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BACKGROUND: Sex and gender influence many aspects of chronic obstructive pulmonary disease (COPD). Limited data are available on this topic in alpha-1 antitrypsin deficiency (AATD). We therefore aimed to investigate sex issues in the EARCO registry, a prospective, international, observational cohort study. METHODS: Baseline data from PiZZ individuals, enrolled in the registry with complete data on sex and smoking history were analysed by group comparisons and binary logistic regression analyses. RESULTS: 1283 patients with AATD, 49.3% women were analysed. Females reported less tobacco consumption (16.8±12.2 vs. 19.6±14.5 PY, p=0.006), occupational exposures towards gases, dusts or asbestos (p<0.005 each) and consumed less alcohol (5.5±7.6 vs. 8.4±10.3u/week, p<0.001). Females reported COPD (41% vs. 57%, p<0.001) and liver disease (11% vs. 20%, p<0.001) less often. However, they had a higher prevalence of bronchiectasis (24% vs. 13%, p<0.001). Despite better lung function (FEV1%pred. 73.6±29.9 vs. 62.7±29.5, p<0.001) females reported a similar symptom burden (CAT 13.4±9.5 vs. 12.5±8.9, p=ns) and exacerbation frequency (at least one in the previous year 30% vs. 26%, p=ns) compared to males. In multivariate analyses, female sex was an independent risk factor for exacerbations in the previous year OR 1.6 p=0.001 in addition to smoking history, COPD, asthma and bronchiectasis and was also identified as risk factors for symptom burden (CAT≥10) OR 1.4 p=0.014 besides age, BMI, COPD and smoking history. CONCLUSION: Men had higher rates of COPD and liver disease, women were more likely to have bronchiectasis. Women's higher symptom burden and exacerbation frequency suggest they may need tailored treatment approaches.
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BACKGROUND: The PI*S variant is one of the most prevalent mutations within alpha-1 antitrypsin deficiency (AATD). The risk of developing AATD-related lung disease in individuals with the PI*SS genotype is poorly defined despite its substantial prevalence. Our study aimed to characterize this genotype and its risk for lung disease and compare it with the PI*ZZ and PI*SZ genotypes using data from the European Alpha-1 antitrypsin Deficiency Research Collaboration international registry. METHOD: Demographic, clinical, functional, and quality of life (QoL) parameters were assessed to compare the PI*SS characteristics with the PI*SZ and PI*ZZ controls. A propensity score with 1:3 nearest-neighbour matching was performed for the most important confounding variables. RESULTS: The study included 1007 individuals, with PI*SS (n = 56; 5.6%), PI*ZZ (n = 578; 57.4%) and PI*SZ (n = 373; 37.0%). The PI*SS population consisted of 58.9% men, with a mean age of 59.2 years and a mean FEV1(% predicted) of 83.4%. Compared to PI*ZZ individuals they had less frequent lung disease (71.4% vs. 82.2%, p = 0.037), COPD (41.4% vs. 60%, p = 0.002), and emphysema (23.2% vs. 51.9%, p < 0.001) and better preserved lung function, fewer exacerbations, lower level of dyspnoea, and better QoL. In contrast, no significant differences were found in the prevalence of lung diseases between PI*SS and PI*SZ, or lung function parameters, exacerbations, dyspnoea, or QoL. CONCLUSIONS: We found that, as expected, the risk of lung disease associated with the PI*SS genotype is significantly lower compared with PI*ZZ, but does not differ from that observed in PI*SZ individuals, despite having higher serum AAT levels. TRIAL REGISTRATION: www. CLINICALTRIALS: gov (ID: NCT04180319).
