Sputum Biomarkers in Wood and Tobacco Smoke Etiotypes of Chronic Obstructive Pulmonary Disease.

Introduction: There is a need to better understand the etiotypes of chronic obstructive pulmonary disease (COPD) beyond the tobacco-smoke (TS-COPD). Wood smoke COPD (WS-COPD) is characterized by greater airway compromise, milder emphysema, and slower rate of lung function decline than TS-COPD. However, it is unclear if these two etiotypes of COPD have differences in sputum biomarker concentrations. Objective was to compare sputum levels of selected sputum biomarkers between WS-COPD and TS-COPD, and healthy controls. Methods: Eighty-eight women (69±12 years) were recruited and classified into: WS-COPD (n=31), TS-COPD (n=29) and controls (n=28). Using ELISA, we determined induced sputum levels of metalloproteinase 9 (MMP-9), chemokine ligand 5 (CCL5), interleukin-8 (IL-8), chemokine ligand 16 (CCL16/HCC-4) and vascular endothelial growth factor (VEGF-1). Differences were analyzed by Kruskal-Wallis and Mann-Whitney-U tests and correlation between airflow limitation and biomarkers by Spearman's test. Results: At similar degree of airflow obstruction, anthropometrics and medications use, the level of sputum CCL5 was higher in TS-COPD than WS-COPD (p=0.03) without differences in MMP-9, IL-8, CCL16/HCC-4, and VEGF-1. Women with WS-COPD and TS-COPD showed significantly higher sputum levels of MMP-9, IL-8 and CCL5 compared with controls (p<0.001). FEV1% predicted correlated negatively with levels of MMP-9 (rho:-0.26; P=0.016), CCL5 (rho:-0.37; P=0.001), IL-8 (rho:-0.42; P<0.001) and VEGF (rho:-0.22; P=0.04). Conclusion: While sputum concentrations of MMP-9, IL-8, and CCL5 were higher in COPD women compared with controls, women with TS-COPD had higher levels of CCL5 compared with those with WS-COPD. Whether this finding relates to differences in pathobiological pathways remains to be determined.

Study of the Direct Costs of Asthma at a Healthcare Service Provider in Bogotá, Colombia.

OBJECTIVES: This study aimed to describe clinical characteristics and direct medical costs associated with disease treatment in Colombia patients with asthma from 1 healthcare provider. METHODS: This was a descriptive study with a retrospective data collection from a healthcare provider's electronic medical records in Colombia. A clinical, demographic, and healthcare resource utilization profile was developed over a 12-month observation period after the identification of eligible patients. To determine the mean cost per patient per year, the total frequencies of resource utilization were added, and the result was multiplied by the unit cost of each of them. RESULTS: A total of 7919 patients were included in the analysis. The mean ± SD cost per patient per year ranged from $189.5 ± $1.900.6 to $240.2 ± $1.903.6 depending on the price guidebook. The total cost had been driven by the medication use (79% of total cost) and by the outpatient visits (20% of total cost). CONCLUSIONS: In the population analyzed, the mean total direct cost per patient per year of asthma was $189.5 and $240.2, depending on the cost source. Direct medical costs were higher in cases classified as severe and in the adult and elderly population. When comparing the sources of resource utilization, it was found that the mean cost per patient obtained from real-life data is lower than the theoretical cost obtained from the bottom-up method with quantification of resources from experts. It is important to consider limitations related to study design and the evolving landscape of asthma treatments.

Patterns and Trends in the Use of Medications for COPD Control in a Cohort of 9476 Colombian Patients, 2017-2019.

