Risk of lung disease in the PI*SS genotype of alpha-1 antitrypsin: an EARCO research project.

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).

COVID-19's impact on care practice for alpha-1-antitrypsin deficiency patients.

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.

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. Trial registration www. CLINICALTRIALS: gov (ID: NCT04180319).

Alpha-1 antitrypsin deficiency and risk of lung cancer in never-smokers: a multicentre case-control study.

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.

Fruits and Vegetables and Lung Cancer Risk in Never Smokers. A Multicentric and Pooled Case-Control Study.

BACKGROUND: The etiology of lung cancer in never smokers is partly unknown. We aimed to assess the effect of fruits and vegetables consumption on lung cancer risk in never smokers. METHODS: We pooled five multicenter case-control studies performed in Northwestern Spain. Cases and controls were all never smokers. All lung cancer cases had anatomopathological confirmed diagnoses. We performed a multivariate logistic regression to analyze the effect of different types of fruits and vegetables consumption on lung cancer risk. RESULTS: A total of 438 cases and 781 controls were included. We observed that a consumption from one to six times per week shows a negative association with lung cancer risk for: kiwis (OR 0.67; 95%CI 0.46-0.95), oranges (OR 0.55; 95%CI 0.37-0.80), turnip tops (OR 0.48; 95%CI 0.34-0.66), "berza gallega" (OR 0.70; 95%CI 0.51-0.97) and broccoli (OR 0.55; 95%CI 0.35-0.83) compared to less than once a week consumption. On the other hand, we found an increased risk for lung cancer with a daily consumption of tomatoes, carrots and potatoes. CONCLUSIONS: Oranges, kiwis, turnip tops, berza gallega and broccoli may play a protective role on lung cancer development in never smokers while tomatoes, carrots and potatoes might have some association with this disease.

New cis-Acting Variants in PI*S Background Produce Null Phenotypes Causing Alpha-1 Antitrypsin Deficiency.

Alpha-1 antitrypsin deficiency (AATD) is an inherited condition characterized by reduced levels of serum AAT due to mutations in the SERPINA1 (Serpin family A member 1) gene. The Pi*S (Glu264Val) is one of the most frequent deficient alleles of AATD, showing high incidence in the Iberian Peninsula. Herein, we describe two new alleles carrying an S mutation but producing a null phenotype: QOVigo and QOAachen. The new alleles were identified by sequencing the SERPINA1 gene in three patients who had lower AAT serum levels than expected for the initial genotype. These alleles are the result of combined mutations in cis in a PI*S allele. Sequencing detected the S mutation in cis with Tyr138Cys (S+Tyr138Cys) in two patients, whereas a third one had the S mutation in cis with Pro391Thr variant (S+Pro391Thr). When expressed in a cellular model, these variants caused strong AAT polymerization and very low AAT secretion to almost undetectable levels. The isoelectric focusing method for plasma AAT phenotyping did not show AAT protein encoded by the novel mutant alleles, behaving as null. We called these alleles PI*S-plus because the S variant was phased with another variant conferring more aggressive characteristics to the allele. The current data demonstrate that the clinical variability observed in AATD can be explained by additional genetic variation, such as dual cis-acting variants in the SERPINA1 gene. The possible existence of other unrevealed variants combined in the PI*S alleles should be considered to improve the genetic diagnosis of the patients.

Lung cancer risk and residential radon exposure: A pooling of case-control studies in northwestern Spain.