Sujet(s)
Génotype , Déficit en alpha-1-antitrypsine , alpha-1-Antitrypsine , Humains , Mâle , Femelle , Adulte d'âge moyen , alpha-1-Antitrypsine/génétique , Déficit en alpha-1-antitrypsine/génétique , Déficit en alpha-1-antitrypsine/épidémiologie , Déficit en alpha-1-antitrypsine/diagnostic , Sujet âgé , Maladies pulmonaires/génétique , Maladies pulmonaires/épidémiologie , Maladies pulmonaires/diagnostic , Facteurs de risque , Enregistrements , Qualité de vieRÉSUMÉ
Long COVID is a condition that affects a significant proportion of patients who have had COVID-19. It is characterised by the persistence of associated symptoms after the acute phase of the illness has subsided. Although several studies have investigated the risk factors associated with long COVID, identifying which patients will experience long-term symptoms remains a complex task. Among the various symptoms, dyspnea is one of the most prominent due to its close association with the respiratory nature of COVID-19 and its disabling consequences. This work proposes a new intelligent clinical decision support system to predict dyspnea 12 months after a severe episode of COVID-19 based on the SeguiCovid database from the Álvaro Cunqueiro Hospital in Vigo (Galicia, Spain). The database is initially processed using a CART-type decision tree to identify the variables with the highest predictive power. Based on these variables, a cascade of expert systems has been defined with Mamdani-type fuzzy-inference engines. The rules for each system were generated using the Wang-Mendel automatic rule generation algorithm. At the output of the cascade, a risk indicator is obtained, which allows for the categorisation of patients into two groups: those with dyspnea and those without dyspnea at 12 months. This simplifies follow-up and the performance of studies aimed at those patients at risk. The system has produced satisfactory results in initial tests, supported by an AUC of 0.75, demonstrating the potential and usefulness of this tool in clinical practice.
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Purpose: Administration of exogenous alpha-1 antitrypsin (AAT) is the only specific therapy for the management of pulmonary morbidity in patients with AAT deficiency. It requires weekly or biweekly intravenous infusions, which may impact patient independence and quality of life. Self-administration of AAT therapy is an alternative to reduce the burden for patients who require AAT therapy. We presented herein experts' recommendations for the implementation of a program for the self-administration of AAT. Methods: This project was conducted using a modified nominal group technique and was undertaken in two online meetings involving the participation of 25 experts: specialists in pulmonology (n=17), nurses (n=5) and hospital pharmacists (n=3). Results: The following issues were discussed, and several recommendations were agreed upon on the following topics: a) patient profile and clinical evaluation, establishing selection criteria that should include clinical as well as social criteria; b) role of health care professionals, suggested roles for specialists in pulmonology, nurses, and hospital pharmacists; c) training by the nurse, including recommendations before initiating the training and the content of the training sessions; and d) logistic issues and follow-up, adherence, and patient support. Conclusion: We expect this proposal to increase awareness of this therapeutic alternative and facilitate the implementation of self-administration programs, thus contributing to optimizing the patient experience with AAT therapy. Further research on the outcomes of these programs, especially from the patient perspective, will also help to improve their design and implementation.
Sujet(s)
Broncho-pneumopathie chronique obstructive , Déficit en alpha-1-antitrypsine , Humains , Qualité de vie , Broncho-pneumopathie chronique obstructive/traitement médicamenteux , alpha-1-Antitrypsine/usage thérapeutique , Déficit en alpha-1-antitrypsine/diagnostic , Déficit en alpha-1-antitrypsine/traitement médicamenteux , Perfusions veineusesRÉSUMÉ
Obstructive sleep apnea (OSA), characterized by recurrent episodes of partial or total obstruction of the upper airway during sleep, is currently one of the respiratory pathologies with the highest incidence worldwide. This situation has led to an increase in the demand for medical appointments and specific diagnostic studies, resulting in long waiting lists, with all the health consequences that this entails for the affected patients. In this context, this paper proposes the design and development of a novel intelligent decision support system applied to the diagnosis of OSA, aiming to identify patients suspected of suffering from the pathology. For this purpose, two sets of heterogeneous information are considered. The first one includes objective data related to the patient's health profile, with information usually available in electronic health records (anthropometric information, habits, diagnosed conditions and prescribed treatments). The second type includes subjective data related to the specific OSA symptomatology reported by the patient in a specific interview. For the processing of this information, a machine-learning classification algorithm and a set of fuzzy expert systems arranged in cascade are used, obtaining, as a result, two indicators related to the risk of suffering from the disease. Subsequently, by interpreting both risk indicators, it will be possible to determine the severity of the patients' condition and to generate alerts. For the initial tests, a software artifact was built using a dataset with 4400 patients from the Álvaro Cunqueiro Hospital (Vigo, Galicia, Spain). The preliminary results obtained are promising and demonstrate the potential usefulness of this type of tool in the diagnosis of OSA.
