Nation-wide hospitalization databases include diagnostic information at the level of an entire population over an extended period of time. Comorbidity network and early disease development can be ...unveiled. Chronic obstructive pulmonary disease (COPD) is an underdiagnosed condition for which it is crucial to identify early disease indicators. The identification of gender-specific conditions preceding the onset of COPD may reveal disease progression patterns allowing for early diagnosis and intervention. The objective of the study was to investigate the antecedent hospitalization history of patients newly diagnosed with COPD and to retrace a gender-specific trajectory of coded entities prior to the onset of COPD.
A population-wide hospitalization database including information about all hospitalizations in Switzerland between 2002 and 2018 was used. COPD cases were extracted from the database and comorbidities occurring prior to the onset of COPD identified. Comorbidities significantly over-represented in COPD compared with a 1:1, age- and sex-matched control population were identified and their longitudinal evolution was analyzed.
Between 2002 and 2018, 697,714 hospitalizations with coded COPD were recorded in Switzerland. Sixty-two diagnoses were significantly over-represented before onset of COPD. These preceding comorbidities included both well-established conditions and novel links to COPD. Early pre-conditions included nicotine and alcohol abuse, obesity and cardiovascular diseases. Later comorbidities included atrial fibrillation, diseases of the genitourinary system and pneumonia. Atherosclerotic heart diseases were more prevalent in males, whereas hypothyroidism, varicose and intestinal disorders were more frequent in females. Disease trajectories were validated using an independent data set.
Gender-specific disease trajectories highlight early indicators and pathogenetic links between COPD and antecedent diseases and could allow for early detection and intervention.
Nonlinear regression models are applied in a broad variety of scientific fields. Various R functions are already dedicated to fitting such models, among which the function nls() has a prominent ...position. Unlike linear regression fitting of nonlinear models relies on non-trivial assumptions and therefore users are required to carefully ensure and validate the entire modeling. Parameter estimation is carried out using some variant of the least- squares criterion involving an iterative process that ideally leads to the determination of the optimal parameter estimates. Therefore, users need to have a clear understanding of the model and its parameterization in the context of the application and data considered, an a priori idea about plausible values for parameter estimates, knowledge of model diagnostics procedures available for checking crucial assumptions, and, finally, an under- standing of the limitations in the validity of the underlying hypotheses of the fitted model and its implication for the precision of parameter estimates. Current nonlinear regression modules lack dedicated diagnostic functionality. So there is a need to provide users with an extended toolbox of functions enabling a careful evaluation of nonlinear regression fits. To this end, we introduce a unified diagnostic framework with the R package nlstools. In this paper, the various features of the package are presented and exemplified using a worked example from pulmonary medicine.
Sleep apnea (SA) is a prevalent disorder characterized by recurrent events of nocturnal apnea originating from obstructive and/or central mechanisms. SA disrupts normal sleep and can lead to a series ...of complications when left untreated. SA results in intermittent hypoxia which has an impact on the cardio- and cerebrovascular system. Hospitalized patients with SA typically have a greater burden of comorbidity, a longer length of hospital stay, but may show an improvement of in-hospital mortality compared to patients without diagnosed SA. The reason for this survival benefit is controversial and we aimed to clarify this protective effect in the light of predictive factors including SA-associated comorbidities using a nation-wide hospitalization database. Data were extracted from a nation-wide hospitalization database provided by the Swiss Federal Office for Statistics. Hospitalized patients with a SA co-diagnosis were extracted from the database together with a 1:1-matched control population without SA. Overall, 212'581 patients with SA were hospitalized in Switzerland between 2002 and 2018. Compared to the controls, SA cases had a longer median length of hospital stay (7 days; 95% CI: 3 to 15 vs. 4 days; 95% CI: 2 to 10) (p < 0.001) and a higher median number of comorbidities (8 comorbidities; IQR: 5 to 11 vs. 3 comorbidities; IQR: 1 to 6) (p < 0.001). The risk of in-hospital mortality was lower in the SA cases compared to the controls (OR: 0.73; 95% CI: 0.7 to 0.76; p < 0.001). SA was associated with a survival benefit in hospitalizations related to 28 of 47 conditions with the highest rate of in-hospital death. Sixty-three comorbidities were significantly over-represented in SA cases among which obesity, hypertension and anatomic nasal deviations were associated with a significant decrease of in-hospital mortality. Compared to matched controls, SA was associated with significant and relevant inpatient survival benefit in a number of most deadly conditions. Within SA-patients, associated comorbidities mostly correlated with a poorer prognosis, whereas obesity and hypertension were associated with an improved in-hospital mortality.