Purpose: Chronic obstructive pulmonary disease (COPD) affects approximately 174 million people worldwide. The objective was to determine the trends of COPD medication use in a group of Colombian patients. Patients and Methods: This was a retrospective study on prescription patterns of bronchodilators and other medications used in COPD from a population database with follow-up at 12 and 24 months. Patients older than 18 years of age of any sex with a COPD diagnostic code between 2017 and 2019 were included. Sociodemographic variables, medications, treatment schedules for COPD, comorbidities, comedications, and the specialty of the prescriber were considered. Results: Data from 9476 people with COPD was evaluated. The mean age was 75.9 ± 10.7 years, 50.1% were male, and 86.8% were prescribed by a general practitioner. A total of 57.9% had comorbidities, most often hypertension (44.4%). At the baseline measurement, on average, they received 1.6 medications/patient, mainly short-acting antimuscarinics (3784; 39.9%), followed by short-acting ß-agonists (2997, 31.6%) and inhaled corticosteroids (ICS) (2239, 23.6%); more than half (5083, 53.6%) received a long-acting bronchodilator. Prescription of triple therapy (antimuscarinic, ß-agonist, and ICS) went from 645 (6.8%) at baseline to 1388 (20.6%) at the 12-month mark. Conclusion: This group of patients with COPD treated in Colombia frequently received short-acting bronchodilators and ICS, but a growing proportion are undergoing controlled therapy with long-acting bronchodilators, a situation that can improve the indicators of morbidity, exacerbations, and hospitalization.

Smoking cessation and vaccination.

A significant proportion of COPD patients (∼40%) continue smoking despite knowing that they have the disease. Smokers with COPD exhibit higher levels of nicotine dependence, and have lower self-efficacy and self-esteem, which affects their ability to quit smoking. Treatment should be adapted to the needs of individual patients with different levels of tobacco dependence. The combination of counselling plus pharmacotherapy is the most effective cessation treatment for COPD. In patients with severe COPD, varenicline and bupropion have been shown to have the highest abstinence rates compared with nicotine replacement therapy. There is a lack of evidence to support that smoking cessation reduction or harm reduction strategies have benefits in COPD patients. The long-term efficacy and safety of electronic cigarettes for smoking cessation need to be evaluated in high-risk populations; therefore, it is not possible to recommend their use for smoking cessation in COPD. Future studies with the new generation of nicotine vaccines are necessary to determine their effectiveness in smokers in general and in COPD patients.

CC16 augmentation reduces exaggerated COPD-like disease in Cc16-deficient mice.

Low Club Cell 16 kDa protein (CC16) plasma levels are linked to accelerated lung function decline in patients with chronic obstructive pulmonary disease (COPD). Cigarette smoke-exposed (CS-exposed) Cc16-/- mice have exaggerated COPD-like disease associated with increased NF-κB activation in their lungs. It is unclear whether CC16 augmentation can reverse exaggerated COPD in CS-exposed Cc16-/- mice and whether increased NF-κB activation contributes to the exaggerated COPD in CS-exposed Cc16-/- lungs. CS-exposed WT and Cc16-/- mice were treated with recombinant human CC16 (rhCC16) or an NF-κB inhibitor versus vehicle beginning at the midpoint of the exposures. COPD-like disease and NF-κB activation were measured in the lungs. RhCC16 limited the progression of emphysema, small airway fibrosis, and chronic bronchitis-like disease in WT and Cc16-/- mice partly by reducing pulmonary inflammation (reducing myeloid leukocytes and/or increasing regulatory T and/or B cells) and alveolar septal cell apoptosis, reducing NF-κB activation in CS-exposed Cc16-/- lungs, and rescuing the reduced Foxj1 expression in CS-exposed Cc16-/- lungs. IMD0354 treatment reduced exaggerated lung inflammation and rescued the reduced Foxj1 expression in CS-exposed Cc16-/- mice. RhCC16 treatment reduced NF-κB activation in luciferase reporter A549 cells. Thus, rhCC16 treatment limits COPD progression in CS-exposed Cc16-/- mice partly by inhibiting NF-κB activation and represents a potentially novel therapeutic approach for COPD.

Utilization Patterns and Trends in the Use of Medications for Asthma in a Cohort of Colombian Patients.