BACKGROUND: Through a pooled case-control study design, we have assessed the relationship between residential radon exposure and lung cancer risk. Other objectives of the study were to evaluate the different risk estimates for the non-small cell lung cancer histological types and to assess the effect modification of the radon exposure on lung cancer risk by tobacco consumption. METHODS: We collected individual data from various case-control studies performed in northwest Spain that investigated residential radon and lung cancer. Cases had a confirmed anatomopathological diagnosis of primary lung cancer and controls were selected because they were undergoing ambulatory evaluation or surgical procedures that were unrelated to tobacco use. Residential radon was measured using alpha track detectors. Results were analyzed using logistic regression. RESULTS: 3704 participants were enrrolled, 1842 cases and 1862 controls. Data show that lung cancer risk increases with radon exposure, finding a significant association of radon exposure with lung cancer at radon exposures above 50 Bq/m3. The estimated adjusted OR for individuals exposed to concentrations >200 Bq/m3 was 2.06 (95% CI: 1.61-2.64) compared with those exposed to ≤50 Bq/m3. Within a smoking category, lung cancer risk increases markedly as radon concentration increases, reaching an OR of 29.3 (95% CI: 15.4-55.7) for heavy smokers exposed to more than 200 Bq/m.3 CONCLUSIONS: This study confirms that residential radon exposure is a risk factor for lung cancer well below action levels established by international organizations. As expected, there is also an effect modification between radon exposure and tobacco consumption.

The Importance of Reference Centers and Registries for Rare Diseases: The Example of Alpha-1 Antitrypsin Deficiency.

Alpha-1 antitrypsin deficiency (AATD) is a rare and underdiagnosed disease that is associated with the development of liver disease in adults and children and pulmonary emphysema in adults. Several studies have shown that there is limited knowledge about the disease and its diagnosis among health care providers, and there is an important inequity in the access to specialized care and appropriate treatment across Europe. The European Commision and the European Respiratory Society (ERS) recommend that the care of patients with AATD must be organized in reference centers at national or regional levels. These reference centers must provide optimal clinical care in terms of adequate diagnostic techniques, such as phenotyping and genotyping, and ensure access to treatment according to guidelines. Reference centers should also provide continuous medical education for health care professionals, genetic counseling, collaboration with patient associations and promote collaborative research and clinical trials with new and existing treatments for the disease. These centers must have a registry of their activity and collaborate with large, international, multicenter registries, such as the European Alpha-1 antitrypsin Deficiency Research Collaboration (EARCO) international registry, which is endorsed by the ERS, and aims to recruit up to 3,000 patients over a period of three years and prospectively follow them to better understand the natural history of the disease and the impact of different treatments on outcomes in a real life setting. International collaboration and standardized collection of high-quality prospective data will provide new insights into the clinical manifestations and prognosis of AATD.

Lung cancer risk and do-it-yourself activities. A neglected risk factor for lung cancer.

BACKGROUND: The aim of this study was to assess the relationship between do-it-yourself activities entailing the exposure to carcinogenic substances and the risk of lung cancer. METHODS: We pooled individual data from different case-control studies conducted in Northwestern Spain which investigated residential radon and lung cancer. Cases had an anatomopathologically confirmed primary lung cancer and controls were selected at the pre-surgery unit with uncomplicated surgeries. Both cases and controls were older than 30 years with no previous cancer history. All participants were interviewed face-to-face using a specific questionnaire. Painting, model building, furniture refinishing and woodworking or home carpentry were the do-it-yourself activities considered risky due to exposure to carcinogenic agents. RESULTS: We included 1528 cases and 1457 controls. Practicing do-it-yourself risk activities was more frequent among cases: 16.0% were exposed to carcinogenic exposures during leisure time, compared to 11.8% for controls. The overall adjusted OR for lung cancer risk among individuals who practiced do-it-yourself risk activities, was 1.77 (95% CI: 1.36-2.31); this was 2.17 (95% CI: 1.51-3.11) when the analysis was restricted to individuals who performed these activities for at least 10 years. These risks were greater when the analyses were carried out exclusively among never-smokers, with the respective ORs being 2.04 (95% CI: 1.38-3.01) and 3.10 (95% CI: 1.78-5.40). CONCLUSION: These results support the hypothesis that do-it-yourself activities involving exposure to certain carcinogens are associated with an increased risk of lung cancer, both in ever and never-smokers.

Lung cancer and residential radon in never-smokers: A pooling study in the Northwest of Spain.