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Small cell lung cancer (SCLC) comprises approximately 10% of all lung cancer cases. Tobacco is its main risk factor; however, occupation might play a role in this specific lung cancer subtype. The effect of occupation on SCLC risk has been hardly studied and therefore we aim to assess the role of occupation on the risk of SCLC. To do this, we designed a multicentric, hospital-based, case-control study. Cases consisted exclusively in SCLC patients and controls were recruited from patients having minor surgery at the participating hospitals. Face to face interviews emphasizing occupation and tobacco consumption were held and residential radon was also measured. Logistic regression models were adjusted with odds ratios with 95%CI as estimations of the effect. 423 cases and 905 controls were included. Smoking prevalence was higher in cases compared to controls. Those who worked in known-risk occupations for lung cancer showed an OR of 2.17 (95%CI 1.33; 3.52), with a similar risk when men were analysed separately. The results were adjusted by age, sex, smoking and indoor radon exposure. Those who worked in known-risk occupations and were moderate or heavy smokers had a SCLC risk of 12.19 (95%CI 5.68-26.38) compared with never or moderate smokers who had not worked in such occupations. Occupation is a relevant risk factor of SCLC, and it seems that its effect is boosted when tobacco smoking is present.
Sujet(s)
Tumeurs du poumon , Radon , Carcinome pulmonaire à petites cellules , Mâle , Humains , Carcinome pulmonaire à petites cellules/étiologie , Carcinome pulmonaire à petites cellules/complications , Études cas-témoins , Tumeurs du poumon/épidémiologie , Tumeurs du poumon/étiologie , Facteurs de risque , Radon/effets indésirables , Radon/analyse , ProfessionsRÉSUMÉ
BACKGROUND: Epidemiologic studies have reported that the geographical distribution of the prevalence of allelic variants of serine protein inhibitor-A1 (SERPINA1) and severe cases of COVID-19 were similar. METHODS: A multicenter, cross-sectional, observational study to evaluate the frequency of alpha-1 antitrypsin deficiency (AATD) in patients with COVID-19 and whether it was associated with having suffered severe COVID-19. RESULTS: 2022 patients who had laboratory-confirmed SARS-CoV-2 infection. Mutations associated with AATD were more frequent in severe COVID versus non-severe (23% vs. 18.8%, p = 0.022). The frequency of Pi*Z was 37.8/1000 in severe COVID versus 17.5/1000 in non-severe, p = 0.001. Having an A1AT level below 116 was more frequent in severe COVID versus non-severe (29.5% vs. 23.1, p = 0.003). Factors associated with a higher likelihood of severe COVID-19 were being male, older, smoking, age-associated comorbidities, and having an A1AT level below 116 mg/dL [OR 1.398, p = 0.003], and a variant of the SERPINA1 gene that could affect A1AT protein [OR 1.294, p = 0.022]. CONCLUSIONS: These observations suggest that patients with AATD should be considered at a higher risk of developing severe COVID-19. Further studies are needed on the role of A1AT in the prognosis of SARS-CoV-2 infection and its possible therapeutic role.
