Epidemiology of Lung Cancer Mortality in Spain: Updated Information (1982-2021) and Predictions up to 2046.

BACKGROUND: Patterns of lung cancer (LC) mortality are important for planning health services and resource management. OBJECTIVES: We aimed to provide updated information (1982-2021) and project (LC) mortality rates in Spain (2022-2046). METHOD: We analysed data from the Spanish National Statistics Institute about mortality in LC (1982-2021), and we made predictions for the period 2022-2046. RESULTS: In 2021, a total of 22,413 people died of LC, and for the period 2042-2046, the projected annual average was 25,549 deaths. In males, age-standardised mortality rates (ASMR) (overall) after an initial period of increase (1982-1996, 2.2%) declined until 2021 (-1.4% per year), and this decline is expected to continue in the future (-1.9% per year during the period 2022-2046), although the projected decline is slightly higher (-2.0% during the period 2022-2046). In men, ASMR (all ages) after an initial period of increase (1982-1996, 2.2%) declined until 2021 (-1.4% per year), and this decline is expected to continue in the future during the period 2022-2046. In women, both the overall and truncated rates (35-64) increase during the period 1982-2021 (4.1% and 6.0% per year, respectively), and projected rates showed that both will decrease during the period 2022-2046, although more markedly in the truncated rates (-1.9% per year) than in the overall rates (-0.5% per year). CONCLUSIONS: Our projections show the magnitude of a steady upward trend in LC mortality among women in Spain that appears to be beginning to reverse from the current decade (similar to that observed for incidence).

Chronic obstructive pulmonary disease mortality trends in Spain, 1980-2020.

OBJECTIVES: In Spain, there has been a recent increase in the mortality rate for chronic obstructive pulmonary disease (COPD) in younger women. This study aimed to analyze trends in the COPD mortality rate in Spain from 1980 to 2020, evaluating any differences between genders and age groups. METHODS: Death certificates and mid-year population data were obtained from the Spanish National Institute of Statistics. For both genders, age group-specific and standardized (overall and truncated) rates were calculated by the direct method using the world standard population. The data were analyzed using the joinpoint regression method. RESULTS: In both men and women, the number of COPD deaths increased from 1980 to 1999 (average annual increase of 7% in men and 4% in women), while from 1999 onwards, deaths decreased by -1.0% per year in both genders. In women, there was a significant final period of increase in the 55-59 to 70-74 age groups and a slowing of the decline in the over 75 age group. Additionally, an increase in mortality for the truncated rates was observed for women between 2006 and 2020. In men under 70 years of age, there was an initial period in which death rates remained stable or significantly increased, followed by a period in which they decreased significantly. CONCLUSIONS: Our study shows age and gender differences in COPD mortality trends in Spain. Although the data show a downward trend, we have identified a worrying increase in the truncated rates in women for the last few years.

Age-period-cohort effect on lung cancer mortality in Spain, 1982-2021.

BACKGROUND: The aim of the study is to provide up-to-date information and evaluate the age-period-cohort effects of age-period cohorts on lung cancer (LC) mortality in Spain for the period 1982 to 2021. METHODS: We analysed deaths by LC and population for the period 1982-2021, available from the Spanish National Institute of Statistics. The LC corresponds to code 162 and codes C33 and C34 of the 9th and 10th editions of the International Classification of Diseases, respectively. Age-period-cohort (A-P-C) modelling was applied to compute the net drift, local drift, longitudinal age curve, and rate ratios (RR) of each period and cohort. A-P-C analysis was performed using the A-P-C Web Tool provided by the National Cancer Institute of the United States. RESULTS: Estimated relative risk in the male birth cohorts has followed a steady downward trend in all cohorts born since 1922, showing an initial period (1922-1947) of slight decline, followed by a more marked decrease in the cohorts born during the period 1947-1977. In the younger cohorts (1977-1997), the decline appears to have stabilised. In women, a strong cohort effect is observed. In those born after the Spanish Civil War (1936 to 1939), the risk increased until it peaked in the 1960s, after which it started to decrease with the same intensity. Period RR in men decreased from 1987 to 1991 (1.1) to 2017-2021 (0.6), while period RR in women increased during this time (from 0.8 to 1.6). CONCLUSIONS: The cohort effect observed in women born after the Civil War suggests that the onset of the LC epidemic may have been due to a higher prevalence of women smokers in these cohorts. However, the trend observed in the younger cohorts suggests a possible slowing-down in the increase in mortality risk in the following years.