Purpose: Asthma affects approximately 358 million people worldwide. This study aimed to determine the trend for the use of medications intended to treat asthma in a group of patients affiliated with the Colombian health system. Patients and Methods: This was a retrospective study on prescription patterns of medications used to treat asthma in patients over 5 years of age between 2017 and 2019. Sociodemographic variables, medications used and combinations, the persistence of use, and prescribing physicians were considered. Data were obtained from a drug-dispensing database from Colombia. Results: A total of 10,706 people diagnosed with asthma were identified, including predominantly females (56.8%), with a mean age of 32.2 ± 26.1 years. At the beginning of the follow-up, 53.2% of patients aged 5-11 years were receiving monotherapy, with a mean of 1.5 ± 0.6 drugs/patient, especially inhaled corticosteroids (ICSs; 55.9%) and short-acting ß-agonists (SABAs; 55.6%). Moreover, in patients older than 12 years, 53.5% were treated with monotherapy, with a mean of 1.6 ± 0.7 drugs/patient, 45.9% of whom were on SABAs, while 37.1% were on ICSs. Between 63.0% and 83.6% of patients were treated by a general practitioner. 12.5% of patients (n = 495) received triple therapy (ICS/LABA + LAMA [long-acting antimuscarinic]), particularly fluticasone/salmeterol + tiotropium. Conclusion: The identification of treatment patterns will allow physicians and decision makers to implement strategies in order to promote adherence to treatment and improve asthma medication use.

Early diagnosis of COPD: myth or a true perspective.

The early stages of COPD have recently become a hot topic as many new risk factors have been proposed, but substantial knowledge gaps remain in explaining the natural history of the disease. If we are to modify the outcomes of COPD, early detection needs to play a critical role. However, we need to sort out the barriers to early detection and have a better understanding of the definition of COPD and its diagnosis and therapeutic strategies to identify and treat patients with COPD before structural changes progress. In this review, we aim to clarify the differences between early COPD, mild COPD and early detection of COPD, with an emphasis on the clinical burden and how different outcomes (quality of life, exacerbation, cost and mortality) are modified depending on which definition is used. We will summarise the evidence for the new multidimensional diagnostic approaches to detecting early pathophysiologic changes that potentially allow for future studies on COPD management strategies to halt or prevent disease development.

Club cell protein 16 (Cc16) deficiency increases inflamm-aging in the lungs of mice.

Low serum CC16 levels are associated with accelerated lung function decline in human population studies, but it is not known whether low serum CC16 levels contribute to lung function decline, or are an epiphenomenon. We tested the hypothesis that unchallenged Cc16-/- mice develop accelerated rates of pulmonary function test abnormalities and pulmonary pathologies over time compared with unchallenged WT mice. Respiratory mechanics, airspace enlargement, and small airway fibrosis were measured in unchallenged wild-type (WT) versus Cc16-/- mice over 6-18 months of age. Lung leukocyte counts and lung levels of metalloproteinases (Mmps), cytokines, oxidative stress, cellular senescence markers (p19 and p21), and lung cell apoptosis, and serum C-reactive protein (CRP) levels were measured in age-matched WT versus Cc16-/- mice. Unchallenged Cc16-/- mice developed greater increases in lung compliance, airspace enlargement, and small airway fibrosis than age-matched WT mice over 6-18 months of age. Cc16-/- mice had greater: (1) lung leukocyte counts; (2) lung levels of Ccl2, Ccl-5, interleukin-10, Mmp-2, and Mmp-9; (3) pulmonary oxidative stress levels, (4) alveolar septal cell apoptosis and staining for p16 and p21; and (5) serum CRP levels. Unchallenged Cc16-/- mice had greater nuclear factor-κB (NF-κB) activation in their lungs than age-matched WT mice, but similar lung levels of secretory phospholipase-A2 activity. Cc16 deficiency in mice leads spontaneously to an accelerated lung aging phenotype with exaggerated pulmonary inflammation and COPD-like lung pathologies associated with increased activation of NF- κB in the lung. CC16 augmentation strategies may reduce lung aging in CC16-deficient individuals.

Is It Time to Change the Definition of Acute Exacerbation of Chronic Obstructive Pulmornary Disease? What Do We Need to Add?