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Obstructive Sleep Apnea (OSA) is a chronic sleep-related pathology characterized by recurrent episodes of total or partial obstruction of the upper airways during sleep. It entails a high impact on the health and quality of life of patients, affecting more than one thousand million people worldwide, which has resulted in an important public health concern in recent years. The usual diagnosis involves performing a sleep test, cardiorespiratory polygraphy, or polysomnography, which allows characterizing the pathology and assessing its severity. However, this procedure cannot be used on a massive scale in general screening studies of the population because of its execution and implementation costs; therefore, causing an increase in waiting lists which would negatively affect the health of the affected patients. Additionally, the symptoms shown by these patients are often unspecific, as well as appealing to the general population (excessive somnolence, snoring, etc.), causing many potential cases to be referred for a sleep study when in reality are not suffering from OSA. This paper proposes a novel intelligent clinical decision support system to be applied to the diagnosis of OSA that can be used in early outpatient stages, quickly, easily, and safely, when a suspicious OSA patient attends the consultation. Starting from information related to the patient's health profile (anthropometric data, habits, comorbidities, or medications taken), the system is capable of determining different alert levels of suffering from sleep apnea associated with different apnea-hypopnea index (AHI) levels to be studied. To that end, a series of automatic learning algorithms are deployed that, working concurrently, together with a corrective approach based on the use of an Adaptive Neuro-Based Fuzzy Inference System (ANFIS) and a specific heuristic algorithm, allow the calculation of a series of labels associated with the different levels of AHI previously indicated. For the initial software implementation, a data set with 4600 patients from the Álvaro Cunqueiro Hospital in Vigo was used. The results obtained after performing the proof tests determined ROC curves with AUC values in the range 0.8-0.9, and Matthews correlation coefficient values close to 0.6, with high success rates. This points to its potential use as a support tool for the diagnostic process, not only from the point of view of improving the quality of the services provided, but also from the best use of hospital resources and the consequent savings in terms of costs and time.
Sujet(s)
Systèmes d'aide à la décision clinique , Syndromes d'apnées du sommeil , Syndrome d'apnées obstructives du sommeil , Humains , Qualité de vie , Syndrome d'apnées obstructives du sommeil/épidémiologie , RonflementRÉSUMÉ
BACKGROUND: Patients with alpha-1 antitrypsin deficiency (AATD), commonly categorized as a rare disease, have been affected by the changes in healthcare management brought about by COVID-19. This study's aim was to identify the changes that have taken place in AATD patient care as a result of the COVID-19 pandemic in Spain and to propose experts' recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation. METHODS: A qualitative descriptive case study with a holistic single-case design was conducted, using focus groups with experts in AATD clinical management, including 15 health professionals with ties to the Spanish health system (12 pneumologists and 2 hospital pharmacists from 11 different hospitals in Spain) and 1 patient representative. RESULTS: COVID-19 has had a major impact on numerous aspects of AATD clinical patient management in Spain, including diagnostic, treatment, and follow-up phases. The experts concluded that there is a need to strengthen coordination between Primary Care and Hospital Care and improve the coordination processes across all the organizations and actors involved in the healthcare system. Regarding telemedicine and telecare, experts have concluded that it is necessary to promote this methodology and to develop protocols and training programs. Experts have recommended developing personalized and precision medicine, and patient participation in decision-making, promoting self-care and patient autonomy to optimize their healthcare and improve their quality of life. The possibility of monitoring and treating AATD patients from home has also been proposed by experts. Another result of the study was the recommendation of the need to ensure that plasma donations are made on a regular basis by a sufficient number of healthy individuals. CONCLUSION: The study advances knowledge by highlighting the challenges faced by health professionals and changes in AATD patient management in the context of the COVID-19 pandemic. It also proposes experts' recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation. This work could serve as a reference study for physicians on their daily clinical practice with AATD patients and may also provide guidance on the changes to be put in place for the post-pandemic situation.
Sujet(s)
COVID-19 , Broncho-pneumopathie chronique obstructive , Déficit en alpha-1-antitrypsine , Humains , Pandémies , Qualité de vie , COVID-19/épidémiologie , Déficit en alpha-1-antitrypsine/diagnostic , Déficit en alpha-1-antitrypsine/traitement médicamenteux , Prestations des soins de santé , Broncho-pneumopathie chronique obstructive/thérapieRÉSUMÉ
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. Trial registration www. CLINICALTRIALS: gov (ID: NCT04180319).
