Degree Of Airflow Limitation Research Articles

Comparison of GOLD classification and modified BODE index as staging systems of COPD

ObjectiveTo compare GOLD classification of COPD versus the modified BODE index as staging systems of COPD. BackgroundChronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation. The degree of airflow limitation was poorly predictive of dyspnea and quality of life. The BODE index was the first multidimensional assessment system for COPD. Cardiopulmonary exercise testing (CPET) is the most comprehensive, and correlates best with the symptoms of COPD. In this regard, two novel mBODE indices were constructed by replacing 6MWT with V̇O2 peak expressed either as the percentage of predicted values (mBODE%) or as the absolute values in ml/min/kg (mBODE). MethodsThis study included 28 patients with a wide range of severities of COPD. Cardiopulmonary exercise test and pulmonary functions were done. GOLD spirometric staging and combined assessment grouping were calculated then compared with the two mBODE indices. ResultsModerate agreement between the GOLD combined assessment grouping and GOLD spirometric staging systems and between mBODE and mBODE% in stratifying severity of COPD patients was observed. Evaluation of mBODE index as predictors of severity of COPD using GOLD spirometric staging as a diagnostic predictor of COPD revealed that mBODE index was 100% sensitive. However, 59.1% and 72.2% specificity were found for mBODE V̇O2ml/min/kg and mBODE V̇O2% predicted, respectively. ConclusionMultidimensional staging system taking into account the exercise pulmonary function tests is better than unidimensional systems based on the resting pulmonary function tests only. Therefore this suggests the need for integration of the novel multidimensional approach in the diagnostic guidelines of COPD.

Cognitive Functioning in Obstructive Lung Disease: Results from the United Kingdom Biobank

ObjectivesTo compare domains of cognitive functioning between persons with and without obstructive lung disease (OLD) and to analyze the relationship between cognitive functioning and the degree of airflow limitation. DesignAn observational population-based study. SettingThis research was conducted using the United Kingdom Biobank Resource. ParticipantsThe study population consisted of 43,039 persons with complete data on cognitive functioning and spirometry. MeasurementsCognitive functioning was compared between persons with and without OLD using linear regression analysis. The relationship between impairment in lung function and cognitive impairment was assessed among persons with OLD. ResultsPersons with OLD had significantly worse scores than persons without OLD on prospective memory [β = –0.15 (–0.22 to –0.09)], visuospatial memory [β round 1 = 0.06 (0.03‒0.10)]; β round 2 = 0.09 (<0.001‒0.18)), numeric short-term memory [β = ‒0.05 (‒0.10 to <0.001)] and cognitive processing speed [β = 4.62 (1.25‒8.01)] after correction for possible confounders. Impairment in prospective memory [β = 0.004 (<0.001‒0.01)] and numeric short-term memory [β = 0.01 (0.003‒0.01)] were weakly related to FEV1 (adjusted P < .05). ConclusionsPersons with OLD experience cognitive impairment in different domains, which is partially related to airway obstruction. In particular, memory and information processing are affected. Further assessment of the relationship with patient-related outcomes is needed to optimize patient-oriented treatment.

A study of diurnal variation in peak expiratory flow rates in healthy adult female subjects in South India

Background: Peak Expiratory Flow Rate (PEFR) reflects the strength and condition of respiratory muscles and the degree of airflow limitation in large airways. PEFR shows hour to hour variation that follows a specific pattern in asthmatics and healthy individuals. Adequate data is not available for the diurnal variation in normal individuals who are students in professional courses and had a sedentary life style. Hence, this study was undertaken to study the diurnal variation in peak expiratory flow rates in healthy adult female subjects in South India. Materials and Methods: Peak expiratory flow rate was recorded in 50 adult healthy female students aged 18-23 years and studying in professional courses. Mini Wright's peak flow meter was used to measure the peak expiratory flow rate. PEFR were recorded at 7-8 a.m., 10-11 a.m., 1-2 p.m., 4-5 p.m., and 7-8 p.m. for two consecutive days. Results: On analysis of PEFR records of individual subjects, it was seen that there was an overall dip in the morning at 7-8 h PEFR, which increased in the daytime, peaking in the afternoon at 1-2 p.m. and eventually decreased in the night. Subjects did not show the peak PEFR values at the same time point, 10% of subjects had a rise in PEFR in the early morning, afternoon (1-2 p.m.) peak was observed in 48% subjects and evening (4-5 p.m.) peak was observed in 16% subjects. 14% subjects showed a peak in the night time (7-8 p.m.) PEFR values. Conclusion: This study provided the preliminary reference data of diurnal variation of peak expiratory flow rate in healthy adults. Since, there is a variation in the peak expiratory flow rate recorded during different time points of the day; hence, to compare the PEFR between individuals it is advisable to record the PEFR at the same time point.