Acute exacerbations in chronic obstructive pulmonary disease (AECOPD) are associated with increased mortality, rate of hospitalization, use of healthcare resources, and have a negative impact on disease progression, quality of life and lung function of patients with chronic obstructive pulmonary disease (COPD). There is an imperative need to homogenize the definition of AECOPD because the incidence of exacerbations has a significant influence or implication on treatment decision making, particularly in pharmacotherapy and could impact the outcome or change the statistical significance of a therapeutic intervention in clinical trials. In this review, using PubMed searches, we have analyzed the weaknesses and strengths of the different used AECOPD definitions (symptom-based, healthcare-based definition or the combinations of both), as well as the findings of the studies that have assessed the relationship of different biomarkers with the diagnosis, etiology and differential diagnosis of AECOPD and the progress towards the development of a more precise definition of COPD exacerbation. Finally, we have proposed a simple definition of AECOPD, which must be validated in future clinical trials to define its accuracy and usefulness in daily practice.

Smoke, Biomass Exposure, and COPD Risk in the Primary Care Setting: The PUMA Study.

BACKGROUND: The evidence indicates that risk factors other than smoking are important in the development of COPD. It has been postulated that less traditional risk factors (eg, exposure to coal and/or biomass smoke) may interact with smoking to further increase COPD risk. This analysis evaluated the effect of exposure to biomass and smoking on COPD risk in a primary care setting in Latin America. METHODS: Subjects attending routine primary care visits, ≥40 y old, who were current or former smokers or were exposed to biomass smoke, completed a questionnaire and performed spirometry. COPD was defined as post-bronchodilator FEV1/FVC < 0.70 and the lower limit of normal. Smoking was defined by pack-years (≤ 20, 20-30, or > 30), and biomass exposure was defined as an exposure to coal or wood (for heating, cooking, or both) for ≥ 10 y. RESULTS: One thousand seven hundred forty-three individuals completed the questionnaire, and 1,540 performed spirometry. Irrespective of COPD definition, approximately 40% of COPD subjects reported exposure to biomass versus 30% of those without COPD. A higher proportion of COPD subjects (post-bronchodilator FEV1/FVC < 0.70) than those without COPD smoked > 30 pack-years (66% vs 39%); similar results were found with the lower limit of normal definition. Analysis of exposure to biomass > 10 y plus smoking > 20 pack-years (reference was no exposure) found that tobacco smoking (crude odds ratio [OR] 4.50, 95% CI 2.73-7.41; adjusted OR 3.30, 95% CI 1.93-5.63) and biomass exposure (crude OR 3.66, 95% CI 2.00-6.73; adjusted OR 2.28, 95% CI 1.18-4.41) were risk factors for COPD, with smoking a possible confounder for the association between biomass and COPD (post-bronchodilator FEV1/FVC < 0.70); similar results were found with the lower limit of normal definition. CONCLUSIONS: Subjects with COPD from primary care had a higher exposure to biomass and smoking compared with non-COPD subjects. Smoking and biomass are both risk factors for COPD, but they do not appear to have an additive effect.

Asthma-COPD overlap syndrome (ACOS) in primary care of four Latin America countries: the PUMA study.

BACKGROUND: Asthma-COPD overlap syndrome (ACOS) prevalence varies depending on the studied population and definition criteria. The prevalence and clinical characteristics of ACOS in an at-risk COPD primary care population from Latin America was assessed. METHODS: Patients ≥40 years, current/ex-smokers and/or exposed to biomass, attending routine primary care visits completed a questionnaire and performed spirometry. COPD was defined as post-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) < 0.70; asthma was defined as either prior asthma diagnosis or wheezing in the last 12 months plus reversibility (increase in post-bronchodilator FEV1 or FVC ≥200 mL and ≥12%); ACOS was defined using a combination of COPD with the two asthma definitions. Exacerbations in the past year among the subgroups were evaluated. RESULTS: One thousand seven hundred forty three individuals completed the questionnaire, 1540 performed acceptable spirometry, 309 had COPD, 231 had prior asthma diagnosis, and 78 asthma by wheezing + reversibility. ACOS prevalence in the total population (by post-bronchodilator FEV1/FVC < 0.70 plus asthma diagnosis) was 5.3 and 2.3% by post-bronchodilator FEV1/FVC < 0.70 plus wheezing + reversibility. In the obstructive population (asthma or COPD), prevalence rises to 17.9 and 9.9% by each definition, and to 26.5 and 11.3% in the COPD population. ACOS patients defined by post-bronchodilator FEV1/FVC < 0.7 plus wheezing + reversibility had the lowest lung function measurements. Exacerbations for ACOS showed a prevalence ratio of 2.68 and 2.20 (crude and adjusted, p < 0.05, respectively) (reference COPD). CONCLUSIONS: ACOS prevalence in primary care varied according to definition used. ACOS by post-bronchodilator FEV1/FVC < 0.7 plus wheezing + reversibility represents a clinical phenotype with more frequent exacerbations, which is probably associated with a different management approach.