Sujet(s)
Dilatation des bronches , Broncho-pneumopathie chronique obstructive , Emphysème pulmonaire , Déficit en alpha-1-antitrypsine , Humains , Mâle , alpha-1-Antitrypsine/génétique , Déficit en alpha-1-antitrypsine/diagnostic , Déficit en alpha-1-antitrypsine/épidémiologie , Déficit en alpha-1-antitrypsine/génétique , Dilatation des bronches/diagnostic , Dilatation des bronches/épidémiologie , Études transversales , Génotype , Études prospectives , Broncho-pneumopathie chronique obstructive/génétique , Emphysème pulmonaire/diagnostic , Emphysème pulmonaire/épidémiologie , Emphysème pulmonaire/complications , EnregistrementsRÉSUMÉ
Background: 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±15.9â 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.
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Introduction: Residential radon is considered the second cause of lung cancer and the first in never smokers. Nevertheless, there is little information regarding the association between elevated radon levels and small cell lung cancer (SCLC). We aimed to assess the effect of residential radon exposure on the risk of SCLC in general population through a multicentric casecontrol study. Methods: A multicentric hospital-based casecontrol study was designed including 9 hospitals from Spain and Portugal, mostly including radon-prone areas. Indoor radon was measured using Solid State Nuclear Track Detectors at the Galician Radon Laboratory. Results: A total of 375 cases and 902 controls were included, with 24.5% of cases being women. The median number of years living in the measured dwelling was higher than 25 years for both cases and controls. There was a statistically significant association for those exposed to concentrations higher than the EPA action level of 148Bq/m3, with an Odds Ratio of 2.08 (95%CI: 1.034.39) compared to those exposed to concentrations lower than 50Bq/m3. When using a dose-response model with 100Bq/m3 as a reference, it can be observed a linear effect for small cell lung cancer risk. Smokers exposed to higher radon concentrations pose a much higher risk of SCLC compared to smokers exposed to lower indoor radon concentrations. Conclusions: Radon exposure seems to increase the risk of small cell lung cancer with a linear dose-response pattern. Tobacco consumption may also produce an important effect modification for radon exposure. (AU)
Sujet(s)
Humains , Adulte , Adulte d'âge moyen , Sujet âgé , Sujet âgé de 80 ans ou plus , Radon , Tumeurs du poumon , Nicotiana , Espagne , Portugal , FumeursRÉSUMÉ
Introduction: Tobacco consumption and radon exposure are considered the first and second most common causes of lung cancer, respectively. The aim of this study was to analyze both whether selected genetic polymorphisms in loci that are in DNA repair pathways, are related to non-small-cell lung cancer (NSCLC) and whether they may modulate the association between residential radon exposure and lung cancer in both smokers and never smokers.Methods: A multicentre, hospital-based, casecontrol study with 826 cases and 1201 controls was designed in a radon-prone area. Genotyping was determined in whole blood and residential radon exposure was measured in participants dwellings.Results: Attending to tobacco exposure, the variant in the gene NBN (rs1805794) was associated with lung cancer in never smokers (OR 2.72; 95%1.445.2) and heavy smokers (OR 3.04; 95%CI 1.217.69). The polymorphism with the highest lung cancer association was OGG1 (rs125701), showing an OR of 8.04 (95%CI 1.6458.29) for its homozygous variant genotype in heavy smokers. Attending to indoor radon exposure (>200Bq/m3), rs1452584, for its homozygous variant genotype, showed the highest association (OR 3.04 (95%CI 1.158.48).Conclusion: The genes analyzed seem to have no association with the fully adjusted model, but they might modulate lung cancer association when different categories of tobacco consumption are considered (i.e. heavy smokers). This association may similarly be elevated for those individuals having high indoor radon exposures, though at a minor extent. (AU)
