance the development and testing of new COPD interventions and therapies.     

High resolution CT and bronchial reversibility test for diagnosing COPD

BACKGROUND: COPD is defined by airflow limitation that is not fully reversible and is associated with relevant risk factors. The diagnosis requires that other causes of chronic airflow limitation (CAL) be excluded. We assessed the diagnostic utility of high resolution thoracic CT (HRCT) and bronchodilator reversibility to assist in making a diagnosis of COPD. METHODOLOGY: We investigated 516 consecutive patients whose FEV1/FVC was less than 70% after inhalation of bronchodilator. HRCT was performed on all subjects and a final diagnosis was made only after 3 months of treatment and repeated spirometry. RESULTS: Of 516 cases, 54.3% had COPD, 19.8% had asthma plus emphysema, and 13.2% had chronic asthma. The remaining 12.7% of patients with CAL had diffuse panbronchiolitis, bronchiectasis, bronchiolitis obliterans, or other miscellaneous diseases. In these minor diseases HRCT was essential in making a definitive diagnosis. The sensitivities of emphysema on HRCT and of absence of bronchodilator response for the diagnosis of COPD were 81% and 90%, respectively, and the specificities of the tests were 57% and 37%, respectively. In addition, HRCT revealed considerable heterogeneity of COPD. Emphysema was not recognized on HRCT in 18.6% of COPD patients. HRCT also revealed that 17.5% of COPD patients had other pulmonary complications including lung fibrosis compatible with usual interstitial pneumonia in the lung bases. CONCLUSIONS: HRCT and the bronchial reversibility test had reasonable sensitivities but low specificities for diagnosing COPD. HRCT has some additional advantages in detecting heterogeneity and concomitant lung diseases in COPD.     

Lung development and adult lung diseases

Adult respiratory diseases are caused by many factors, including genetic-environmental interaction. Genetic abnormalities can impact early fetal lung development, postnatal lung maturation, as well as adult lung injury and repair. Studies suggest that abnormally developed lung structure and function may contribute as a susceptibility factor for several adult lung diseases. This review focuses on the relationship between lung development and pathogenesis of several lung diseases including COPD, cystic fibrosis (CF), and asthma. COPD with emphysema has been considered to be an accelerated involutional disease of aging smokers. However, since only a proportion (approximately 15%) of smokers get COPD with emphysema, clearly genetic susceptibility must play a significant part in determining both the age of onset and the rapidity of decline in lung function. In mice, interference with key genes either by null mutation, hypomorphism, or gain or loss of function results in phenotypes comprising either neonatal lethal respiratory distress if the structural effect is severe, or reduced alveolarization and/or early onset emphysema if the effect is milder. Reported susceptibility candidate genes are therefore discussed in some detail, including elastin, lysyl oxidase, fibrillin, the transforming growth factor-beta-Smad3 pathway, as well as extracellular matrix proteases. In the case of CF, the Cftr gene has been shown to regulate fetal lung epithelial cell differentiation and maturation. Subtle abnormalities of lung structure and function are found in clinically asymptomatic CF infants. Finally, airway remodeling due to chronic inflammation is important in infants who later acquire asthma.     

Statement from the Japanese Respiratory Society: Working diagnosis and initial management of COPD during the COVID-19 pandemic

The Japanese Respiratory Society (JRS) has recommended spirometry for the diagnosis of respiratory diseases. It is indispensable for the confirmation of airflow obstruction by spirometry in chronic obstructive pulmonary disease (COPD) diagnosis. However, the coronavirus disease 2019 (COVID-19) pandemic has made it difficult for many clinics to perform spirometry as it may lead to possible aerosol infections. Thus, the diagnosis of COPD, especially in the early stage, has become difficult. To overcome this situation, JRS issued a “Flowchart of Working Diagnosis and Management of COPD during the COVID-19 Pandemic”. This flowchart may help physicians provisionally diagnose COPD patients without performing spirometry, offering them appropriate intervention even in epidemic and pandemic situations.     