BACKGROUND: Using a pooled case-control study design, including only never-smokers, we have assessed the association of residential radon exposure with the subsequent occurrence of lung cancer. We also investigated whether residential radon poses a different risk specifically for adenocarcinoma. METHODS: We pooled individual data from different case-control studies conducted in recent years in Northwestern Spain which investigated residential radon and lung cancer. All participants were never-smokers. Cases had a confirmed biopsy of primary lung cancer. Hospital controls were selected at pre-surgery units, presenting for non-complex surgical procedures. They were interviewed using a standardized instrument. Residential radon was measured using alpha track detectors at the Galician Radon Laboratory at the University of Santiago de Compostela. RESULTS: A total of 1415 individuals, 523 cases and 892 controls were included. We observed an odds ratio of 1.73 (95%CI: 1.27-2.35) for individuals exposed to ≥ 200 Bq/m3 compared with those exposed to ≤100 Bq/m3. Lung cancer risk for adenocarcinoma was 1.52 (95%CI: 1.14-2.02) using the same categories for radon exposure. CONCLUSIONS: Residential radon is a clear risk factor for lung cancer in never-smokers. Our data suggest that radon exposure is associated with all histological types of lung cancer and also with adenocarcinoma, which is currently the most frequent histological type for this disease.

Alcohol consumption and lung cancer risk in never smokers: a pooled analysis of case-control studies.

Background: Lung cancer is the deadliest cancer in developed countries but the etiology of lung cancer risk in never smokers (LCRINS) is largely unknown. We aim to assess the effects of alcohol consumption, in its different forms, on LCRINS. Methods: We pooled six multi-center case-control studies developed in the northwest of Spain. Cases and controls groups were composed of never smokers. We selected incident cases with anatomopathologically confirmed lung cancer diagnoses. All participants were personally interviewed. We performed two groups of statistical models, applying unconditional logistic regression with generalized additive models. One considered the effect of alcohol type consumption and the other considered the quantity of each alcoholic beverage consumed. Results: A total of 438 cases and 863 controls were included. Median age was 71 and 66, years, respectively. Adenocarcinoma was the predominant histological type, comprising 66% of all cases. We found that any type of wine consumption posed an OR of 2.20 OR 95%CI 1.12-4.35), and spirits consumption had an OR of 1.90 (95%CI 1.13-3.23). Beer consumption had an OR of 1.33 (95%CI 0.82-2.14). These results were similar when women were analyzed separately, but for men there was no apparent risk for any alcoholic beverage. The dose-response analysis for each alcoholic beverage revealed no clear pattern. Conclusions: Wine and spirits consumption might increase the risk of LCRINSs, particularly in females. These results have to be taken with caution given the limitations of the present study.

Residential radon, EGFR mutations and ALK alterations in never-smoking lung cancer cases.

The aim of this study was to assess if residential radon exposure might cause EGFR mutations or ALK rearrangements in never-smokers.We designed a multicentre case-control study in a radon-prone area (Galicia, Spain); only lung cancer cases were included in the study. We obtained residential radon measurements and clinical information for all the participants. We compared the median values of residential radon between patients with EGFR mutations or ALK rearrangements versus those without them.323 patients were included. Median age was 70 years and 19.5% were males. 42 and 15% of patients were EGFR- and ALK-positive, respectively. The most frequent EGFR alterations were exon 19 deletions and exon 21 (L858R) single-point substitution mutations. ALK-positive patients were 10 years younger than ALK-negative patients. Residential radon levels were two-fold higher in patients with exon 19 deletions compared with patients with exon 21 (L858R) single-point substitution mutations (216 versus 118 Bq·m-3; p=0.057). There were no differences in residential radon levels by EGFR mutation status. ALK-positive patients (n=12) essentially had two-fold residential radon levels compared with ALK-negative patients (290 versus 164 Bq·m-3, respectively).Residential radon may have a role in the molecular signature of lung cancer in never-smokers, although more studies with larger sample sizes are needed to support this hypothesis.

Small cell lung cancer in never-smokers.