Vascular dysfunction in chronic obstructive pulmonary disease: current evidence and perspectives

The natural course of chronic obstructive pulmonary disease (COPD) is complicated by the development of systemic consequences and comorbidities. COPD has been associated with an increased risk for cardiovascular disease, osteoporosis, cachexia and skeletal muscle weakness. In several large prospective cohort studies, the degree of airflow limitation was an independent predictor of both fatal and nonfatal cardiovascular events, implying a causal relationship between airflow obstruction and vascular disease. The pathomechanisms responsible for this association are mostly unknown. It has been proposed that systemic inflammation, oxidative stress, hypoxia and sympathetic activation may be mechanisms in COPD leading to vascular dysfunction and cardiovascular disease. However, the current evidence of a causal relationship between COPD and vascular dysfunction is insufficient and more data from well-designed studies are urgently needed, hopefully leading to novel therapeutic and preventive approaches in the care of patients with COPD.

Cardiac Autonomic Function and Cardiovascular Response to Exercise in Patients with Chronic Obstructive Pulmonary Disease

Background: Chronic obstructive pulmonary disease (COPD) is associated with impaired exercise tolerance, but it has not been established to what extent cardiac autonomic function impacts on exercise capacity. Objective: To evaluate whether there is an association between airflow limitation and cardiac autonomic function and whether cardiac autonomic function plays a role in exercise intolerance and daily physical activity (PA) in patients with COPD. Methods: Univariate and multivariate analyses were performed to evaluate the association between both 6-minute walking test (6MWT) and PA (steps per day) and pulmonary function, cardiac autonomic function (HR at rest, HRR and heart rate variability, HRV) in patients with COPD. Results: In 154 COPD patients (87 females, mean [SD]: age 62.5 [10.7] years, FEV1%predicted (43.0 [19.2]%), mean HR at rest was elevated (86.4 [16.4] beats/min) and HRV was reduced (33.69 [28.96] ms) compared to published control data. There was a significant correlation between FEV1 and HR at rest (r = -0.32, p < 0.001), between HR at rest and 6MWD (r = -0.26, p = 0.001) and between HR at rest and PA (r = -0.29, p = 0.010). No correlation was found between HRV and 6MWD (r = 0.089, p = 0.262) and PA (r = 0.075, p = 0.322). In multivariate analysis both HR and FEV1 were independent predictors of exercise capacity in patients with COPD. Conclusions: In patients with COPD the degree of airflow limitation is associated with HR at rest. The degree of airflow limitation and cardiac autonomic function, as quantified by HR at rest, are independently associated with exercise capacity in patients with COPD.

Neurological and endocrinological disorders: orphans in chronic obstructive pulmonary disease

Patients with chronic obstructive pulmonary disease (COPD) are often characterised by a range of characteristic co-morbidities that interfere with their pulmonary disease. In addition to a mere association with co-morbidities, a complex pathophysiological interaction and mutual augmentation occurs between COPD and its co-morbidities that may result in disease progression and increased morbidity and mortality. An interdisciplinary approach is required both for diagnosis and treatment to target co-morbidities early in the course of the disease. This review summarizes the current knowledge of the interaction with cerebrovascular disease and endocrinological co-morbidities in COPD patients. There is growing evidence that COPD is an independent risk factor for ischemic stroke, increasing the risk about twofold. Stroke risk in COPD patients increases with the severity of the disease as measured by the degree of airflow limitation. The presence of cardiovascular risk factors is of particular importance for stroke prevention in COPD patients. Endocrinological co-morbidities are also important and many are associated with increased cardiovascular risk. Impaired glucose metabolism ranges from insulin resistance to overt diabetes mellitus, which is a frequent finding and is associated with worse outcome.