Detection of previously undiagnosed cases of COPD in a high-risk population identified in general practice

Abstract Background and Aim: Under-diagnosis of COPD is a widespread problem. This study aimed to identify previously undiagnosed cases of COPD in a high-risk population identified through general practice. Methods: Participating GPs (n = 241) recruited subjects with no previous diagnosis of lung disease, >35 yrs, and at least one respiratory symptom. Age, smoking status, pack-years, BMI, dyspnoea score (MRC), and pre-bronchodilator spirometry data was obtained. Subjects with airway obstruction (FEV(1)/FVC ≤ 0.7) at initial spirometry were tested for reversibility, according to Danish COPD guidelines, with bronchodilator and, if necessary, corticosteroids in order to confirm a diagnosis of COPD. Results: A total of 4.049 (49% females) subjects were included; mean age 58 yrs, BMI 27, and 32 pack-years. The COPD prevalence was 21.7%; 8.3% in subjects younger than 48?years. Most patients were classified in GOLD stages I and II (36% and 50%, respectively). The number needed to screen (NNS) for a new diagnosis of COPD was 4.6. COPD diagnosis was related to gender, age, BMI (p < 0.001), pack-years, and cough (p < 0.001), wheezing (p < 0.001) and sputum production (p = 0.002). A threshold of 10% pre-test risk of COPD would have reduced the number of spirometry tests by 35% although 90% of the patients with COPD would still have been identified (NNS 3.9). Conclusions: Of the at-risk subjects studied, 22% were diagnosed with COPD. A case-finding strategy providing questionnaire assessment and diagnostic spirometry to high-risk subjects in primary care, and therefore, identifies a large proportion of undiagnosed COPD patients, especially in the early stages of the disease.     

Combined pulmonary fibrosis and emphysema: a distinct underrecognised entity.

The syndrome resulting from combined pulmonary fibrosis and emphysema has not been comprehensively described. The current authors conducted a retrospective study of 61 patients with both emphysema of the upper zones and diffuse parenchymal lung disease with fibrosis of the lower zones of the lungs on chest computed tomography. Patients (all smokers) included 60 males and one female, with a mean age of 65 yrs. Dyspnoea on exertion was present in all patients. Basal crackles were found in 87% and finger clubbing in 43%. Pulmonary function tests were as follows (mean+/-sd): total lung capacity 88%+/-17, forced vital capacity (FVC) 88%+/-18, forced expiratory volume in one second (FEV1) 80%+/-21 (% predicted), FEV1/FVC 69%+/-13, carbon monoxide diffusion capacity of the lung 37%+/-16 (% predicted), carbon monoxide transfer coefficient 46%+/-19. Pulmonary hypertension was present in 47% of patients at diagnosis, and 55% during follow-up. Patients were followed for a mean of 2.1+/-2.8 yrs from diagnosis. Survival was 87.5% at 2 yrs and 54.6% at 5 yrs, with a median of 6.1 yrs. The presence of pulmonary hypertension at diagnosis was a critical determinant of prognosis. The authors hereby individualise the computer tomography-defined syndrome of combined pulmonary fibrosis and emphysema characterised by subnormal spirometry, severe impairment of gas exchange, high prevalence of pulmonary hypertension, and poor survival.     

Prevalence of undiagnosed and undertreated chronic obstructive pulmonary disease in lung cancer population

Background and objective: Chronic obstructive pulmonary disease (COPD) is a risk factor and important coexisting disease for lung cancer; however, the current status of management of COPD in lung cancer patients is not fully described. This study addressed this issue in a general teaching hospital in China. Methods: Medical records of hospitalized lung cancer patients in Zhongshan Hospital, Fudan University, between January 2006 and December 2010 were reviewed. The definition of COPD was according to the spirometric criteria of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) document. The diagnostic rate (COPD recorded as a discharge diagnosis/spirometry‐defined percentage) and conformity to GOLD treatment guidelines were investigated. The factors influencing diagnosis were analysed. Results: During the study period, the prevalence of spirometry‐defined COPD in hospitalized lung cancer patients was 21.6% (705/3263). The overall diagnostic rate of COPD was 7.1%, and the treatment conformity for stable and acute exacerbation of COPD was 27.1% and 46.8%, respectively. Respiratory physicians had a higher diagnostic rate than non‐respiratory doctors (34.8% vs 2.9%, P < 0.001) and a better treatment conformity for acute exacerbation of COPD (63.6% vs 37.5%, P = 0.048). Patients with COPD as a discharge diagnosis had more chance to receive guideline‐consistent treatment. The diagnostic rate of COPD was higher among patients with a history of smoking, respiratory diseases or symptoms. Conclusions: COPD is substantially underdiagnosed and undertreated in a hospitalized lung cancer population. History of smoking, respiratory diseases and symptoms promotes diagnosis. Education of COPD knowledge among patients and doctors is urgently required in this special population.     

