Clinical, radiological and functional outcomes in patients with SARS-CoV-2 pneumonia: a prospective observational study.

BACKGROUND: All over the world, SARS-CoV-2 pneumonia is causing a significant short-term morbidity and mortality, but the medium-term impact on lung function and quality of life of affected patients are still unknown. METHODS: In this prospective observational study, 39 patients with SARS-CoV-2 pneumonia were recruited from a single COVID-19 hospital in Southern Switzerland. At three months patients underwent radiological and functional follow-up through CT scan, lung function tests, and 6 min walking test. Furthermore, quality of life was assessed through self-reported questionnaires. RESULTS: Among 39 patients with SARS-CoV-2 pneumonia, 32 (82% of all participants) presented abnormalities in CT scan and 25 (64.1%) had lung function tests impairment at three months. Moreover, 31 patients (79.5%) reported a perception of poor health due to respiratory symptoms and all 39 patients showed an overall decreased quality of life. CONCLUSIONS: Medium-term follow up at three months of patients diagnosed with SARS-CoV-2 pneumonia shows the persistence of abnormalities in CT scans, a significant functional impairment assessed by lung function tests and a decreased quality of life in affected patients. Further studies evaluating the long-term impact are warranted to guarantee an appropriate follow-up to patients recovering from SARS-CoV-2 pneumonia.

SERPINA1 methylation and lung function in tobacco-smoke exposed European children and adults: a meta-analysis of ALEC population-based cohorts.

BACKGROUND: The pathophysiological role of SERPINA1 in respiratory health may be more strongly determined by the regulation of its expression than by common genetic variants. A family based study of predominantly smoking adults found methylation at two Cytosine-phosphate-Guanine sites (CpGs) in SERPINA1 gene to be associated with chronic obstructive pulmonary disease risk. The objective of this study was to confirm the association of lung function with SERPINA1 methylation in general population samples by testing a comprehensive set of CpGs in the SERPINA gene cluster. We considered lung function level and decline in adult smokers from three European population-based cohorts and lung function level and growth in tobacco-smoke exposed children from a birth cohort. METHODS: DNA methylation using Illumina Infinium Human Methylation 450 k and EPIC beadchips and lung function were measured at two time points in 1076 SAPALDIA, ECRHS and NFBC adult cohort participants and 259 ALSPAC children. Associations of methylation at 119 CpG sites in the SERPINA gene cluster (PP4R4-SERPINA13P) with lung functions and circulating alpha-1-antitripsin (AAT) were assessed using multivariable cross-sectional and longitudinal regression models. RESULTS: Methylation at cg08257009 in the SERPINA gene cluster, located 32 kb downstream of SERPINA1, not annotated to a gene, was associated with FEV1/FVC at the Bonferroni corrected level in adults, but not in children. None of the methylation signals in the SERPINA1 gene showed associations with lung function after correcting for multiple testing. CONCLUSIONS: The results do not support a role of SERPINA1 gene methylation as determinant of lung function across the life course in the tobacco smoke exposed general population exposed.

Associations between Dietary Patterns and Post-Bronchodilation Lung Function in the SAPALDIA Cohort.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is not restricted to smokers. Dietary habits may contribute to the disease occurrence. Epidemiological studies point to a protective effect of fruit and vegetable intake against COPD. OBJECTIVE: To investigate the associations between dietary patterns and parameters of lung function related to COPD in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA). METHODS: Data were included from the second follow-up assessment of the SAPALDIA cohort in 2010-2011 using a food frequency questionnaire. Principal component factor analysis was used to derive dietary patterns, whose association with FEV1, FEV1/FVC, FEF2575, and COPD was investigated by applying multivariate regression analyses. RESULTS: After adjustment for potential confounders, the "prudent dietary pattern" characterised by the predominant food groups vegetables, fruits, water, tea and coffee, fish, and nuts was positively associated with FEV1 (increase of 40 mL per SD, p < 0.001). Also for factor 3 ("high-carbohydrate diet"), we found a significant positive association with FEV1 (with an increase per SD of 36 mL, p = 0.006). CONCLUSIONS: The main results are consistent with a protective effect of a diet rich in fruits, vegetables, fish, and nuts against age-related chronic respiratory disease. If confirmed in prospective cohorts, our results may guide nutritional counselling towards respiratory health promotion.

