Determinants in the Underdiagnosis of COPD in Spain—CONOCEPOC Study

Respiratory symptoms; Spirometry; UnderdiagnosisSíntomas respiratorios; Espirometría; InfradiagnósticoSímptomes respiratoris; Espirometria; InfradiagnòsticFactors such as seeking medical attention for respiratory symptoms and health professionals ordering spirometry come into play in the underdiagnosis of chronic obstructive pulmonary disease (COPD). The objective of this study was to analyze seeking medical attention and the use of spirometry in individuals with chronic respiratory symptoms and to compare these results with those obtained in the 2005 and 2011 surveys. Material and Methods: A cross-sectional, observational, epidemiological study was conducted via phone interview in December 2020 in Spain, with a representative sample from 17 autonomous communities. The study design was identical to that of the studies carried out in 2005 and 2011 to evaluate the changes that have occurred in seeking medical attention and performing spirometry in Spain, as well as the variability between autonomous communities. Results: From 89,601 phone contacts, a total of 6534 respondents were obtained. A total of 24.8% reported having some chronic respiratory symptom, and 17.9% reported a respiratory disease. Only 51.6% of those who had some chronic respiratory symptom had seen their doctor, which was less likely among current smokers (OR: 0.599, 95% CI: 0.467–0.769, p < 0.001) and those living in a rural setting (OR: 0.797, 95% CI: 0.651–0.975, p = 0.027). A total of 68.7% of the individuals who saw a doctor reported having undergone spirometry, most frequently males (OR: 1.535, 95% CI: 2.074–1.136, p < 0.005), former smokers (OR: 1.696, 95% CI: 2.407–1.195, p < 0.003), and those seen by a pulmonologist (OR: 6.151, 95% CI: 8.869–4.265, p < 0.001). With respect to the 2005 survey, more frequent use of spirometry has been observed (42.6 vs. 68.7%), without any change in seeking medical attention for respiratory symptoms. There is a clear variability according to the autonomous community (p < 0.05). Conclusions: Many individuals with chronic respiratory symptoms do not seek medical attention and although the use of spirometry has increased in the past 15 years, it is still an important area that needs improving in the primary care setting, especially among women. Both of these factors can be determinants in the underdiagnosis of COPD and its variability between autonomous communities.This study has been promoted and sponsored by the Spanish Society of Pneumology and Thoracic Surgery (SEPAR). We thank GlaxoSmithKline Spain for its financial support in carrying out the study; grant number 214465. The financing entities did not participate in the design of the study, data collection, analysis, publication, or preparation of this manuscript

Smoking and COPD Knowledge in the General Spanish Population: A CONOCEPOC Study

Chronic obstructive pulmonary disease; Knowledge; Tobacco useMalaltia pulmonar obstructiva crònica; Coneixement; Consum de tabacEnfermedad pulmonar obstructiva crónica; Conocimiento; Consumo de tabacoBackground: The objective of this analysis is to evaluate tobacco use and the level of chronic obstructive pulmonary disease (COPD) knowledge among the general adult population in Spain and to compare these results to those obtained in the 2011 survey. Methods: A cross-sectional, observational, epidemiological study was conducted by telephone interviews and stratified by sex, age, and setting. The study design was identical to that of the study conducted in 2011. Results: Of a total of 89,601 phone contacts, there were 6534 respondents. The average age was 61.5 years. With respect to smoking, 30.9% reported being former smokers and 14.7% were current smokers, 63.6% of whom reported having attempted to quit. Among the current smokers, 19.7% claimed to use electronic cigarettes, although 88% believe these pose a health risk. No significant differences were found in smoking prevalence or frequency of attempts to quit according to residential setting (rural/urban). The highest prevalence of current smoking in men was recorded in the 55–64 years age range (31.6%), while in women it was from 45 to 54 years (34.6%). Smoking has decreased with respect to 2011, from 21.1% to 16.1% in men and from 17.9% to 13.2% in women, with a clear variability according to region. Of the population surveyed, 32.5% had spontaneous knowledge about COPD, with significant geographic variability. The most frequent sources of information about the disease were social media and the Internet (39.6%), followed by the media (35.2%). Conclusions: The prevalence of tobacco use in adults has considerably decreased and there is greater knowledge about COPD in Spain, although there is significant variability according to region, which could explain the geographic variability in the prevalence of COPD. Strategies are needed to increase COPD education and awareness and to reinforce smoking prevention measures among women.This study has been promoted and sponsored by the Spanish Society of Pneumology and Thoracic Surgery (SEPAR). We thank GlaxoSmithKline Spain for its financial support in carrying out the study (grant number 214465). The financing entities did not participate in the design of the study, data collection, analysis, publication, or preparation of this manuscript