Clasificación de los pacientes con enfermedad pulmonar obstructiva crónica según los sistemas de estadificación de la Asociación Latinoamericana de Tórax (ALAT) y la iniciativa global para la enfermedad pulmonar obstructiva crónica (GOLD) / Classification of patients with chronic obstructive pulmonary disease according to the Latin American Thoracic Association (ALAT) staging systems and the global initiative for chronic obstructive pulmonary disease (GOLD)

Introducción. En los diferentes sistemas de clasificación de la EPOC se utilizan diversos criterios de estadificación. El objetivo de este estudio fue comparar la prevalencia y la distribución de los estadios de la EPOC con las recomendaciones de la iniciativa global para la enfermedad pulmonar obstructiva crónica (GOLD) y las orientaciones de la Asociación Latinoamericana de Tórax (ALAT) en una población de atención primaria. Métodos. Sujetos ≥ 40 años de edad, fumadores, exfumadores o expuestos a biomasa que acudieron a visitas rutinarias en centros de atención primaria cumplimentaron un cuestionario y se sometieron a una espirometría. Se definió EPOC si el cociente FEV1/FVC era < 0,70 tras la administración de un broncodilatador, y se calificó de acuerdo con los criterios GOLD-2013 y ALAT-2014. El valor pronóstico de los sistemas de estratificación se evaluó mediante el índice BODEx. Resultados. Cumplimentaron la entrevista 1.743 pacientes, de los cuales 1.540 obtuvieron espirometrías aceptables. Según los criterios GOLD-2013 la prevalencia de EPOC fue de un 20,1% y la distribución de estadios fue en forma de U (grupo A: 9,3%, B: 4,3%, C: 2,0% y D: 4,6%). Con los criterios de las orientaciones ALAT la prevalencia fue de un 19,7%, con una distribución de estadios en forma de campana (leve: 2,9%, moderada: 9%, grave: 5,4% y muy grave: 2,7%). Al utilizar las orientaciones de la ALAT, aproximadamente un 73% de los pacientes fue adjudicado a los estratos de EPOC moderada (45,4%) o grave (27,3%), mientras que con los criterios GOLD-2013 la mayoría (aproximadamente un 69%) se clasificó en los grupos A (46,3%) y B (22,7%). Con la estratificación ALAT las puntuaciones del índice BODEx aumentaron al empeorar la EPOC, lo que no se observó con los criterios GOLD-2013 (los valores de los grupos B y C fueron similares). Conclusiones. La distribución de pacientes en los estadios de la enfermedad difiere según se usen los criterios de la ALAT o GOLD-2013. Los criterios de la ALAT identificaron una mayor proporción de pacientes en las categorías moderada y grave de EPOC que los criterios GOLD-2013, con los cuales la mayoría de pacientes fueron adjudicados al grupo A. En futuras evaluaciones de la clasificación ALAT se debería analizar su capacidad predictiva de hospitalizaciones y mortalidad