Perfused lung volume to thoracic gas volume ratio (perfused lung fraction) in patients with COPD and in controls

The deterioration of the ventilation-to-perfusion distribution in patients with chronic obstructive pulmonary disease (COPD) reflects structural changes affecting both the airways and the blood vessels. These changes result in lung perfusion abnormalities that may be quantified by lung perfusion single photon emission computed tomography (SPECT). To compare the perfused lung fraction (PLF) in patients with airflow obstruction and controls. Fourteen patients with COPD and 21 controls underwent spirometry, whole-body plethysmography, and lung perfusion SPECT. PLF was derived from the ratio of perfused lung volume (measured by SPECT) to thoracic gas volume (measured by whole-body plethysmography). In the whole study sample, there were 18 (51%) women and 17 (49%) men, mean age was 46.2 (±20.3) years, range: 18-80 years). In the COPD group, PLF was 0.74 (±0.08), whereas in the control group PLF was 0.99 (±0.18) (P<0.001). PLF correlated directly with forced expiratory volume in 1 s to forced vital capacity (r=0.597, P<0.001). Perfused lung volume was 3.66 (±0.64) l in the COPD group compared with 2.71 (±0.70) l in the control group (P<0.001). The fraction of lung volume receiving blood from the pulmonary artery is reduced in patients with COPD. The degree of underperfusion seems to correlate with the degree of airflow limitation.

Innate immune responses are increased in chronic obstructive pulmonary disease.

BackgroundChronic obstructive pulmonary disease (COPD) is characterised by irreversible airflow obstruction, neutrophilic airway inflammation and chronic bacterial colonisation, however the role of the innate immune response in the pathogenesis of COPD remains unclear.MethodsInduced sputum was obtained from adults with COPD (n = 22), and healthy controls (n = 29) and was processed for differential cell counts. The sputum supernatant was assayed for innate immune mediators using ELISA, whilst sputum gene expression was measured using real-time PCR. Peripheral blood neutrophils were isolated and their response to lipopolysaccaride (LPS) stimulation was assessed in a subgroup of participants with COPD (n = 13) and healthy controls (n = 21).ResultsParticipants with COPD had significantly higher protein levels of interleukin (IL)-8, and neutrophil elastase (NE) and detection of oncostatin M (OSM) compared to healthy controls. Gene expression for toll-like receptor (TLR) 2, IL-8 and OSM were also significantly higher in COPD participants. The level of IL-1β, surfactant protein (SP)-A, matrix metalloproteinase (MMP)-9 and TLR4 mRNA was not significantly different between groups. The level of innate immune response markers were highly associated with the presence of sputum neutrophils, each other and the degree of airflow limitation (FEV1/FVC). Peripheral blood neutrophils from participants with COPD had an increased response to stimulation by LPS; with a greater fold increase in the production of IL-8 and MMP-9 protein, and gene expression of IL-8, TLR2 and TLR4.ConclusionsThe innate immune response is increased in the airways and circulating neutrophils in COPD, and may be an important mechanism involved in disease pathogenesis.

Disproportionate Pulmonary Hypertension in a Patient with Early-onset Pulmonary Emphysema Treated with Specific Drugs for Pulmonary Arterial Hypertension

Severe pulmonary hypertension in chronic obstructive pulmonary disease (COPD) is referred to as 'disproportionate' because the elevated pulmonary artery pressure does not match the degree of air flow limitation. We report a 41-year-old man presenting with early-onset pulmonary emphysema and pulmonary hypertension with a mean pressure of 74 mmHg. Continuous intravenous epoprostenol led to marked hemodynamic improvement, and epoprostenol was successfully replaced with bosentan. The patient has been followed for 3 years without exacerbation. This is the first report demonstrating the long-term efficacy of specific drugs for pulmonary arterial hypertension in disproportionate pulmonary hypertension in COPD.