Introducción: El consumo de tabaco y la exposición al radón se consideran la primera y la segunda causa más frecuentes de cáncer de pulmón, respectivamente. El objetivo de este estudio fue analizar si determinados polimorfismos genéticos en los loci que forman parte de la cascada de reparación del ADN se asocian con el cáncer de pulmón de célula no pequeña, y también si es posible que modifiquen la asociación entre la exposición al radón en el hogar y el cáncer de pulmón tanto en fumadores como en no fumadores.Métodos: Se diseñó un estudio multicéntrico hospitalario de casos y controles con 826 casos y 1.201 controles en un área proclive a la presencia de radón. Se determinó el genotipo en sangre y se midió la exposición al radón en el lugar de residencia de los participantes.Resultados: Analizando la exposición al tabaco, la variante del gen NBN (rs1805794) se asoció con el cáncer de pulmón en no fumadores (OR 2,72; IC 95% 1,44-5,2) y grandes fumadores (OR 3,04; IC 95% 1,21-7,69). El polimorfismo con mayor asociación con el cáncer de pulmón fue OGG1 (rs125701), con una OR de 8,04 (IC 95% 1,64-58,29) para la variante genotípica en homocigosis en grandes fumadores. En cuanto a la exposición al radón en interiores (>200Bq/m3), rs1452584 en homocigosis mostró la asociación más fuerte (OR 3,04; IC 95% 1,15-8,48).Conclusión: Los genes que se analizaron no muestran asociación con el modelo completamente ajustado, pero podrían modificar la asociación con el cáncer de pulmón cuando se consideran diferentes categorías de consumo de tabaco (esto es, grandes fumadores). Esta asociación podría aumentar de forma similar en aquellos individuos que están expuestos al radón en interiores, aunque en menor medida. (AU)
Sujet(s)
Humains , Pollution par la fumée de tabac , Radon , Tumeurs du poumon , Non-fumeurs , GènesRÉSUMÉ
INTRODUCTION: Residential radon is considered the second cause of lung cancer and the first in never smokers. Nevertheless, there is little information regarding the association between elevated radon levels and small cell lung cancer (SCLC). We aimed to assess the effect of residential radon exposure on the risk of SCLC in general population through a multicentric case-control study. METHODS: A multicentric hospital-based case-control study was designed including 9 hospitals from Spain and Portugal, mostly including radon-prone areas. Indoor radon was measured using Solid State Nuclear Track Detectors at the Galician Radon Laboratory. RESULTS: A total of 375 cases and 902 controls were included, with 24.5% of cases being women. The median number of years living in the measured dwelling was higher than 25 years for both cases and controls. There was a statistically significant association for those exposed to concentrations higher than the EPA action level of 148Bq/m3, with an Odds Ratio of 2.08 (95%CI: 1.03-4.39) compared to those exposed to concentrations lower than 50Bq/m3. When using a dose-response model with 100Bq/m3 as a reference, it can be observed a linear effect for small cell lung cancer risk. Smokers exposed to higher radon concentrations pose a much higher risk of SCLC compared to smokers exposed to lower indoor radon concentrations. CONCLUSIONS: Radon exposure seems to increase the risk of small cell lung cancer with a linear dose-response pattern. Tobacco consumption may also produce an important effect modification for radon exposure.