Introduction. Several classification systems use different criteria when assessing COPD stages. The objective of this study was to compare the prevalence and distribution of COPD stagesusing Global initiative for chronic Obstructive Lung Disease (GOLD) recommendationsand Latin American Thoracic Association (ALAT) guidelinesin a primary-care population. Methods. Subjects attending routine primary care visits, ≥ 40 years of age, current or former smokers or exposed to biomass, completed a questionnaire and performed spirometry. COPD was defined as post-bronchodilator FEV1/FVC < 0.70 and categorised according to GOLD-2013 criteria and ALAT-2014 guideline. The BODEx index was used to assess the prognostic value of the stratification systems. Results. A total of 1743 subjects completed the interview, 1540 performed acceptable spirometry. COPD prevalence according GOLD-2013 was 20.1% and had a U-shaped stage distribution (group A: 9.3%, B: 4.3%, C: 2.0%, D: 4.6%). According to ALAT, prevalence was 19.7% with a bell-shaped stage distribution (mild: 2.9%, moderate: 9%, severe: 5.4%, very-severe: 2.7%). Approximately 73% of patients were stratified as moderate (45.4%) or severe (27.3%) by ALAT guidelines, whereas using GOLD-2013 criteria the majority of subjects (approximately 69%) were in group A (46.3%) or group B (22.7%). BODE index score increased as COPD worsened according to ALAT stratification. This is not observed with GOLD2013 criteria (similar values for B and C groups). Conclusions. Disease stages differ under ALAT and GOLD-2013 criteria. ALAT identified a greater proportion of COPD subjects in the moderate and severe categories compared with GOLD-2013, where the majority were categorised in group A. Future evaluation of the ALAT classification should address its predictive ability in terms of hospitalizations and mortality

A Pilot Study Linking Endothelial Injury in Lungs and Kidneys in Chronic Obstructive Pulmonary Disease.

RATIONALE: Patients with chronic obstructive pulmonary disease (COPD) frequently have albuminuria (indicative of renal endothelial cell injury) associated with hypoxemia. OBJECTIVES: To determine whether (1) cigarette smoke (CS)-induced pulmonary and renal endothelial cell injury explains the association between albuminuria and COPD, (2) CS-induced albuminuria is linked to increases in the oxidative stress-advanced glycation end products (AGEs) receptor for AGEs (RAGE) pathway, and (3) enalapril (which has antioxidant properties) limits the progression of pulmonary and renal injury by reducing activation of the AGEs-RAGE pathway in endothelial cells in both organs. METHODS: In 26 patients with COPD, 24 ever-smokers without COPD, 32 nonsmokers who underwent a renal biopsy or nephrectomy, and in CS-exposed mice, we assessed pathologic and ultrastructural renal lesions, and measured urinary albumin/creatinine ratios, tissue oxidative stress levels, and AGEs and RAGE levels in pulmonary and renal endothelial cells. The efficacy of enalapril on pulmonary and renal lesions was assessed in CS-exposed mice. MEASUREMENTS AND MAIN RESULTS: Patients with COPD and/or CS-exposed mice had chronic renal injury, increased urinary albumin/creatinine ratios, and increased tissue oxidative stress and AGEs-RAGE levels in pulmonary and renal endothelial cells. Treating mice with enalapril attenuated CS-induced increases in urinary albumin/creatinine ratios, tissue oxidative stress levels, endothelial cell AGEs and RAGE levels, pulmonary and renal cell apoptosis, and the progression of chronic renal and pulmonary lesions. CONCLUSIONS: Patients with COPD and/or CS-exposed mice have pulmonary and renal endothelial cell injury linked to increased endothelial cell AGEs and RAGE levels. Albuminuria could identify patients with COPD in whom angiotensin-converting enzyme inhibitor therapy improves renal and lung function by reducing endothelial injury.

Classification of patients with chronic obstructive pulmonary disease according to the Latin American Thoracic Association (ALAT) staging systems and the global initiative for chronic obstructive pulmonary disease (GOLD). / Clasificación de los pacientes con enfermedad pulmonar obstructiva crónica según los sistemas de estadificación de la Asociación Latinoamericana de Tórax (ALAT) y la iniciativa global para la enfermedad pulmonar obstructiva crónica (GOLD).