Immunohistochemical staining for transcription factor MafB in alveolar macrophages is correlated with spirometric measures of airflow limitation in smokers

Alveolar macrophages (AM) play an important role in the pathogenesis of COPD, and their numbers are significantly increased in patients with COPD. We previously demonstrated that expression of the transcription factor, MafB, was upregulated in AM of mice exposed to cigarette smoke. The aim of this study was to investigate whether the expression of MafB is associated with the degree of airflow limitation (AFL) in smokers. Lung tissue specimens were obtained from male patients undergoing resection of small peripheral lung tumours. The patients were classified into three groups according to smoking index and FEV1 /FVC: (i) non-smokers or non-heavy ex-smokers without AFL (FEV1 /FVC ≥ 0.7, smoking index ≤ 400) (n=8); (ii) heavy current smokers without AFL (FEV1 /FVC ≥ 0.7, smoking index ≥ 800) (n=8); and (iii) heavy current smokers with AFL (FEV1 /FVC < 0.6, smoking index ≥ 800) (n=8). The intensity of immunostaining for MafB in AM was quantified by image analysis. Immunostaining for MafB was significantly enhanced in AM of smokers with AFL compared with AM of subjects without AFL. Smoking index, FEV1/FVC and FEF(25-75%) (% predicted) were significantly correlated with the intensity of MafB immunostaining. Multiple linear regression analysis revealed that FEV1 % was also an independent negative predictor of the intensity of MafB immunostaining. The degree of immunostaining for MafB in AM was correlated with the degree of AFL in smokers. MafB may be involved in the pathophysiology of COPD.

Characterisation of COPD heterogeneity in the ECLIPSE cohort

BackgroundChronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations. This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE).MethodsWe studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers. In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography.ResultsCOPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function. Co-morbidities were more prevalent in COPD patients than in controls, and occurred to the same extent irrespective of the GOLD stage. The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, presence of co-morbidity, exercise capacity and number of exacerbations reported in the year before the study. The distribution of these variables within each GOLD stage was wide. Even in subjects with severe airflow obstruction, a substantial proportion did not report symptoms, exacerbations or exercise limitation. The amount of emphysema increased with GOLD severity. The prevalence of bronchiectasis was low (4%) but also increased with GOLD stage. Some gender differences were also identified.ConclusionsThe clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease.

Prognosis of COPD patients requiring frequent hospitalization: Role of airway infection

A subgroup of patients with chronic obstructive pulmonary disease require frequent hospitalization because of exacerbations of the disease. We hypothesized that airway infection by non-usual pathogens is a major factor driving hospitalization needs in these patients. 1) To describe the clinical and functional characteristics of a cohort of COPD patients requiring > or =2 hospitalizations per year; 2) to determine prospectively their microbiological pattern during exacerbations; and, 3) to analyze the prognostic value of several clinical, functional and microbiological variables with respect to hospitalizations and mortality. Open cohort study of 116 COPD patients who had been hospitalized at least twice during the last 12 months. Patients were followed for an average of 21 months. Clinical data, forced spirometry and 6min walking distance were determined, and the BODE index was calculated, at the time of inclusion in the study. During follow-up, sputum culture was obtained during exacerbations, and hospitalization and mortality were collected every two months. Mean age was 71 yrs, and 94% of patients were male. Main findings show that: 1) not all patients had severe disease according to either the degree of airflow limitation or the BODE index; 2) non-usual pathogens, mainly Pseudomonas aeruginosa, other gram-negative non-fermentative rods and Enterobacteriaceae, were isolated among 71.1% of the sputum obtained during exacerbations; and, 3) these pathogens were associated with poor prognosis and frequent hospitalization. Airway infection by non-usual pathogens appears to be a key driver of frequent hospitalizations and mortality in COPD.

Association of glutathione-S-transferase omega haplotypes with susceptibility to chronic obstructive pulmonary disease

Cigarette smoking is the main risk factor for developing the inflammatory lung disease chronic obstructive pulmonary disease (COPD). Differences in susceptibility among smokers have been attributed to a genetic predisposition. A recent publication on the Framingham Heart Study found a strong association of the Asn142Asp SNP in Glutatthione-S-transferase Omega (GSTO) 2 with forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC). FEV1 is the main parameter reflecting the degree of airflow limitation in patients with COPD. Therefore the present study was undertaken to investigate whether the Asn142Asp polymorphism in GSTO2 occurs more frequently in patients with COPD than healthy subjects and to replicate the finding that it strongly correlates with FEV1. Furthermore, the Ala140Asp substitution in GSTO1 was examined. Genotyping was carried out in 195 healthy controls and 355 patients with COPD. The results demonstrate that the Asn142Asp polymorphism in GSTO2 and the GSTO1140Asp/GSTO2142Asp haplotype were associated with increased risk of COPD. However, single-marker and haplotype-based analyses failed to reveal an association between lung function parameters and investigated non-synonymous coding SNPs in the GSTO genes. In conclusion, GSTO2 is a candidate gene for COPD, but is not associated with FEV1.