The infectious coronavirus disease 2019 (COVID-19) pandemic is an ongoing global healthcare challenge. Up to one-third of hospitalised patients develop severe pulmonary complications and acute ...respiratory distress syndrome. Pulmonary outcomes following COVID-19 are unknown.
The Swiss COVID-19 lung study is a multicentre prospective cohort investigating pulmonary sequelae of COVID-19. We report on initial follow-up 4 months after mild/moderate or severe/critical COVID-19 according to the World Health Organization severity classification.
113 COVID-19 survivors were included (mild/moderate n=47, severe/critical n=66). We confirmed several comorbidities as risk factors for severe/critical disease. Severe/critical disease was associated with impaired pulmonary function,
diffusing capacity of the lung for carbon monoxide (
) % predicted, reduced 6-min walk distance (6MWD) and exercise-induced oxygen desaturation. After adjustment for potential confounding by age, sex and body mass index (BMI), patients after severe/critical COVID-19 had a
20.9% pred (95% CI 12.4-29.4% pred, p=0.01) lower at follow-up.
% pred was the strongest independent factor associated with previous severe/critical disease when age, sex, BMI, 6MWD and minimal peripheral oxygen saturation at exercise were included in the multivariable model (adjusted odds ratio per 10% predicted 0.59, 95% CI 0. 37-0.87; p=0.01). Mosaic hypoattenuation on chest computed tomography at follow-up was significantly associated with previous severe/critical COVID-19 including adjustment for age and sex (adjusted OR 11.7, 95% CI 1.7-239; p=0.03).
4 months after severe acute respiratory syndrome coronavirus 2 infection, severe/critical COVID-19 was associated with significant functional and radiological abnormalities, potentially due to small-airway and lung parenchymal disease. A systematic follow-up for survivors needs to be evaluated to optimise care for patients recovering from COVID-19.
The objectives of the present study were to evaluate the discriminating power of spirometric and plethysmographic lung function parameters to differenciate the diagnosis of asthma, ACO, COPD, and to ...define functional characteristics for more precise classification of obstructive lung diseases. From the databases of 4 centers, a total of 756 lung function tests (194 healthy subjects, 175 with asthma, 71 with ACO, 78 with COPD and 238 with CF) were collected, and gradients among combinations of target parameters from spirometry (forced expiratory volume one second: FEV1; FEV1/forced vital capacity: FEV1/FVC; forced expiratory flow between 25-75% FVC: FEF25-75), and plethysmography (effective, resistive airway resistance: sReff; aerodynamic work of breathing at rest: sWOB), separately for in- and expiration (sReffIN, sReffEX, sWOBin, sWOBex) as well as static lung volumes (total lung capacity: TLC; functional residual capacity: FRCpleth; residual volume: RV), the control of breathing (mouth occlusion pressure: P0.1; mean inspiratory flow: VT/TI; the inspiratory to total time ratio: TI/Ttot) and the inspiratory impedance (Zinpleth = P0.1/VT/TI) were explored. Linear discriminant analyses (LDA) were applied to identify discriminant functions and classification rules using recursive partitioning decision trees. LDA showed a high classification accuracy (sensitivity and specificity > 90%) for healthy subjects, COPD and CF. The accuracy dropped for asthma (~70%) and even more for ACO (~60%). The decision tree revealed that P0.1, sRtot, and VT/TI differentiate most between healthy and asthma (68.9%), COPD (82.1%), and CF (60.6%). Moreover, using sWOBex and Zinpleth ACO can be discriminated from asthma and COPD (60%). Thus, the functional complexity of obstructive lung diseases can be understood, if specific spirometric and plethysmographic parameters are used. Moreover, the newly described parameters of airway dynamics and the central control of breathing including Zinpleth may well serve as promising functional marker in the field of precision medicine.
Sarcoidosis is a multisystem disease with an unpredictable and sometimes fatal course while the underlying pathomechanism is still unclear. Reasons of the increasing hospitalization rate and ...mortality in the United States remain in dispute but incriminated are a number of distinct comorbidities and risk factors as well as the application of more aggressive therapeutic agents. Studies reflecting the recent development in central Europe are lacking. Our aim was to investigate the recent mortality and hospitalization rates as well as the underlying comorbidities of hospitalized sarcoidosis patients in Switzerland. In this longitudinal, nested case-control study, a nation-wide database provided by the Swiss Federal Office for Statistics enclosing every hospital entry covering the years 2002-2012 (n = 15,627,573) was analyzed. There were 8,385 cases with a diagnosis of sarcoidosis representing 0.054% (8,385 / 15,627,573) of all hospitalizations in Switzerland. These cases were compared with age- and sex-matched controls without the diagnosis of sarcoidosis. Hospitalization and mortality rates in Switzerland remained stable over the observed time period. Comorbidity analysis revealed that sarcoidosis patients had significantly higher medication-related comorbidities compared to matched controls, probably due to systemic corticosteroids and immunosuppressive therapy. Sarcoidosis patients were also more frequently re-hospitalized (median annual hospitalization rate 0.28 IQR 0.15-0.65 vs. 0.19 IQR 0.13-0.36 per year; p < 0.001), had a longer hospital stay (6 IQR 2-13 vs. 4 IQR 1-8 days; p < 0.001), had more comorbidities (4 IQR 2-7 vs. 2 IQR 1-5; p < 0.001), and had a significantly higher in-hospital mortality (2.6% 95% CI 2.3%-2.9% vs. 1.8% 95% CI 1.5%-2.1% (p < 0.001). A worse outcome was observed among sarcoidosis patients having co-occurrence of associated respiratory diseases. Moreover, age was an important risk factor for re-hospitalization.