Health-related quality of life and risk factors associated with spirometric restriction.

The restrictive spirometric pattern is associated with a substantial morbidity and mortality burden. We sought to determine to what extent spirometric restriction is associated with impaired quality of life.We used data from two large population-based European cohorts: 6698 European Community Respiratory Health Survey (ECRHS) and 6069 Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) adult participants. The restrictive pattern was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥lower limit of normal (LLN) and FVC

Hypertension, diabetes and lifestyle in the long-term - Results from a Swiss population-based cohort.

Healthy lifestyles are integral in preventing and treating common cardiovascular and metabolic diseases. The aim of this study was to observe smoking habits, alcohol intake, physical activity and body mass index over a 10-year period in a population-based cohort, particularly focusing on participants with hypertension and type 2 diabetes mellitus. Included were 4155 participants from the first (2001-2003) and second (2010-2011) follow-ups of the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults (SAPALDIA). Information was collected via health questionnaire; height and weight were measured. In a healthy lifestyle score one point was attributed per criterion; non-smoking, low risk alcohol consumption, BMI<25kg/m2, and regular physical activity. Overall in 2010-2011, 16.4% were smokers, 7.7% had at risk alcohol consumption, 25.5% were physically inactive and 57.8% were overweight or obese. Both those with hypertension and diabetes had lower mean healthy lifestyle scores than those without disease. Women with incident hypertension from 2001 to 2011 had lower odds of improving their healthy lifestyle score during this time period compared to those without this disease. In contrast, women with incident diabetes had higher odds of lifestyle score improvement. In men, neither hypertension nor diabetes was associated with change in lifestyle score. Our findings suggest that, irrespective of disease status, preventative attention is needed, particularly in regards to physical activity and bodyweight. These needs could be met by population-based interventions, a necessary and suitable option in both preventing and treating the non-communicable disease epidemic which currently faces countries worldwide.

Physical activity is associated with lower arterial stiffness in older adults: results of the SAPALDIA 3 Cohort Study.

Associations of physical activity (PA) intensity with arterial stiffness in older adults at the population level are insufficiently studied. We examined cross-sectional associations of self-reported PA intensities with arterial stiffness in elderly Caucasians of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults. Mixed central and peripheral arterial stiffness was measured oscillometrically by the cardio-ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV). The self-reported International Physical Activity Questionnaire long version was administered to classify each subject's PA level. We used univariable and multivariable mixed linear and logistic regression models for analyses in 1908 persons aged 50 years and older. After adjustment for several confounders moderate, vigorous and total PA were inversely associated with CAVI (p = 0.02-0.03). BaPWV showed negative and marginally significant associations with vigorous and moderate PA (each p = 0.06), but not with total PA (p = 0.28). Increased arterial stiffness (CAVI ≥ 9, upper tertile) was inversely and significantly associated with vigorous PA [odds ratio (OR) 0.65, 95% confidence interval (CI) 0.48-0.88], and marginally significantly with total PA (OR 0.76, 95% CI 0.57-1.02) and moderate PA (OR 0.75, 95% CI 0.56-1.01). The odds ratio for baPWV ≥ 14.4 was 0.67 (95% CI 0.48-0.93) across the vigorous PA levels, and was non-significant across the total (OR 0.91, 95% CI 0.66-1.23) and moderate PA levels (OR 0.94, 95% CI 0.69-1.28). In this general Caucasian population of older adults higher levels especially of vigorous PA were associated with lower arterial stiffness. These data support the importance of PA for improving cardiovascular health in elderly people.