Prevalence of Obstructive Sleep Apnoea and Its Association With Atherosclerotic Plaques in a Cohort of Subjects With Mild-Moderate Cardiovascular Risk.

INTRODUCTION: Classic cardiovascular risk factors do not explain all the cardiovascular events. Obstructive sleep apnoea (OSA) has been proposed as a potential and prevalent cardiovascular risk factor. Our study aimed to describe the prevalence of OSA in a middle-aged cohort with mild-moderate cardiovascular risk and evaluate its association with atherosclerotic disease. METHODS: This is an observational cross-sectional ancillary study of the ILERVAS project which was aimed to study subclinical arterial disease in a cohort with mild-moderate cardiovascular risk. In a sample of consecutive subjects, we performed a sleep study and evaluate OSA prevalence and its association with carotid and femoral atheroma plaques and atherosclerotic burden. RESULTS: Overall, 966 subjects with a median age of 57 years (25-75th percentile; 52-62) and a body mass index (BMI) of 28.5kg/m2 (25.6-31.6) were included. Of these, 72.6% (69.7%-75.3%) had OSA (apnoea-hypopnoea index (AHI)≥5/h); 35.7% (32.8%-38.8%) had mild OSA (AHI 5-14.9/h) and 36.9% (33.9%-39.9%) had moderate/severe OSA (AHI≥15/h). Mean oxygen saturation and the percentage of time with oxygen saturation<90% (CT90) were associated with atherosclerotic burden (eß (95%CI) 0.932 (0.892, 0.974); 1.005 (1.002, 1.009), respectively) and total plaque (OR (95%CI) 0.88 (0.797,0.971); 1.013 (1.004,1.021), respectively). No association with the AHI or oxygen desaturation index was found. CONCLUSIONS: This study confirms a high prevalence of OSA in patients with mild-moderate cardiovascular risk and shows an association between atherosclerotic burden, total and femoral plaque with CT90 and mean oxygen saturation, suggesting the importance of OSA-related hypoxaemia in the induction of atherosclerotic disease.

Liraglutide Improves Forced Vital Capacity in Individuals With Type 2 Diabetes: Data From the Randomized Crossover LIRALUNG Study.

To evaluate the effect of liraglutide, a glucagon-like peptide 1 receptor agonist, on pulmonary function and serum levels of surfactant protein D (SP-D) in type 2 diabetes. A double-blind, randomized, crossover, placebo-controlled clinical trial comprising 76 patients with a baseline forced expiratory volume in 1 s <90% of that predicted. Liraglutide was administered for 7 weeks (2 weeks of titration plus 5 weeks at 1.8 mg daily). This short duration was intentional to minimize weight loss as a potential confounding factor. Serum level of SP-D was used as a biomarker of alveolar-capillary barrier integrity. Liraglutide exerted a positive impact on forced vital capacity (FVC) in comparison with placebo (ΔFVC 5.2% of predicted [from 0.8 to 9.6]; P = 0.009). No differences in the other pulmonary variables were observed. Participants under liraglutide treatment also experienced a decrease in serum SP-D (P = 0.038). The absolute change in FVC correlated with final serum SP-D in participants receiving liraglutide (r = -0.313, P = 0.036). Stepwise multivariate regression analysis showed that final serum SP-D independently predicted changes in FVC. In conclusion, liraglutide increased FVC in patients with type 2 diabetes. This effect was associated with a significant decrease of circulating SP-D, thus pointing to a beneficial effect in the alveolar-capillary function.

Obstructive sleep apnoea and cognitive decline in mild-to-moderate Alzheimer's disease.