Integrating Comorbidities and Phenotype-Based Medicine in Patient-Centered Medicine in COPD

Despite recent notable innovations in the management of chronic obstructive pulmonary disease (COPD), no major advances in patient-centered medicine have been achieved. Current guidelines base their proposals on the average results from clinical trials, leading to what could be termed ‘means-based’ medical practice. However, the therapeutic response is variable at the patient level. Additionally, the variability of the clinical presentation interacts with comorbidities to form a complex clinical scenario for clinicians to deal with. Consequently, no consensus has been reached over a practical approach for combining comorbidities and disease presentation markers in the therapeutic algorithm. In this context, from the patients’ first visit, the clinician faces four major dilemmas: (1) establishing the correct diagnosis of COPD as opposed to other airway diseases, such as bronchial asthma; (2) deciding on the initial therapeutic approach based on the clinical characteristics of each case; (3) setting up a study strategy for non-responding patients; (4) pursuing a follow-up strategy with two well-defined periods according to whether close or long-term follow-up is required. Here, we will address these major dilemmas in the search for a patient-centered approach to COPD management and suggest how to combine them all in a single easy-to-use strategy

Testing for alpha-1 antitrypsin in COPD in outpatient respiratory clinics in Spain: A multilevel, cross-sectional analysis of the EPOCONSUL study

Background Alpha-1 antitrypsin deficiency (AATD) is the most common hereditary disorder in adults, but is under-recognized. In Spain, the number of patients diagnosed with AATD is much lower than expected according to epidemiologic studies. The objectives of this study were to assess the frequency and determinants of testing serum α1-antitrypsin (AAT) levels in COPD patients, and to describe factors associated with testing. Methods EPOCONSUL is a cross-sectional clinical audit, recruiting consecutive COPD cases over one year. The study evaluated serum AAT level determination in COPD patients and associations between individual, disease-related, and hospital characteristics. Results A total of 4,405 clinical records for COPD patients from 57 Spanish hospitals were evaluated. Only 995 (22.5%) patients had serum AAT tested on some occasion. A number of patient characteristics (being male [OR 0.5, p < 0.001], ≤55 years old [OR 2.38, p<0.001], BMI≤21 kg/m2 [OR 1.71, p<0.001], FEV1(%)<50% [OR 1.35, p<0.001], chronic bronchitis [OR 0.79, p < 0.001], Charlson index ≥ 3 [OR 0.66, p < 0.001], or history or symptoms of asthma [OR 1.32, p<0.001]), and management at a specialized COPD outpatient clinic [OR 2.73,p<0.001] were identified as factors independently associated with ever testing COPD patients for AATD. Overall, 114 COPD patients (11.5% of those tested) had AATD. Of them, 26 (22.8%) patients had severe deficiency. Patients with AATD were younger, with a low pack-year index, and were more likely to have emphysema (p<0.05). Conclusion Testing of AAT blood levels in COPD patients treated at outpatient respiratory clinics in Spain is infrequent. However, when tested, AATD (based on the serum AAT levels ≤100 mg/dL) is detected in one in five COPD patients. Efforts to optimize AATD case detection in COPD are needed.SEPA

The Expression of AQP1 IS Modified in Lung of Patients With Idiopathic Pulmonary Fibrosis: Addressing a Possible New Target