Long-term physical activity is associated with reduced arterial stiffness in older adults: longitudinal results of the SAPALDIA cohort study.

BACKGROUND: longitudinal analyses of physical activity (PA) and arterial stiffness in populations of older adults are scarce. We examined associations between long-term change of PA and arterial stiffness in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA). METHODS: we assessed PA in SAPALDIA 2 (2001-03) and SAPALDIA 3 (2010-11) using a short questionnaire with a cut-off of at least 150 min of moderate-to-vigorous PA per week for sufficient activity. Arterial stiffness was measured oscillometrically by means of the brachial-ankle pulse wave velocity (baPWV) in SAPALDIA 3. We used multivariable mixed linear regression models adjusted for several potential confounders in 2,605 persons aged 50-81. RESULTS: adjusted means of baPWV were significantly lower in persons with sufficient moderate-to-vigorous PA (i) in SAPALDIA 2 but not in SAPALDIA 3 (P = 0.048) and (ii) in both surveys (P = 0.001) compared with persons with insufficient activity in both surveys. There was a significant interaction between sex and the level of change in PA concerning baPWV (P = 0.03). The triples of parameter estimates describing the association between level of PA change and baPWV were not significantly different between the two sex-specific models (P = 0.07). CONCLUSIONS: keeping up or adopting a physically active lifestyle was associated with lower arterial stiffness in older adults after a follow-up of almost a decade. Increasing the proportion of older adults adhering to PA recommendations incorporating also vigorous PA may have a considerable impact on vascular health at older age and may contribute to healthy ageing in general.

Spirometer Replacement and Serial Lung Function Measurements in Population Studies: Results From the SAPALDIA Study.

The Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults (SAPALDIA), a population cohort study, used heated-wire spirometers in 1991 and 2002 and then ultrasonic spirometers in 2010 revealing measurement bias in healthy never smokers. To provide a practical method to control for measurement bias given the replacement of spirometer in long-term population studies, we built spirometer-specific reference equations from healthy never smokers participating in 1991, 2002, and 2010 to derive individualized corrections terms. We compared yearly lung function decline without corrections terms with fixed terms that were obtained from a quasi-experimental study and individualized terms. Compared with baseline reference equations, spirometer-specific reference equations predicted lower lung function. The mean measurement bias increased with age and height. The decline in forced expiratory volume in 1 second during the reference period of 1991-2002 was 31.5 (standard deviation (SD), 28.7) mL/year while, after spirometer replacement, uncorrected, corrected by fixed term, and individualized term, the declines were 47.0 (SD, 30.1), 40.4 (SD, 30.1), and 30.4 (SD, 29.9) mL/year, respectively. In healthy never smokers, ultrasonic spirometers record lower lung function values than heated-wire spirometers. This measurement bias is sizeable enough to be relevant for researchers and clinicians. Future reference equations should account for not only anthropometric variables but also spirometer type. We provide a novel method to address spirometer replacement in cohort studies.

Gender differences in adult-onset asthma: results from the Swiss SAPALDIA cohort study.

A higher incidence of asthma is reported in women compared with men, but evidence in later adulthood is limited. We aimed to determine the 20-year cumulative incidence of adult asthma in Switzerland and its relation to sex, taking into account age and allergic sensitisation.We assessed incidence of self-report of doctor-diagnosed asthma between 1991/1992 and 2010/2011 in 5128 subjects without asthma, aged 18-60 years at baseline. The age-related probability of asthma onset was analysed by logistic regression adjusting for potential confounders and stratified by sex and allergic sensitisation at baseline.Over 20 years, 128 (5.1%) men and 198 (7.5%) women newly reported doctor-diagnosed asthma. The adjusted odds ratio for female sex was 1.99 (95% CI 1.54-2.57) overall, 3.21 (95% CI 2.12-4.85) among nonsensitised subjects, and 1.43 (95% CI 1.02-2.02) in sensitised subjects. The probability of asthma onset decreased with increasing baseline age in women but not in men. The higher probability of new asthma in sensitised compared with nonsensitised men was unrelated to age, whereas in women it decreased with age.Asthma incidence was higher in women than in men but decreased with increasing age. The female predominance was considerably stronger in nonsensitised adults compared with those with allergic sensitisation.