Sujet(s)
Pollution de l'air intérieur , Tumeurs du poumon , Tumeurs radio-induites , Radon , Carcinome pulmonaire à petites cellules , Pollution de l'air intérieur/effets indésirables , Études cas-témoins , Exposition environnementale/effets indésirables , Femelle , Logement , Humains , Tumeurs du poumon/épidémiologie , Tumeurs du poumon/étiologie , Mâle , Tumeurs radio-induites/épidémiologie , Tumeurs radio-induites/étiologie , Radon/toxicité , Facteurs de risque , Carcinome pulmonaire à petites cellules/épidémiologie , Carcinome pulmonaire à petites cellules/étiologieRÉSUMÉ
INTRODUCTION: Tobacco consumption and radon exposure are considered the first and second most common causes of lung cancer, respectively. The aim of this study was to analyze both whether selected genetic polymorphisms in loci that are in DNA repair pathways, are related to non-small-cell lung cancer (NSCLC) and whether they may modulate the association between residential radon exposure and lung cancer in both smokers and never smokers. METHODS: A multicentre, hospital-based, case-control study with 826 cases and 1201 controls was designed in a radon-prone area. Genotyping was determined in whole blood and residential radon exposure was measured in participants' dwellings. RESULTS: Attending to tobacco exposure, the variant in the gene NBN (rs1805794) was associated with lung cancer in never smokers (OR 2.72; 95%1.44-5.2) and heavy smokers (OR 3.04; 95%CI 1.21-7.69). The polymorphism with the highest lung cancer association was OGG1 (rs125701), showing an OR of 8.04 (95%CI 1.64-58.29) for its homozygous variant genotype in heavy smokers. Attending to indoor radon exposure (>200Bq/m3), rs1452584, for its homozygous variant genotype, showed the highest association (OR 3.04 (95%CI 1.15-8.48). CONCLUSION: The genes analyzed seem to have no association with the fully adjusted model, but they might modulate lung cancer association when different categories of tobacco consumption are considered (i.e. heavy smokers). This association may similarly be elevated for those individuals having high indoor radon exposures, though at a minor extent.
Sujet(s)
Pollution de l'air intérieur , Carcinome pulmonaire non à petites cellules , Tumeurs du poumon , Tumeurs radio-induites , Radon , Pollution de l'air intérieur/effets indésirables , Carcinome pulmonaire non à petites cellules/étiologie , Carcinome pulmonaire non à petites cellules/génétique , Études cas-témoins , Humains , Tumeurs du poumon/étiologie , Tumeurs du poumon/génétique , Tumeurs radio-induites/étiologie , Polymorphisme génétique , Radon/effets indésirables , Facteurs de risque , NicotianaRÉSUMÉ
BACKGROUND: Augmentation therapy (AT) is the only specific treatment licensed for patients with alpha-1 antitrypsin deficiency (AATD) associated lung disease. Since patients with severe AATD may have a very different prognosis and AT requires intravenous infusions for life, the decision to initiate AT may be challenging. METHODS: This survey was conducted on 63 experts in AATD from 13 European countries about their opinions and attitudes regarding AT. Participants were asked to rank the importance of 11 identified factors related with the prescription of AT. In addition, each participant was asked to respond to the indication of AT for 30 out of 500 hypothetical cases developed with the combinations of the 11 factors. Each case was evaluated by 3 experts to check the concordance. RESULTS: The variables that scored higher on preferences for initiating AT were AAT genotype (score 8.6 from a Likert scale 0-10 (SD: 1.7)), AATD serum level (8.2 (SD:2.4)) and FEV1 (%) decline (7.9 (SD:2.4)). Among the 500 different cases, there was an agreement in indication of AT among the 3 experts in 291 (58.2%). Regarding the variables associated with AT, it was indicated to 81.9% of Pi*ZZ, 52.4% of Pi*SZ and 9.8% of Pi*MZ (p < 0.0001). For Pi*ZZ patients, multivariate analysis identified younger age, reduced FEV1 (%), higher FEV1 decline and worse emphysema as significantly associated with prescription (AUC = 0.8114); for Pi*SZ variables were younger age, worse FEV1 (%) and worse emphysema (AUC = 0.7414); and for Pi*MZ younger age, worse DLCO (%), higher DLCO decline and dyspnea (AUC = 0.8387). CONCLUSION: There is a high variability in the criteria for prescription of AT among European experts. Most cases were recommended AT according to guidelines, but a significant number of patients with genotype Pi*SZ and almost 10% Pi*MZ were recommended to initiate AT despite the lack of evidence of efficacy in these genotypes.