Activation of the epithelial-mesenchymal transition process (EMT) by which alveolar cells in human lung tissue undergo differentiation giving rise to a mesenchymal phenotype (fibroblast/miofibroblasts) has been well recognized as a key element in the origin of idiopathic pulmonary fibrosis (IPF). Here we analyzed expression of AQP1 in lung biopsies of patients diagnosed with IPF, and compared it to biopsies derived from patients with diverse lung pneumonies, such as hypersensitivity pneumonitis, sarcoidosis or normal lungs. Immunostaining for AQP1 showed a clear increment of AQP1 localized in the alveolar epithelium in biopsies from IPF patients alone. Moreover, to examine the possible participation of AQP1 in the pathophysiology of IPF, we evaluated its role in the pro-fibrotic transformation induced by transforming growth factor (TGF-β) in vitro. Human alveolar epithelial cells (A549), and fibroblasts derived from an IPF patient (LL29), or fibroblasts from healthy normal lung tissue (MRC-5), were treated with TGF-β, and levels of expression of AQP1, as well as those of E-cadherin, vimentin, α-SMA and collagen were analyzed by RT-qPCR, western blot and immunohistochemistry. An increase of AQP1 mRNA and protein after TGF-β treatment (4-72h) was observed either in A549 or IPF fibroblast-LL29 but not in MRC-5 fibroblasts. A gradual reduction of E-cadherin, and increased expression of vimentin, with no changes in α-SMA levels were observed in A549. Whereas in LL29 and MRC-5, TGF-β1 elicited a large production of collagen and α-SMA that was significantly greater in IPF fibroblast-LL29. Changes observed are consistent with activation of EMT by TGF-β, but whether modifications in AQP1 expression are responsible or independent events occurring at the same time is still unknown. Our results suggest that AQP1 plays a role in the pro-fibrotic TGF-β action and contributes to the etiology and pathophysiology of IPF. Understanding AQP1's role will help us comprehend the fate of this disease.Fondos FEDER (UE)Fundación NeumosurFundación SEPARISCIII Instituto de Salud Carlos II

Dysfunction in the Cystic Fibrosis Transmembrane Regulator in Chronic Obstructive Pulmonary Disease as a Potential Target for Personalised Medicine

In recent years, numerous pathways were explored in the pathogenesis of COPD in the quest for new potential therapeutic targets for more personalised medical care. In this context, the study of the cystic fibrosis transmembrane conductance regulator (CFTR) began to gain importance, especially since the advent of the new CFTR modulators which had the potential to correct this protein’s dysfunction in COPD. The CFTR is an ion transporter that regulates the hydration and viscosity of mucous secretions in the airway. Therefore, its abnormal function favours the accumulation of thicker and more viscous secretions, reduces the periciliary layer and mucociliary clearance, and produces inflammation in the airway, as a consequence of a bronchial infection by both bacteria and viruses. Identifying CFTR dysfunction in the context of COPD pathogenesis is key to fully understanding its role in the complex pathophysiology of COPD and the potential of the different therapeutic approaches proposed to overcome this dysfunction. In particular, the potential of the rehydration of mucus and the role of antioxidants and phosphodiesterase inhibitors should be discussed. Additionally, the modulatory drugs which enhance or restore decreased levels of the protein CFTR were recently described. In particular, two CFTR potentiators, ivacaftor and icenticaftor, were explored in COPD. The present review updated the pathophysiology of the complex role of CFTR in COPD and the therapeutic options which could be explored

Demographic and clinical characteristics of patients with α1-antitrypsin deficiency genotypes PI*ZZ and PI*SZ in the Spanish registry of EARCO