Cancer immunotherapy outcomes are shaped by various soft variables including diet/microbiome, physical activity, and circadian rhythms. This commentary advocates a holistic framework for cancer ...immunotherapy to enhance treatment response and improve quality of life.
Cystic fibrosis (CF) is a life-threatening genetic disorder, characterized by chronic microbial lung infections due to abnormally viscous mucus secretions within airways. The clinical management of ...CF typically involves regular respiratory-tract cultures in order to identify pathogens and to guide treatment. However, culture-based methods can miss atypical or slow-growing microbes. Furthermore, the isolated microbes are often not classified at the strain level due to limited taxonomic resolution.
Here, we show that untargeted metagenomic sequencing of sputum DNA can provide valuable information beyond the possibilities of culture-based diagnosis. We sequenced the sputum of six CF patients and eleven control samples (including healthy subjects and chronic obstructive pulmonary disease patients) without prior depletion of human DNA or cell size selection, thus obtaining the most unbiased and comprehensive characterization of CF respiratory tract microbes to date. We present detailed descriptions of the CF and healthy lung microbiome, reconstruct near complete pathogen genomes, and confirm that the CF lungs consistently exhibit reduced microbial diversity. Crucially, the obtained genomic sequences enabled a detailed identification of the exact pathogen strain types, when analyzed in conjunction with existing multi-locus sequence typing databases. We also detected putative pathogenicity islands and indicators of antibiotic resistance, in good agreement with independent clinical tests.
Unbiased sputum metagenomics provides an in-depth profile of the lung pathogen microbiome, which is complementary to and more detailed than standard culture-based reporting. Furthermore, functional and taxonomic features of the dominant pathogens, including antibiotics resistances, can be deduced-supporting accurate and non-invasive clinical diagnosis.
COPD is associated with a relevant burden of disease and a high mortality worldwide. Only recently, the importance of comorbidities of COPD has been recognized. Studies postulated an association with ...inflammatory conditions potentially sharing pathogenic pathways and worsening overall prognosis. More evidence is required to estimate the role of comorbidities of COPD. Our aim was to investigate the prevalence and clustering of comorbidities associated with COPD, and to estimate their impact on clinically relevant outcomes. In this population-based case-control study, a nation-wide database provided by the Swiss Federal Office for Statistics enclosing every hospital entry covering the years 2002-2010 (n = 12'888'075) was analyzed using MySQL and R statistical software. Statistical methods included non-parametric hypothesis testing by means of Fisher's exact test and Wilcoxon rank sum test, as well as linear models with generalized estimating equation to account for intra-patient variability. Exploratory multivariate approaches were also used for the identification of clusters of comorbidities in COPD patients. In 2.6% (6.3% in patients aged >70 years) of all hospitalization cases an active diagnosis of COPD was recorded. In 21% of these cases, COPD was the main reason for hospitalization. Patients with a diagnosis of COPD had more comorbidities (7 IQR 4-9 vs. 3 IQR 1-6; Formula: see text), were more frequently rehospitalized (annual hospitalization rate 0.33 IQR 0.20-0.67 vs. 0.25 IQR 0.14-0.43/year; Formula: see text), had a longer hospital stay (9 IQR 4-15 vs. 5 IQR 2-11 days; Formula: see text), and had higher in-hospital mortality (5.9% 95% CI 5.8%-5.9% vs. 3.4% 95% CI 3.3%-3.5%; Formula: see text) compared to matched controls. A set of comorbidities was associated with worse outcome. We could identify COPD-related clusters of COPD-comorbidities.
•The disease modification concept is arbitrary.•The level of therapeutic causality cannot be objectified.•There is a continuum of treatment and disease outcomes.•Biomarkers are required as actionable ...tools for treatment personalization.
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