INTRODUCTION: Several classification systems use different criteria when assessing COPD stages. The objective of this study was to compare the prevalence and distribution of COPD stagesusing Global initiative for chronic Obstructive Lung Disease (GOLD) recommendationsand Latin American Thoracic Association (ALAT) guidelinesin a primary-care population. METHODS: Subjects attending routine primary care visits, ≥40 years of age, current or former smokers or exposed to biomass, completed a questionnaire and performed spirometry. COPD was defined as post-bronchodilator FEV1/FVC<0.70 and categorised according to GOLD-2013 criteria and ALAT-2014 guideline. The BODEx index was used to assess the prognostic value of the stratification systems. RESULTS: A total of 1743 subjects completed the interview, 1540 performed acceptable spirometry. COPD prevalence according GOLD-2013 was 20.1% and had a U-shaped stage distribution (group A: 9.3%, B: 4.3%, C: 2.0%, D: 4.6%). According to ALAT, prevalence was 19.7% with a bell-shaped stage distribution (mild: 2.9%, moderate: 9%, severe: 5.4%, very-severe: 2.7%). Approximately 73% of patients were stratified as moderate (45.4%) or severe (27.3%) by ALAT guidelines, whereas using GOLD-2013 criteria the majority of subjects (approximately 69%) were in group A (46.3%) or group B (22.7%). BODE index score increased as COPD worsened according to ALAT stratification. This is not observed with GOLD2013 criteria (similar values for B and C groups). CONCLUSIONS: Disease stages differ under ALAT and GOLD-2013 criteria. ALAT identified a greater proportion of COPD subjects in the moderate and severe categories compared with GOLD-2013, where the majority were categorised in group A. Future evaluation of the ALAT classification should address its predictive ability in terms of hospitalizations and mortality.

Exacerbations and health care resource utilization in patients with airflow limitation diseases attending a primary care setting: the PUMA study.

BACKGROUND: COPD, asthma, and asthma-COPD overlap increase health care resource consumption, predominantly because of hospitalization for exacerbations and also increased visits to general practitioners (GPs) or specialists. Little information is available regarding this in the primary care setting. OBJECTIVES: To describe the prevalence and number of GP and specialist visits for any cause or due to exacerbations in patients with COPD, asthma, and asthma-COPD overlap. METHODS: COPD was defined as post-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio <0.70; asthma was defined as prior medical diagnosis, wheezing in the last 12 months, or wheezing plus reversibility (post-bronchodilator FEV1 or FVC increase ≥200 mL and ≥12%); asthma-COPD overlap was defined as post-bronchodilator FEV1/FVC <0.70 plus prior asthma diagnosis. Health care utilization was evaluated as GP and/or specialist visits in the previous year. RESULTS: Among the 1,743 individuals who completed the questionnaire, 1,540 performed acceptable spirometry. COPD patients had a higher prevalence of any medical visits to any physician versus those without COPD (37.2% vs 21.8%, respectively) and exacerbations doubled the number of visits. The prevalence of any medical visits to any physician was also higher in asthma patients versus those without asthma (wheezing: 47.2% vs 22.7%; medical diagnosis: 54.6% vs 21.6%; wheezing plus reversibility: 46.2% vs 23.8%, respectively). Asthma patients with exacerbations had twice the number of visits versus those without an exacerbation. The number of visits was higher (2.8 times) in asthma-COPD overlap, asthma (1.9 times), or COPD (1.4 times) patients versus those without these respiratory diseases; the number of visits due to exacerbation was also higher (4.9 times) in asthma-COPD overlap, asthma (3.5 times), and COPD (3.8 times) patients. CONCLUSION: COPD, asthma, and asthma-COPD overlap increase the prevalence of medical visits and, therefore, health care resource utilization. Attempts to reduce health care resource use in these patients require interventions aimed at preventing exacerbations.

Asthma COPD Overlap Syndrome: An Approach to A Real -World Endotype in Obstructive Lung Disease?

BACKGROUND: Although some patients with obstructive lung disease (OLD) have features of both asthma and chronic obstructive pulmonary disease (COPD), the term "asthma-COPD overlap syndrome (ACOS)" was coined only relatively recently. However, there are gaps in our knowledge of the clinical features, pathogenesis, prognosis, and management of ACOS patients. OBJECTIVES: To review the literature on ACOS to determine the extent to which the clinical features, pathologic mechanisms, clinical outcomes, and current therapeutic approaches for ACOS differ from those in patients with asthma alone or COPD alone. METHODS: PUBMED searches were conducted to review the demographic and clinical features, comorbidities, lung imaging characteristics, prognoses, pathologic mechanisms, and current therapeutic approaches for patients with ACOS versus asthma alone or COPD alone. RESULTS: Criteria that are used to diagnose ACOS vary considerably. Overall, ACOS patients have higher symptom burdens (especially dyspnea), poorer quality of life scores, and more frequent and severe exacerbations than patients with COPD alone or asthma alone. However, there are conflicting reports on the prognosis of ACOS patients. Imaging studies indicate that ACOS is predominantly an airway disease. ACOS has been linked to the presence of Th2-type immune responses in COPD airways and Th1-type immune responses in asthmatic airways. Current therapeutic options for ACOS patients include inhaled corticosteroids and bronchodilators. However, randomized clinical trials have not yet been conducted to optimize the management of ACOS patients. CONCLUSION: ACOS patients have clinical features that are now well defined, but additional studies are needed to provide novel insights into ACOS pathogenesis, and to optimize the treatment of these patients.