Our aim was to describe the characteristics of a case-series of never-smoker small cell lung cancer (SCLC) cases.Cases of SCLC were selected from a prospective, multicenter, hospital-based case-control study performed in Spain. Participants were never-smokers older than 30 years with an anatomo-pathological confirmation of primary lung cancer. We collected clinical and epidemiological variables according to the study's protocol.We included 19 SCLC cases, 18 females (94.7%), median age 75 years (interquartile range (IQR) 70-80 years). Median residential radon concentration was 195 Bq·m(-3) (IQR 130-229 Bq·m(-3)). 10 patients had limited disease and nine had extended disease. Median survival was 242 days (IQR 94-496 days); 1- and 2-year survival were 36.8% and 17.6%, respectively. Survival was much higher for individuals with limited disease than for those with extended disease (median 336 versus 235 days; 1-year survival 50% versus 22.2% and 2-year survival 27% versus 0%, respectively). Performance status at diagnosis was closely related to survival.SCLC is an infrequent, highly aggressive disease in never-smokers. Survival is poor, even for limited disease. Age at diagnosis in SCLC is higher than that observed for never-smokers with adenocarcinoma. Residential radon exposure is higher than the action levels recommended by the World Health Organization.

Lung cancer in never-smokers: a case-control study in a radon-prone area (Galicia, Spain).

The aim of the study was to assess the effect of residential radon exposure on the risk of lung cancer in never-smokers and to ascertain if environmental tobacco smoke modifies the effect of residential radon. We designed a multicentre hospital-based case-control study in a radon-prone area (Galicia, Spain). All participants were never-smokers. Cases had an anatomopathologically confirmed primary lung cancer and controls were recruited from individuals undergoing minor, non-oncological surgery. Residential radon was measured using alpha track detectors. We included 521 individuals, 192 cases and 329 controls, 21% were males. We observed an odds ratio of 2.42 (95% CI 1.45-4.06) for individuals exposed to ≥200 Bq·m(-3) compared with those exposed to <100 Bq·m(-3). Environmental tobacco smoke exposure at home increased lung cancer risk in individuals with radon exposure>200 Bq·m(-3). Individuals exposed to environmental tobacco smoke and to radon concentrations>200 Bq·m(-3) had higher lung cancer risk than those exposed to lower radon concentrations and exposed to environmental tobacco smoke. Residential radon increases lung cancer risk in never-smokers. An association between residential radon exposure and environmental tobacco smoke on the risk of lung cancer might exist.

Leisure time activities related to carcinogen exposure and lung cancer risk in never smokers. A case-control study.

We aim to assess the relationship between leisure time activities related to exposure to carcinogenic substances and lung cancer risk in a hospital-based case-control study performed in never smokers. We included never smoking cases with anatomopathologically confirmed lung cancer and never smoking controls undergoing trivial surgery, at 8 Spanish hospitals. The study was conducted between January 2011 and June 2013. Participants were older than 30 and had no previous neoplasms. All were personally interviewed focusing on lifestyle, environmental tobacco smoke exposure, occupational history and leisure time activities (including duration of such activities). Results were analyzed through logistic regression and adjusted also by residential radon and education level. We included 513 never smokers, 191 cases and 322 controls. The OR for those performing the studied leisure time activities was 1.43 (95%CI 0.78-2.61). When we restricted the analysis to those performing do-it-yourself activities for more than 10 years the OR was 2.21 (95%CI 0.93-5.27). Environmental tobacco smoke exposure did not modify this association. The effect for the different lung cancer histological types was very close to significance for adenocarcinoma but only when these activities were performed for more than 10 years. We encourage health professionals to recommend protective measures for those individuals while performing these hobbies to reduce the risk of lung cancer.

Proposal and Definition of an Intelligent Clinical Decision Support System Applied to the Prediction of Dyspnea after 12 Months of an Acute Episode of COVID-19.

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.

Sex-Differences in Alpha-1 Antitrypsin Deficiency: Data From the EARCO Registry.

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.

Design and Conceptual Proposal of an Intelligent Clinical Decision Support System for the Diagnosis of Suspicious Obstructive Sleep Apnea Patients from Health Profile.

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.