Lesser used tests of pulmonary function: compliance, resistance and dead space

The measurements of lung compliance, airway resistance and respiratory dead space as clinical tests have gradually fallen into disuse as the standard pulmonary function testing procedures; spirometry, lung volume and diffusing capacity measurement, followed, if necessary, by imaging have become the norm for diagnosis of COPD and other lung diseases. To have a real understanding of what spirometry and lung volume tests measure requires some knowledge of compliance and airway resistance. The respiratory dead space is an important global indicator of ventilation/perfusion relationships that remains of interest in the early detection of pulmonary emboli. There are other situations as well where it is clinically useful to perform the measurements described here, so these techniques, although generally set aside from the commonly used tests, should not be forgotten.     

Epidemiology of Chronic Obstructive Pulmonary Disease (COPD) in Aging Populations

Current epidemiologic practice evaluates COPD based on self-reported symptoms of chronic bronchitis, self-reported physician-diagnosed COPD, spirometry confirmed airflow obstruction, or emphysema diagnosed by volumetric computed chest tomography (CT). Because the highest risk population for having COPD includes a predominance of middle-aged or older persons, aging related changes must also be considered, including: 1) increased multimorbidity, polypharmacy, and severe deconditioning, as these identify mechanisms that underlie respiratory symptoms and can impart a complex differential diagnosis; 2) increased airflow limitation, as this impacts the interpretation of spirometry confirmed airflow obstruction; and 3) “senile” emphysema, as this impacts the specificity of CT-diagnosed emphysema. Accordingly, in an era of rapidly aging populations worldwide, the use of epidemiologic criteria that do not rigorously consider aging related changes will result in increased misidentification of COPD and may, in turn, misinform public health policy and patient care.     

Feasibility of spirometry and reversibility testing for the identification of patients with chronic obstructive pulmonary disease on asthma registers in general practice

There is renewed interest in the diagnosis of chronic obstructive pulmonary disease (COPD) within primary care. Primary care physicians have difficulty distinguishing asthma from COPD. We tested the feasibility of using spirometry and if appropriate, reversibility testing, to identify patients with COPD on asthma registers in primary care. We carried out a cross-sectional study in three inner-city group practices in east London. Three hundred and twenty-eight patients aged 50 years and over on practice asthma registers were invited to attend for spirometry and, if appropriate, a trial of oral corticosteroids. The main outcome measures were: feasibility of carrying out spirometry; lung function; severity of COPD; prior diagnosis of COPD; response to a corticosteroid trial; quality of life. One hundred and sixty-eight of 328 (51%) patients attended for spirometry. According to British Thoracic Society criteria, 58 (34%) patients had normal spirometry at the time of assessment; 40 (24%) had active asthma and 57 (34%) had COPD. Thirteen patients (8%) were unable to perform spirometry. Of 57 patients with COPD 30 (53%) had mild, 15 (26%) had moderate and 12 (21%) had severe disease. Twenty-three of 57 (40%) patients with COPD on spirometry had this diagnosis recorded prior to the study. New diagnoses of COPD were more likely in those with mild or moderate disease (P<0.05). Twenty-three of 57 (40%) patients with COPD completed a corticosteroid trial: one showed significant reversibility of lung function. Spirometry was feasible and helped identify patients with COPD on asthma registers in these inner-city practices. Patients aged 50 years and over on asthma registers had a wide spectrum of lung function with considerable diagnostic misclassification. Some patients with normal lung function when tested may have had well controlled asthma. New diagnoses of COPD were mainly in those with mild or moderate disease.     

Impact of COPD and emphysema on survival of patients with lung cancer: A meta‐analysis of observational studies

Both COPD and emphysema are associated with an increased incidence of lung cancer, but the impacts of these comorbidities on lung cancer prognosis are still unclear. Herein, we conducted a meta‐analysis to clarify whether the presence of these comorbidities indicates poor survival in patients with lung cancer. A comprehensive search was conducted using PubMed, Embase, Web of Science, ASCO Abstracts and Cochrane library for articles published before 1 June 2015. Papers referenced by the obtained articles were also reviewed. Main outcomes were overall survival (OS) and disease‐free survival (DFS) in patients with lung cancer. Pooled hazard ratio (HR) and 95% confidence intervals (CIs) were calculated using random‐effects models. Subgroup and sensitivity analyses were also conducted. Of 58 full texts reviewed, 26 met our inclusion criteria that were derived from 21 and seven studies examining the impacts of COPD and emphysema on survival of lung cancer, respectively. Meta‐analyses revealed that concomitant COPD was associated with poorer OS (HR, 1.17; 95% CI: 1.10–1.25, n = 20), which was independent of tumour staging, diagnostic criteria of COPD or location, and DFS (HR, 1.52; 95% CI: 1.04–2.23, n = 6) with high heterogeneity (I² = 78%). The presence of emphysema in patients with lung cancer predicted worse OS (HR, 1.66; 95% CI: 1.25–2.22, n = 7), but not poorer DFS. The presence of COPD and emphysema are robust predictors of poor survival in patients with lung cancer. Early detection of these diseases should be taken into account for lung cancer surveillance and management.     