Sujet(s)
Broncho-pneumopathie chronique obstructive , Emphysème pulmonaire , Déficit en alpha-1-antitrypsine , Attitude , Humains , Broncho-pneumopathie chronique obstructive/complications , Broncho-pneumopathie chronique obstructive/diagnostic , Broncho-pneumopathie chronique obstructive/traitement médicamenteux , Emphysème pulmonaire/complications , Pneumologues , alpha-1-Antitrypsine/effets indésirables , alpha-1-Antitrypsine/génétique , Déficit en alpha-1-antitrypsine/complications , Déficit en alpha-1-antitrypsine/diagnostic , Déficit en alpha-1-antitrypsine/traitement médicamenteuxRÉSUMÉ
BACKGROUND: Lung cancer (LC) is the most commonly diagnosed cancer and the leading cause of cancer-related death in both sexes worldwide. Although the principal risk factor in the western world is tobacco smoking, genetic factors, including alpha-1 antitrypsin deficiency (AATD), have been associated with increased risk. This study is the continuation of an earlier one published by the same group in 2015, aimed at analysing risk of LC in never-smokers, associated with carriers of the AATD genotype. METHODS: A multicentre case-control study was conducted in Spain across the period January 2011 to August 2019. Cases were non-smokers diagnosed with LC, and controls were composed of never-smoking individuals undergoing major non-cancer-related surgery. Data were collected on epidemiological characteristics, exposure to environmental tobacco smoke (ETS), residential radon levels, and alpha-1 antitrypsin (AAT) genotype. RESULTS: The study included 457 cases (42%) and 631 controls (58%), with a predominance of women (72,8%). The most frequent histological type was adenocarcinoma (77.5%), followed by squamous cell carcinoma (7.7%). No association of risk of LC was found with the status of AATD genotype carrier, both overall and broken down by age, sex, or exposure to ETS. CONCLUSIONS: No risk association was found between being a carrier of an AAT deficiency genotype and LC among never-smokers. In order to establish the existence of an association, we consider it important to expand the studies in never smokers in different geographical areas as well as to include patients with previous chronic lung diseases to assess if it influences the risk.
Sujet(s)
Adénocarcinome/génétique , Carcinome épidermoïde/génétique , Prédisposition génétique à une maladie/épidémiologie , Tumeurs du poumon/génétique , Déficit en alpha-1-antitrypsine/génétique , Sujet âgé , Marqueurs biologiques tumoraux/génétique , Études cas-témoins , Femelle , Prédisposition génétique à une maladie/génétique , Génotype , Humains , Mâle , Adulte d'âge moyen , Facteurs de risque , Espagne/épidémiologie , alpha-1-Antitrypsine/génétiqueRÉSUMÉ
It is not known whether residential radon exposure may be linked to the development of chronic obstructive pulmonary disease (COPD) and/or have an influence on the functional characteristics or exacerbations of COPD. The aim of this study was therefore to ascertain whether there might be an association between residential radon concentrations and certain characteristics of COPD. We analyzed COPD cases drawn from a case-control study conducted in an area of high radon exposure. Data were collected on spirometric pulmonary function variables, hospital admissions, and smoking. Radon measurements were taken using alpha-track-type CR-39 detectors individually placed in patients' homes. All statistical analyses were performed using the IBM SPSS v22 computer software program. The study included 189 COPD cases (79.4% men; median age 64 years). The median radon concentration was 157 Bq/m3. No differences were found between radon concentration and sex, age or severity of breathing obstruction as measured by FEV1%. It should be noted, however, that 48.1% of patients with FEV1% < 50 had radon concentrations below 100 Bq/m3, as compared to 35.6% with the same severity of obstruction who had over 300 Bq/m3. COPD cases with radon concentrations higher than > 600 Bq/m3 exhibited no different characteristics in lung function. Exposure to radon does not appear to have an influence on the clinical characteristics of smokers and ex-smokers with COPD. As exposure to residential radon increases, there is no trend towards a worsening of FEV1%. Further studies are thus needed to analyze this possible association in never-smokers with COPD.