Long-term smoking cessation and heart rate dynamics in an aging healthy cohort: Is it possible to fully recover?

AIM: To evaluate the long-term influence of smoking cessation on the regulation of the autonomic cardiovascular system in an aging general population, using the subpopulation of lifelong non-smokers as control group. METHODS: We analyzed 1481 participants aged ≥50 years from the SAPALDIA cohort. In each participant, heart rate variability and heart rate dynamics were characterized by means of various quantitative analyzes of the inter-beat interval time series generated from 24-hour electrocardiogram recordings. Each parameter obtained was then used as the outcome variable in multivariable linear regression models in order to evaluate the association with smoking status and time elapsed since smoking cessation. The models were adjusted for known confounding factors and stratified by the time elapsed since smoking cessation. RESULTS: Our findings indicate that smoking triggers adverse changes in the regulation of the cardiovascular system, even at low levels of exposure since current light smokers exhibited significant changes as compared to lifelong non-smokers. Moreover, there was evidence for a dose-response effect. Indeed, the changes observed in current heavy smokers were more marked as compared to current light smokers. Furthermore, full recovery was achieved in former smokers (i.e., normalization to the level of lifelong non-smokers). However, while light smokers fully recovered within the 15 first years of cessation, heavy former smokers might need up to 15-25 years to fully recover. CONCLUSION: This study supports the substantial benefits of smoking cessation, but also warns of important long-term alterations caused by heavy smoking.

Assessing the impact of bibliographical support on the quality of medical care in patients admitted to an internal medicine service: a prospective clinical, open, randomised two-arm parallel study.

UNLABELLED: To assess and quantify the impact of the literature in diagnostic decisions and treatment of patients admitted to an internal medicine service using the methodology of evidence-based medicine. From November 2012 to February 2013, patients who were hospitalised in the internal medicine service of Regional Hospital of Lugano (Switzerland) and generated questions on medical care were randomly assigned to two groups: an 'intervention group' (supported by the literature research) and a 'control group' (not supported by the literature research). The information obtained from the literature was submitted by email to all members of the medical team within 12 h after asking the question. Two hundred and one participants, from 866 patients hospitalised in the analysed period, divided into intervention (n=101) and control (n=100) groups, generated questions. In the intervention group, bibliographical research was possible for 98 participants. The medical team accepted the results and implemented the research for 90.8% of these participants (89/98). Statistical analyses were carried out on the intention-to-treat and on the per-protocol populations. Bibliographical research had a significant protective effect on transfer to an intensive care unit (relative risk (RR)=0.30; 95% CI 0.10 to 0.90; χ²=5.3, p=0.02) and hospital readmissions were also influenced by bibliographical research (RR=0.42; 95% CI 0.17 to 1.0; χ²=3.36, p=0.05) in the intention-to-treat population. Our results point out the importance of bibliographical support on the quality of medical care. In particular, they show its possible impact on clinical outcome. TRIAL REGISTRATION NUMBER: EOC Registry (registration number: 14-055).

Contemporary adequacy of thromboprophylaxis in acutely ill medical patients in Switzerland: a bi-centric prospective cohort.