Electrocardiographic changes in Emphysema

Chronic obstructive lung disease(COPD), predominantly emphysema, causes several thoracic anatomical and hemodynamic changes which may cause changes in various electrocardiographic parameters. A 12-lead electrocardiogram(ECG), which is often a part of routine evaluation in most clinical settings, may serve as a useful screening modality for diagnosis of COPD or emphysema. Our current article aims to provide a comprehensive review of the electrocardiographic changes encountered in COPD/emphysema utilizing published PubMed and Medline literature database. Several important ECG changes are present in COPD/emphysema and may serve as a good diagnostic tool. Verticalization of Pvector, changes in QRS duration, pattern recognition of precordial R-wave progression and axial shifts can be considered some of the most valuable markers among other changes. In conclusion, 12-lead surface electrocardiogram can serve as a valuable tool for the diagnosis of COPD and/or emphysema. An appropriate knowledge of these ECG changes can not only help in the diagnosis but can also immensely help in an appropriate clinical management of these patients.     

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.     

Regional Heterogeneity of Chronic Obstructive Pulmonary Disease Phenotypes: Pulmonary 3He Magnetic Resonance Imaging and Computed Tomography

Pulmonary ventilation may be visualized and measured using hyperpolarized ³He magnetic resonance imaging (MRI) while emphysema and its distribution can be quantified using thoracic computed tomography (CT). Our objective was to phenotype ex-smokers with COPD based on the apical-to-basal distribution of ventilation abnormalities and emphysema to better understand how these phenotypes change regionally as COPD progresses. We evaluated 100 COPD ex-smokers who provided written informed consent and underwent spirometry, CT and ³He MRI. ³He MRI ventilation imaging was used to quantify the ventilation defect percent (VDP) for whole-lung and individual lung lobes. Regional VDP was used to generate the apical-lung (AL)-to-basal-lung (BL) difference (ΔVDP); a positive ΔVDP indicated AL-predominant and negative ΔVDP indicated BL-predominant ventilation defects. Emphysema was quantified using the relative-area-of-the-lung ≤?950HU (RA₉₅₀) of the CT density histogram for whole-lung and individual lung lobes. The AL-to-BL RA₉₅₀ difference (ΔRA₉₅₀) was generated with a positive ΔRA₉₅₀ indicating AL-predominant emphysema and a negative ΔRA₉₅₀ indicating BL-predominant emphysema. Seventy-two ex-smokers reported BL-predominant MRI ventilation defects and 71 reported AL-predominant CT emphysema. BL-predominant ventilation defects (AL/BL: GOLD I = 18%/82%, GOLD II = 24%/76%) and AL-predominant emphysema (AL/BL: GOLD I = 84%/16%, GOLD II = 72%/28%) were the major phenotypes in mild-moderate COPD. In severe COPD there was a more uniform distribution for ventilation defects (AL/BL: GOLD III = 40%/60%, GOLD IV = 43%/57%) and emphysema (AL/BL: GOLD III = 64%/36%, GOLD IV = 43%/57%). Basal-lung ventilation defects predominated in mild-moderate GOLD grades, and a more homogeneous distribution of ventilation defects was observed in more advanced grade COPD; these differences suggest that over time, regional ventilation abnormalities become more homogenously distributed during disease progression.     

The nature and causes of chronic obstructive pulmonary disease: A historical perspective: The Christie Lecture 2007, Chicago, USA

Chronic obstructive pulmonary disease (COPD) is the currently favoured name for the diseases formerly known as emphysema and bronchitis. COPD has been recognized for more than 200 years. Its cardinal symptoms are cough, phlegm and dyspnea, and its pathology is characterized by enlarged airspaces and obstructed airways. In the 19th century, the diagnosis of COPD depended on its symptoms and signs of a hyperinflated chest, and reduced expiratory breath sounds. The airflow obstruction evident on spirometry was identified in that century, but did not enter into clinical practice. Bronchitis, and the mechanical forces required to overcome its obstruction, was believed to be responsible for emphysema, although the inflammation present was recognized. The causes of bronchitis, and hence emphysema, included atmospheric and domestic air pollution, as well as dusty occupations. Cigarette smoking only became recognized as the dominant cause in the 20th century. The lessons learned of the risks for COPD in 19th-century Britain are very pertinent to the world today.