We evaluated the influence of untreated obstructive sleep apnoea (OSA) on the magnitude of cognitive decline and on several cognitive subdomains in patients with mild-to-moderate Alzheimer's disease.In this single-centre study, 144 patients were recruited prospectively from a cognitive impairment unit and underwent overnight polysomnography.The mean±sd change in the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) score at 12 months was 3.19±5.61 in the non-OSA group and 0.08±5.62 in the OSA group, with an intergroup difference of -3.36 (95% CI 0.19-0.16; p=0.002). We did not observe a significant difference in any cognitive subdomains at 12 months. Regarding Mini-Mental State Examination scores at 36 months, the mean change was 1.69 (95% CI -1.26-4.64; p=0.445). No significant differences were found among different OSA severity groups.We observed that ADAS-cog scores were better in the OSA group than in the non-OSA group by a statistically but not clinically significant margin. We did not find differences in the different cognitive subdomains after 1 year or in global cognition after 3 years of follow-up.

Prevalence of obstructive sleep apnea in Alzheimer's disease patients.

OBJECTIVE: To assess the prevalence of obstructive sleep apnea (OSA) in patients with mild-moderate Alzheimer's Disease (AD) and to evaluate cognitive characteristics according to the severity of OSA. METHODS: Patients with mild-moderate AD, recruited prospectively from a cognitive impairment unit, underwent overnight polysomnography. OSA was defined as an apnea-hypopnea index > 5/h. AD severity was assessed using the Mini-Mental State Examination and extensive neuropsychological battery. Epworth Sleepiness Scale and APOE status were analyzed. RESULTS: The cohort included 128 patients with a median [IQR] age of 75.0 [72.0;79.2] years and 57.8% were women. OSA was diagnosed in 116 subjects (90.6%). The distribution of mild, moderate and severe severity of OSA was 29 (22.7%), 37 (28.9%) and 50 (39.1%), respectively. Regarding sleep symptoms, the cohort showed normal values of daytime sleepiness (median EES score 5 [3, 8]), while nycturia (89.1%) and snoring (71.1%) were the most common symptoms. Participants with severe OSA included a higher proportion of older men, were associated with snoring and sedentariness. No significant differences in cognitive assessment were found between patients with and without severe OSA in any of the domains. The prevalence of APOE ε4 was not significantly different between patients with and without severe OSA. CONCLUSION: There was a high prevalence of OSA in patients with mild-moderate AD. OSA was not associated with sleepiness or worse cognitive function. APOE ε4 was not related to the presence or severity of OSA. Further longitudinal studies will be required to evaluate whether OSA impairs cognitive evolution in AD patients.

Prevalence, Characteristics, and Association of Obstructive Sleep Apnea with Blood Pressure Control in Patients with Resistant Hypertension.

Rationale: Obstructive sleep apnea (OSA) is associated with poor blood pressure (BP) control and resistant hypertension (RH). Nevertheless, studies assessing its prevalence, characteristics, and association with BP control in patients with RH are limited.Objectives: The aim of this multicenter study was to assess the prevalence of OSA in a large cohort of subjects with RH and to evaluate the association of OSA with BP control.Methods: We recruited consecutive subjects with RH from three countries. A formal sleep test and blood pressure measurements, including 24-hour ambulatory blood pressure monitoring, were performed in all participants.Results: In total, 284 subjects with RH were included in the final analysis. Of these, 83.5% (95% confidence interval [CI], 78.7-87.3%) had OSA (apnea-hypopnea index ≥ 5 events/h); 31.7% (95% CI, 26.5-37.3%) had mild OSA, 25.7% (95% CI, 21-31.1%) had moderate OSA, and 26.1% (95% CI, 21.3-31.5%) had severe OSA. Patients with severe OSA had higher BP values than subjects with mild to moderate or no OSA. A greater effect was observed on the average nighttime BP, with an adjusted effect of 5.72 mm Hg (95% CI, 1.08-10.35 mm Hg) in severe OSA compared with participants without OSA. A dose-response association between the severity of OSA and BP values was observed. The prevalence of severe OSA was slightly higher in uncontrolled participants (adjusted odds ratio, 1.69; 95% CI, 0.97-2.99) but was not statistically significant.Conclusions: The present study confirms the high prevalence of OSA in participants with RH. Furthermore, it shows a dose-response association between OSA severity and BP measurements, especially in the nighttime.Clinical trial registered with www.clinicaltrials.gov (NCT03002558).