BACKGROUND: Venous thromboembolism is a dreaded complication of hospitalised patients, with associated morbidity, mortality and increased healthcare costs. Previous studies have shown that pharmacological thromboprophylaxis, though effective, is inadequately administered in a large proportion of medical inpatients. STUDY AIMS: Our primary aim was to evaluate the contemporary adequacy of thromboprophylaxis in medical inpatients admitted to two Swiss hospitals (a university hospital and a regional hospital). The secondary aim was to estimate the 90-day incidence of relevant thrombotic and bleeding events. METHODS: In this prospective cohort, patients were recruited at the University Hospital of Geneva and the Regional Hospital of Lugano between September 2020 and February 2021 and followed for 90 days for venous thromboembolism and bleeding events. The adequacy of thromboprophylaxis (pharmacological and/or mechanical) at 24h after hospital admission was evaluated according to the simplified Geneva risk score for hospital-associated venous thromboembolism. RESULTS: Among 200 participants (100 at each site, mean age of 65 years), 57.5% were deemed at high risk of venous thromboembolism at admission. Thromboprophylaxis was adequate in 59.5% (95% CI 52.3-66.4%). Among high-risk and low-risk inpatients, thromboprophylaxis was adequate in 71.3% and 43.5%, respectively, with differences between sites. At 90 days, risks of adjudicated venous thromboembolism, major bleeding and mortality were 1.5%, 1.5% and 6.0%, respectively. CONCLUSION: Despite the extensive literature on thromboprophylaxis, the adequacy of thromboprophylaxis has not improved and remains insufficient among medical inpatients. Implementation and evaluation of clinical decision support systems are critically needed in this field. CLINICALTRIALS: gov number: NCT05306821.

Hypercalcemia: An Underestimated Value Always Good for a Surprise.

We present the unusual case of a 62-year-old male with profound asthenia and dyspnea for the last two months. Blood exams showed a severe hypercalcemia. Suspecting an underlying malignancy, we performed a 18F-FDG PET-CT, revealing widespread metabolic uptakes in muscles, consistent with an inflammatory process. The muscular biopsy showed a non-necrotising granuloma with multinucleated giant cells, pathognomonic for the diagnosis of acute isolated muscular sarcoidosis. A high-dose steroid therapy was started with clinical improvement and serum calcium normalization.

1-year radiological, functional and quality-of-life outcomes in patients with SARS-CoV-2 pneumonia - A prospective observational study.

All over the world, SARS-CoV-2 pneumonia is causing a significant short and medium-term morbidity and mortality, with reported persisting symptoms, radiological and lung alterations up to 6 months after symptoms onset. Nevertheless, the 1-year impact on affected patients is still poorly known. In this prospective observational study, 39 patients with SARS-CoV-2 pneumonia were recruited from a single COVID-19 hospital in Southern Switzerland. They underwent a 3-month and 1-year follow-ups. At 1 year, 38 patients underwent functional follow-up through lung function tests and six minutes walking test and submitted SF-12 and SGRQ questionnaires about health-related quality of life. At 1 year most of the patients showed a persistence of the radiological and functional abnormalities and a reduction of the health-related quality of life. Thirty patients (96.8%) still presented some residual abnormalities on CT scans (31 patients at 3 months), though with a general reduction of the lesional load in all lung lobes. Twenty patients (52.6%) had persisting lung function tests impairment, with an overall improvement of DLCO. As concerning the functional status, lowest SpO2 during 6MWT increased significantly. Finally, 19 patients (50%) reported a pathological St. George's Respiratory Questionnaire, and respectively 12 (31.6%) and 11 (28.9%) patients a pathological Short Form Survey-12 in physical and mental components. At 1-year follow-up SARS-CoV-2 pneumonia survivors still present a substantial impairment in radiological and functional findings and in health-related quality of life, despite showing a progressive recovery.

Obstructive and Central Sleep Apnea in First Ever Ischemic Stroke are Associated with Different Time Course and Autonomic Activation.