Study of the burden on patients with chronic obstructive pulmonary disease

Background:Health-related quality of life measures are widely used in patients with chronic obstructive pulmonary disease (COPD). However, they are extremely limited when used to evaluate patients outside the clinical trials. The aim of this study was to analyse the burden of the disease using a simple, validated, self-administered questionnaire specifically developed for patients in daily clinical practice.Methods:A total of 3935 patients (74.5% men; mean age, 67 years) participated in a cross-sectional study. The burden of COPD on patients was measured using the Clinical COPD Questionnaire (CCQ). COPD was rated at four levels by the forced expiratory volume in one second (FEV1) according to The Global Initiative for Chronic Obstructive Lung Disease (GOLD) scale.Results:The disease mainly affects old men (more than 50% were over 65 years of age) and non-employed men (23% were employed). Of the patients studied, 22.7% continued smoking, especially men (24.4% of men vs. 18.1% of women). Most patients (54%) were diagnosed with moderate stage II COPD. Severity of COPD was lower in women: 29.6% of men had severe COPD compared with 13.7% of women. During the last year, 65.1% had at least one acute exacerbation and 36.6% were admitted to hospital because of COPD exacerbation. No association was found between the body mass index and COPD stage. The variable that most influenced the disease burden was dyspnoea, as progression from grade 0 to grade 4 increased the disease burden by 1.78 points for symptoms, 2.43 for functional state and 1.53 for mental state. The functional classification of COPD also had a significant influence on the disease burden.Conclusions:The present findings show that dyspnoea and the degree of airflow limitation are the clinical variables that most affect the burden of COPD from the patient’s point of view.

Association of ex vivo vascular and bronchial dysfunctions in mild COPD

Background It has recently been shown that systemic endothelial dysfunction is associated with airflow limitation in COPD. We conducted this ex vivo study to assess whether endothelial dysfunction of pulmonary arteries of former smokers was associated with modifications of airway functions. Methods Pharmacological experiments were conducted on arterial and bronchial rings obtained from lung specimen of 20 patients with COPD (13 Gold class 0, 7 GOLD class I or IIA). The impairment of acetylcholine-mediated vasodilation (constriction) of preconstricted arterial rings defined endothelial dysfunction. Resting tone (initial and after a contraction test) and cGMP-mediated dilation of bronchial rings in response to zaprinast were evaluated. Results Initial airway resting tone was correlated with airflow limitation (FEV1 % predicted: Rho= −0.49; p=0.032). The acetylcholine response of arterial rings was correlated with zaprinast-induced bronchodilation (Rho=0.54, p=0.019). Patients with endothelial dysfunction (n=5), as compared with those displaying no dysfunction (n=15), were characterized by an increased resting tone (after contraction test), an impaired response to zaprinast but a similar degree of airflow limitation (FEV1). Conclusion Endothelial dysfunction of pulmonary arteries is associated with increased resting tone and impaired cGMP-mediated dilation of airways in former smokers, suggesting common underlying mechanisms of pulmonary arterial and bronchial dysfunctions.

CC Chemokine Receptor 5 and CXC Chemokine Receptor 6 Expression by Lung CD8 + Cells Correlates with Chronic Obstructive Pulmonary Disease Severity

Chronic obstructive pulmonary disease (COPD) is a progressive disease associated with a cellular inflammatory response. CD8(+) T cells are implicated in COPD pathogenesis, and their numbers significantly correlate with the degree of airflow limitation. Dendritic cells (DCs) are important sentinel immune cells, but little is known about their role in initiating and maintaining the CD8 T-cell response in COPD. To investigate the mechanisms for CD8(+) T-cell recruitment to the lung, we used resected human lung tissue to analyze chemokine receptor expression by CD8(+) T cells and chemokine production by CD1a(+) DCs. Among 11 surveyed chemokine receptors, only CC chemokine receptor (CCR5), CXC chemokine receptor (CXCR) 3, and CXCR6 correlated with COPD severity as defined by criteria from the Global Initiative for Chronic Obstructive Lung Disease. The CD8(+) T cells displayed a Tc1, CD45RA(+) effector memory phenotype. CD1a(+) DCs produced the respective ligands for CCR5 and CXCR3, CCL3 and CXCL9, and levels correlated with disease severity. CD1a(+) DCs also constitutively expressed the CXCR6 ligand, CXCL16. In conclusion, we have identified major chemokine elements that potentially mediate CD8(+) T-cell infiltration during COPD progression and demonstrated that CD1a(+) mucosal-associated DCs may sustain CD8(+) T-cell recruitment/retention. Chemokine targeting may prove to be a viable treatment approach.