Lung function measurements in the prediabetes stage: data from the ILERVAS Project.

AIMS: Patients with type 2 diabetes have been considered a susceptible group for pulmonary dysfunction. Our aim was to assess pulmonary function on the prediabetes stage. METHODS: Pulmonary function was assessed in 4,459 non-diabetic subjects, aged between 45 and 70 years, without cardiovascular disease or chronic pulmonary obstructive disease from the ongoing study ILERVAS. A "restrictive spirometric pattern", an "abnormal FEV1" and an "obstructive ventilatory defect" were assessed. Prediabetes was defined by glycosylated hemoglobin (HbA1c) between 5.7 and 6.4% according to the American Diabetes Association criteria. RESULTS: Population was composed of 52.1% women, aged 57 [53;63] years, a BMI of 28.6 [25.8;31.8] kg/m2, and with a prevalence of prediabetes of 29.9% (n = 1392). Subjects with prediabetes had lower forced vital capacity (FVC: 93 [82;105] vs. 96 [84;106], p < 0.001) and lower forced expired volume in the first second (FEV1: 94 [82;107] vs. 96 [84;108], p = 0.011), as well as a higher percentage of the restrictive spirometric pattern (16.5% vs. 13.6%, p = 0.015) and FEV1 < 80% (20.3% vs. 17.2%, p = 0.017) compared to non-prediabetes group. In the prediabetes group, HbA1c was negatively correlated with both pulmonary parameters (FVC: r = - 0.113, p < 0.001; FEV1: r = - 0.079, p = 0.003). The multivariable logistic regression model in the whole population showed that there was a significant and independent association between HbA1c with both restrictive spirometric pattern [OR = 1.42 (1.10-1.83), p = 0.008] and FEV1 < 80% [OR = 1.50 (1.19-1.90), p = 0.001]. CONCLUSIONS: The deleterious effect of type 2 diabetes on pulmonary function appears to be initiated in prediabetes, and it is related to metabolic control. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT03228459.

The STOP-Bang and Berlin questionnaires to identify obstructive sleep apnoea in Alzheimer's disease patients.

BACKGROUND: A close relationship between obstructive sleep apnoea (OSA) and Alzheimer's disease (AD) has been described in recent years. OSA is a risk factor for AD, but the diagnosis and clinical characteristics of OSA in patients with AD is not well understood. This study evaluated the clinical utility of two screening questionnaires, the STOP-Bang questionnaire (SBQ) and the Berlin questionnaire (BQ), to identify which patients with mild AD are at higher risk of having OSA and to determine the clinical predictors of OSA in this population. METHODS: In this study, 91 consecutive outpatients with mild AD were prospectively evaluated with the SBQ and the BQ. All patients underwent level 1 in-laboratory polysomnography. The predictive performance of the questionnaires were calculated for different apnoea-hypopnoea index (AHI) cut-offs. RESULTS: The median age of the patients was 76.0 (73.0; 80.0) years, and 58 (63.7%) were female. Of those, 81 patients (89.02%) were found to have OSA defined by an AHI > 5 events/h. Comparing the predictive performances of the SBQ and the BQ, the SBQ was found to have a higher diagnostic sensitivity (85% vs 4%), a lower specificity (35% vs. 96%), a higher positive predictive value (PPV) (44% vs 33%) and negative predictive value (NPV) (80% vs 65%) for detecting severe OSA at an AHI cut-off of 30 events/h. None of the items alone in the two questionnaires predicted the risk of OSA. A modified version of the SBQ, with new cut-off points for several variables according to the characteristics of AD patients, showed a slightly greater AUC than the standard SBQ (AUC 0.61 vs 0.72). CONCLUSION: There is a high prevalence of OSA among patients with mild AD. The SBQ and the BQ are not good screening tools for detecting OSA in patients with AD. A modified version of SBQ could increase the detection of these patients.

Effects of Mediterranean Diet and Physical Activity on Pulmonary Function: A Cross-Sectional Analysis in the ILERVAS Project.