INTRODUCTION: Sleep-related breathing disorders are highly prevalent in patients with ischemic stroke. Among sleep-disordered breathing disorders, obstructive sleep apnea is the most represented one, but central sleep apnea, isolated or in the context of a periodic breathing/Cheyne-Stokes respiration, is frequently reported in these patients. Altered baroreflex responses have been reported in the acute phases of a cerebral event. METHODS: We conducted, in a group of patients with ischemic stroke (n=60), a prospective 3-month follow-up physiological study to describe the breathing pattern during sleep and baroreflex sensitivity in the acute phase and in the recovery phase. RESULTS: In the acute phase, within 10 days from the onset of symptoms, 22.4% of patients had a normal breathing pattern, 40.3% had an obstructive pattern, 16.4% had a central pattern, and 29.9% showed a mixed pattern. Smaller variations in the Apnea-Hypopnea Index were found in normal breathing and obstructive groups (ΔAHI 2.1±4.1 and -2.8±11.6, respectively) in comparison with central and mixed patterns (ΔAHI -6.9±15.1 and -12.5±13.1, respectively; ANOVA p=0.01). The obstructive pattern became the most frequent pattern, in 38.3% of patients at baseline and 61.7% of patients at follow-up. Modification of baroreflex sensitivity over time was influenced by the site of the lesion and by the sleep disorder pattern in the acute phase (MANOVA p=0.005). CONCLUSION: We suggest that a down-regulation of autonomic activity, possibly related to reduced vagal modulation, may help the recovery after stroke, or a transitory disconnection from the cortical node that participates in the regulation of sympathetic outflow.

Causal Effects of Body Mass Index on Airflow Obstruction and Forced Mid-Expiratory Flow: A Mendelian Randomization Study Taking Interactions and Age-Specific Instruments Into Consideration Toward a Life Course Perspective.

Obesity has complex links to respiratory health. Mendelian randomization (MR) enables assessment of causality of body mass index (BMI) effects on airflow obstruction and mid-expiratory flow. In the adult SAPALDIA cohort, recruiting 9,651 population-representative samples aged 18-60 years at baseline (female 51%), BMI and the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) as well as forced mid-expiratory flow (FEF25-75%) were measured three times over 20 follow-up years. The causal effects of BMI in childhood and adulthood on FEV1/FVC and FEF25-75% were assessed in predictive (BMI averaged over 1st and 2nd, lung function (LF) averaged over 2nd and 3rd follow-up; N = 2,850) and long-term cross-sectional models (BMI and LF averaged over all follow-ups; N = 2,728) by Mendelian Randomization analyses with the use of weighted BMI allele score as an instrument variable and two-stage least squares (2SLS) method. Three different BMI allele scores were applied to specifically capture the part of BMI in adulthood that likely reflects tracking of genetically determined BMI in childhood. The main causal effects were derived from models containing BMI (instrumented by BMI genetic score), age, sex, height, and packyears smoked as covariates. BMI interactions were instrumented by the product of the instrument (BMI genetic score) and the relevant concomitant variable. Causal effects of BMI on FEV1/FVC and FEF25-75% were observed in both the predictive and long-term cross-sectional models. The causal BMI- LF effects were negative and attenuated with increasing age, and stronger if instrumented by gene scores associated with childhood BMI. This non-standard MR approach interrogating causal effects of multiplicative interaction suggests that the genetically rooted part of BMI patterns in childhood may be of particular relevance for the level of small airway function and airflow obstruction later in life. The methodological relevance of the results is first to point to the importance of a life course perspective in studies on the etiological role of BMI in respiratory health, and second to point out novel methodological aspects to be considered in future MR studies on the causal effects of obesity related phenotypes.

Improvements in PM10 exposure and reduced rates of respiratory symptoms in a cohort of Swiss adults (SAPALDIA).