Hhip haploinsufficiency sensitizes mice to age-related emphysema.

Genetic variants in Hedgehog interacting protein (HHIP) have consistently been associated with the susceptibility to develop chronic obstructive pulmonary disease and pulmonary function levels, including the forced expiratory volume in 1 s (FEV1), in general population samples by genome-wide association studies. However, in vivo evidence connecting Hhip to age-related FEV1 decline and emphysema development is lacking. Herein, using Hhip heterozygous mice (Hhip(+/-)), we observed increased lung compliance and spontaneous emphysema in Hhip(+/-) mice starting at 10 mo of age. This increase was preceded by increases in oxidative stress levels in the lungs of Hhip(+/-) vs. Hhip(+/+) mice. To our knowledge, these results provide the first line of evidence that HHIP is involved in maintaining normal lung function and alveolar structures. Interestingly, antioxidant N-acetyl cysteine treatment in mice starting at age of 5 mo improved lung function and prevented emphysema development in Hhip(+/-) mice, suggesting that N-acetyl cysteine treatment limits the progression of age-related emphysema in Hhip(+/-) mice. Therefore, reduced lung function and age-related spontaneous emphysema development in Hhip(+/-) mice may be caused by increased oxidative stress levels in murine lungs as a result of haploinsufficiency of Hhip.

Increased expression of A Proliferation-inducing Ligand (APRIL) in lung leukocytes and alveolar epithelial cells in COPD patients with non small cell lung cancer: a possible link between COPD and lung cancer?

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterized by an excessive activation of the adaptive immune system and, in particular, uncontrolled expansion of the B-cell pool. One of the key promoters of B cell expansion is A PRoliferation-Inducing Ligand (APRIL). APRIL has been strongly linked to non small cell lung cancer (NSCLC) onset and progression previously. However, little is known about the expression of APRIL in the lungs of COPD patients. METHODS: Using immuno-fluorescence staining, the expression of APRIL was assessed in sections of lungs from 4 subjects with primary diagnosis of COPD (FEV1 33 ± 20 % predicted), 4 subjects with primary diagnosis of NSCLC, 4 subjects diagnosed with both COPD and NSCLC, smokers without COPD or NSCLC and 3 healthy never-smokers. The percentage of B cells, alveolar macrophages (AMs) and polymorphonuclear neutrophils (PMNs) in the lung and alveolar epithelial cells (AECs) that stained positively for APRIL was quantified using epi-fluorescence microscopy and image analysis software. RESULTS: The percentage of APRIL-expressing B cells, AMs, PMNs and alveolar epithelial cells (AECs) was higher in patients having both COPD and NSCLC than in patients with either COPD or NSCLC alone, SC or NSC (p < 0.03 for all comparisons). The percentage of APRIL-expressing AMs and AECs (but not in B cells) was higher in patients with NSCLC alone than in patients with COPD alone. The percentage of APRIL-expressing AECs (but not B cells or AMs) was higher in COPD patients than in SC and NSC (p < 0.05 for all comparisons). The percentage of APRIL-expressing B cells, AMs and AECs cells was similar in NSC and SC. CONCLUSION: The percentage of APRIL-expressing B cells, AMs and AECs is higher in the lungs of patients with both COPD and NSCLC than in patients with COPD or NSCLC alone or control subjects. These findings suggest that APRIL may contribute to the pathogenesis of both COPD and NSCLC, and possibly to the development of NSCLC in patients with established COPD.