A few studies showed that both adherence to Mediterranean diet (MedDiet) and physical activity practice have a positive impact on pulmonary function in subjects with lung disease. These associations are not well studied in subjects free from lung disease. In a cross-sectional study conducted in 3020 middle-aged subjects free of lung disease, adherence to the MedDiet using the Mediterranean Diet Adherence Screener, and physical activity practice using the International Physical Activity Questionnaire short form were recorded. Respiratory function was assessed using forced spirometry and the results were evaluated according to the Global initiative for Chronic Obstructive Lung Disease. Logistic regression models were used to analyze the associations between adherence to the MedDiet and physical activity practice with the presence of ventilatory defects. Participants with a high adherence to MedDiet, in comparison to those with low adherence, had both higher forced vital capacity (FVC; 100 (87⁻109) vs. 94 (82⁻105) % of predicted, p = 0.003) and forced expired volume in the first second (FEV1; 100 (89⁻112) vs. 93 (80⁻107) % of predicted, p < 0.001). According to their degree of physical activity, those subjects with a high adherence also had both higher FVC (100 (88⁻107) vs. 94 (83⁻105) % of predicted, p = 0.027) and FEV1 (100 (89⁻110) vs. 95 (84⁻108) % of predicted, p = 0.047) in comparison with those with low adherence. The multivariable logistic regression models showed a significant and independent association between both low adherence to MedDiet and low physical activity practice, and the presence of altered pulmonary patterns, with differences between men and women. However, no joint effect between adherence to MedDiet and physical activity practice on respiratory function values was observed. Low adherence to MedDiet and low physical activity practice were independently associated with pulmonary impairment. Therefore, the lung mechanics seem to benefit from heart-healthy lifestyle behaviors.

The influence of sleep apnea syndrome and intermittent hypoxia in carotid adventitial vasa vasorum.

Subjects with sleep apnea-hypopnea syndrome (SAHS) show an increased carotid intima-media thickness. However, no data exist about earlier markers of atheromatous disease, such as the proliferation and expansion of the adventitial vasa vasorum (VV) to the avascular intima in this setting. Our aim was to assess carotid VV density and its relationship with sleep parameters in a cohort of obese patients without prior vascular events. A total of 55 subjects evaluated for bariatric surgery were prospectively recruited. A non-attended respiratory polygraphy was performed. The apnea-hypopnea index (AHI) and the cumulative percentage of time spent with oxygen saturation below 90% (CT90) were assessed. Serum concentrations of soluble intercellular adhesion molecule 1, P-selectin, lipocalin-2 and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured. Contrast-enhanced carotid ultrasound was used to assess the VV density. Patients with SAHS (80%) showed a higher adventitial VV density (0.801±0.125 vs. 0.697±0.082, p = 0.005) and higher levels of sVCAM-1 (745.2±137.8 vs. 643.3±122.7 ng/ml, p = 0.035) than subjects with an AHI lower than 10 events/hour. In addition, a positive association exist between mean VV density and AHI (r = 0.445, p = 0.001) and CT90 (r = 0.399, p = 0.005). Finally, in the multiple linear regression analysis, female sex, fasting plasma glucose and AHI (but not CT90) were the only variables independently associated with the mean adventitial VV density (R2 = 0.327). In conclusion, a high VV density is present in obese subjects with SAHS, and chronic intermittent hypoxia is pointed as an independent risk factor for the development of this early step of atheromatous disease.

Continuous noninvasive ventilation for respiratory failure in patients with amyotrophic lateral sclerosis: current perspectives.

Respiratory failure is a recognized late complication of amyotrophic lateral sclerosis. It is related to the neurological progression of the diseases with the impairment of the respiratory musculature. Survival and quality of life of amyotrophic lateral sclerosis patients is improved by using noninvasive mechanical ventilation. The rate of long-term mechanical ventilation is different within and between countries. Cultural factors, socioeconomic conditions, and physician attitude often influence the decision to start noninvasive ventilation. Technical elements, like the choice of the correct interface, solid caregivers support, and the communication between the patient and the physician are essential for achieving therapeutic goals, especially in the case of continuous treatment.