Spanish registry; Clinical characteristicsRegistre espanyol; Característiques clíniquesRegistro español; Características clínicasBackground The Spanish registry of α1-antitrypsin deficiency (AATD) integrated in the European Alpha-1 Research Collaboration (EARCO) provides information about the characteristics of patients, in particular those with the PI*SZ genotype, which is frequent in Spain. Method Individuals with severe AATD defined as proteinase inhibitor (PI) genotypes PI*ZZ, PI*SZ and other rare deficient variants were included from February 1, 2020, to February 1, 2022. The analysis focused on a comparison of the characteristics of PI*ZZ and PI*SZ patients. Results 409 patients were included (53.8% men) with a mean±sd age of 53.5±15.9 years. Genotypes were PI*ZZ in 181 (44.7%), PI*SZ in 163 (40.2%), PI*SS in 29 (7.2%) and other in 32 (7.9%). 271 (67.4%) had lung disease: 175 chronic obstructive pulmonary disease (43.5%), 163 emphysema (40.5%) and 83 bronchiectasis (20.6%). Patients with the PI*SZ genotype were younger, more frequently non-index cases and had a lower frequency of respiratory diseases except asthma compared with PI*ZZ patients. Among patients with respiratory diseases, PI*SZ individuals were significantly older both at onset of symptoms and at diagnosis; only asthma was more frequent in PI*SZ than in PI*ZZ individuals. Twelve PI*SZ patients (15.4%) received augmentation therapy compared with 94 PI*ZZ patients (66.2%; p<0.001). Conclusions There is a high prevalence of PI*SZ in Spain. Patients with the PI*SZ genotype were older at symptom onset and diagnosis and had less severe lung disease compared with PI*ZZ patients. The prevalence of asthma was higher in PI*SZ, and up to 15% of PI*SZ patients received augmentation therapy

Clinical and functional characteristics of individuals with alpha-1 antitrypsin deficiency: EARCO international registry

Background Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history. Methods The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels < 11 μM and/or proteinase inhibitor genotypes PI*ZZ, PI*SZ and compound heterozygotes or homozygotes of other rare deficient variants. We describe the characteristics of the individuals included from February 2020 to May 2022. Results A total of 1044 individuals from 15 countries were analysed. The most frequent genotype was PI*ZZ (60.2%), followed by PI*SZ (29.2%). Among PI*ZZ patients, emphysema was the most frequent lung disease (57.2%) followed by COPD (57.2%) and bronchiectasis (22%). Up to 76.4% had concordant values of FEV1(%) and KCO(%). Those with impairment in FEV1(%) alone had more frequently bronchiectasis and asthma and those with impairment in KCO(%) alone had more frequent emphysema and liver disease. Multivariate analysis showed that advanced age, male sex, exacerbations, increased blood platelets and neutrophils, augmentation and lower AAT serum levels were associated with worse FEV1(%). Conclusions EARCO has recruited > 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function

Clinical and functional characteristics of individuals with alpha-1 antitrypsin deficiency: EARCO international registry

Alpha-1 antitrypsin; Phenotypes; RegistryAlfa-1 antitripsina; Fenotipos; RegistroAlfa-1 antitripsina; Fenotips; RegistreBackground Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history. Methods The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels < 11 μM and/or proteinase inhibitor genotypes PI*ZZ, PI*SZ and compound heterozygotes or homozygotes of other rare deficient variants. We describe the characteristics of the individuals included from February 2020 to May 2022. Results A total of 1044 individuals from 15 countries were analysed. The most frequent genotype was PI*ZZ (60.2%), followed by PI*SZ (29.2%). Among PI*ZZ patients, emphysema was the most frequent lung disease (57.2%) followed by COPD (57.2%) and bronchiectasis (22%). Up to 76.4% had concordant values of FEV1(%) and KCO(%). Those with impairment in FEV1(%) alone had more frequently bronchiectasis and asthma and those with impairment in KCO(%) alone had more frequent emphysema and liver disease. Multivariate analysis showed that advanced age, male sex, exacerbations, increased blood platelets and neutrophils, augmentation and lower AAT serum levels were associated with worse FEV1(%). Conclusions EARCO has recruited > 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function.The International EARCO registry is funded by unrestricted grants of Grifols, CSL Behring, Kamada, pH Pharma and Takeda to the European Respiratory Society (ERS)