From COPD to chronic systemic inflammatory syndrome?

797 Chronic obstructive pulmonary disease (COPD) is characterised by poorly reversible airfl ow limitation that is usually progressive and associated with an abnormal infl ammatory response of the lungs to noxious particles or gases, particularly cigarette smoke. 1 A diagnosis of COPD should be considered in any current or previous smoker older than 40 years who has symptoms of cough, sputum production, or dyspnoea. 1 Diagnosis and assessment of severity of COPD are based on the degree of airfl ow limitation at spirometry. 1 However, increasing evidence suggests that clinical features of COPD and airfl ow limitation are poorly correlated and a comprehensive approach, including imaging 2 and assessment of exercise tolerance and body-mass index, 3 is needed. In this Viewpoint, we aim to convey the message that COPD can no longer be judged a disease only of the lungs. We propose to add the term chronic systemic infl ammatory syndrome to the diagnosis of COPD to stimulate discussion around the frequent complex chronic comorbidities in people with COPD and to provoke a new view of the disease in general. Cigarette smoking is the major risk factor for COPD and is one of the most important risk factors for all chronic diseases and some cancers. 4

Characterisation of phenotypes based on severity of emphysema in chronic obstructive pulmonary disease

Background:Airflow limitation in chronic obstructive pulmonary disease (COPD) is caused by a mixture of small airway disease and emphysema, the relative contributions of which may vary among patients. Phenotypes of...

The FEV1/FEV6 ratio is a good substitute for the FEV1/FVC ratio in the elderly

To determine the agreement between the FEV1/FEV6 ratio and the FEV1/FVC ratio in an elderly population. The study sample consisted of 3874 participants in a cross-sectional population survey in Tromsö, Norway, aged 60 years or more, in whom acceptable spirometry had been obtained. Mean differences between the FEV1/FEV6 ratio (%) and the FEV1/FVC ratio (%) were calculated according to age, sex, smoking habit, and the degree of airflow limitation. ROC-curve analysis and Kappa-statistics were used to estimate the utility of the FEV1/FEV6 ratio in predicting an FEV1/FVC ratio < 70%. The mean difference between FEV1/FEV6% and FEV1/FVC% was 2.7% in both men and women. The difference between the two measures increased somewhat with increasing age, and was more pronounced with smoking and decreasing FEV1/FVC ratio. The value for the FEV1/FEV6 ratio which best predicted an FEV1/FVC ratio of 70%, was 73%, and a very good agreement was found between these two cut-off values (kappa = 0.86). The FEV1/FEV6 ratio appears to be a good substitute for the FEV1/FVC ratio in an elderly population.

Roger S. Mitchell Lecture. Chronic Obstructive Pulmonary Disease Phenotypes and Their Clinical Relevance

Phenotype is defined as the outward physical manifestation of patients with chronic obstructive pulmonary disease (COPD); anything that is part of their observable structure, function, or behavior. As such, for patients with COPD, the time has come to move from a disease expressed solely by the degree of airflow limitation, to a much broader and resourceful characterization of COPD. Recent advances in the detection of specific clinical phenotypes, such as persistent hypoxemia, hyperinflation with inhomogeneous emphysema, frequent exacerbators, and patients with peripheral muscle dysfunction, are resulting in specific forms of approaches to include therapy that are affecting outcomes. Further, the investigation of the differential influence of gender on the development of COPD is finally catching our attention. In the area of basic science, we are beginning to understand different expressions of disease through genomics, proteomics, and metabonomics. Extensions of these findings and that of neglected aspects that may explain the clinical course of certain patients, such as their psychologic background, will certainly increase our understanding and provide more solid scientific rationale to the phenotypic characterization of patients with COPD. Further, such understanding will not only help explain the manifestations and course of the disease in particular patients but also help select for specific therapies. The hope is that, coupled with primary and secondary prevention, we can reverse the current epidemic and we can improve the well-being of patients affected by COPD.