RATIONALE: Reductions in mortality following improvements in air quality were documented by several studies, and our group found, in an earlier analysis, that decreasing particulate levels attenuate lung function decline in adults. OBJECTIVES: We investigated whether decreases in particulates with an aerodynamic diameter of less than 10 microm (PM10) were associated with lower rates of reporting respiratory symptoms (i.e., decreased morbidity) on follow-up. METHODS: The present analysis includes 7,019 subjects who underwent detailed baseline examinations in 1991 and a follow-up interview in 2002. Each subject was assigned model-based estimates of average PM10 during the 12 months preceding each health assessment and the difference was used as the exposure variable of interest (DeltaPM10). Analyses were stratified by symptom status at baseline and associations between DeltaPM10 and change in symptom status during follow-up were adjusted for important baseline characteristics, smoking status at follow-up, and season. We then estimated adjusted odds ratios for symptoms at follow-up and numbers of symptomatic cases prevented due to the observed reductions in PM10. MEASUREMENTS AND MAIN RESULTS: Residential exposure to PM10 was lower in 2002 than in 1991 (mean decline 6.2 microg/m3; SD = 3.9 microg/m3). Estimated benefits (per 10,000 persons) attributable to the observed changes in PM10-levels were: 259 (95% confidence interval [CI]: 102-416) fewer subjects with regular cough, 179 (95% CI, 30-328) fewer subjects with chronic cough or phlegm and 137 (95% CI, 9-266) fewer subjects with wheezing and breathlessness. CONCLUSIONS: Reductions in particle levels in Switzerland over the 11-year follow-up period had a beneficial effect on respiratory symptoms among adults.

[CME: Legionella pneumonia]. / CME: Legionellenpneumonie.

CME: Legionella pneumonia Abstract. Legionnaire's disease is a usually severe form of pneumonia caused by Legionella pneumophila, a Gram-negative bacterium with an airborne transmission. The infection is acquired in the community, but cases of hospital acquisition from hot water systems have been described. The most common clinical features are cough, fever, gastrointestinal symptoms, hyponatremia and altered liver function tests. The mainstay investigations to confirm diagnosis are urine antigen, sputum polymerase chain reaction, sputum or bronchial alveolar lavage cultures. Standard antibiotic treatment are macrolides or fluoroquinolones.

The independent association of source-specific transportation noise exposure, noise annoyance and noise sensitivity with health-related quality of life.

Noise exposure is affecting health-related quality of life (HRQoL). There are many modelling approaches linking specific noise sources with single health-related outcomes. However, an integrated approach is missing taking into account measured levels as well as noise annoyance and sensitivity and assessing their independent association with HRQoL domains. Therefore, we investigated the predictive association of most common transportation noise sources (aircraft, railway and road traffic) as well as transportation noise annoyance and noise sensitivity with HRQoL using data from SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults). We assessed 2035 subjects, who participated in the second and third wave of SAPALDIA (3&4) and had complete information on exposure, outcome and covariates. At SAPALDIA3, we calculated annual means (Lden) of source-specific transportation noise exposure at the most exposed facade of participant's dwelling floor height. Participants reported noise annoyance on the widely used 11-point ICBEN scale and answered to 10 questions assessing individual noise sensitivity. To assess the potentially predictive effect of these noise exposures, HRQoL was assessed about 8 years later (SAPALDIA4) using the SF-36. We performed predictive multiple quantile regression models to elucidate associations of noise parameters measured at SAPALDIA3 with median SF-36 scores at SAPALDIA4. Source-specific transportation noise exposures showed few yet not consistent associations with HRQoL scores. We observed statistically significant negative associations of transportation noise annoyance with HRQoL scores covering mental health components (adjusted difference in SF-36 mental health score between highest vs. lowest annoyance tertile: -2.54 (95%CI: -3.89; -1.20). Noise sensitivity showed strongest and most consistent associations with HRQoL scores covering both general and mental health components (adjusted difference in SF-36 scores between highest vs. lowest sensitivity tertile: Mental health -5.96 (-7.57; -4.36); general health -5.16 (-7.08; -3.24)). Within all noise parameters, we predominantly observed negative associations of noise sensitivity with HRQoL attaining a magnitude of potential clinical relevance. This implies that factors other than transportation noise exposure may be relevant for this exposure-outcome relation. Nonetheless, transportation noise annoyance showed relevant associations with mental health components, indicating a negative association of transportation noise with HRQoL.