Designing interactive visualizations for analyzing chronic lung diseases in a user-centered approach.

OBJECTIVES: Medical practitioners analyze numerous types of data, often using archaic representations that do not meet their needs. Pneumologists who analyze lung function exams must often consult multiple exam records manually, making comparisons cumbersome. Such shortcomings can be addressed with interactive visualizations, but these must be designed carefully with practitioners' needs in mind. MATERIALS AND METHODS: A workshop with experts was conducted to gather user requirements and common tasks. Based on the workshop results, we iteratively designed a web-based prototype, continuously consulting experts along the way. The resulting application was evaluated in a formative study via expert interviews with 3 medical practitioners. RESULTS: Participants in our study were able to solve all tasks in accordance with experts' expectations and generally viewed our system positively, though there were some usability and utility issues in the initial prototype. An improved version of our system solves these issues and includes additional customization functionalities. DISCUSSION: The study results showed that participants were able to use our system effectively to solve domain-relevant tasks, even though some shortcomings could be observed. Using a different framework with more fine-grained control over interactions and visual elements, we implemented design changes in an improved version of our prototype that needs to be evaluated in future work. CONCLUSION: Employing a user-centered design approach, we developed a visual analytics system for lung function data that allows medical practitioners to more easily analyze the progression of several key parameters over time.

[Diagnosis and therapy of patients with asthma in Germany. Results of the care study RELEVANT]. / Diagnostik und Therapie von Patienten mit Asthma in Deutschland : Ergebnisse der Versorgungsstudie RELEVANT.

BACKGROUND: Diagnostic and therapeutic options for asthma have improved with asthma control and remission being of central importance. The RELEVANT study aimed for a nationwide snapshot of current asthma diagnosis and treatment in general practice and specialty care for identification of further aspects for optimization. METHOD: RELEVANT is a nationwide cross-sectional study using a structured questionnaire. This comprised 14 questions on asthma-related topics covering diagnostics and therapy. Participants were general practitioners/internal medicine specialists and pulmonologists. RESULTS: A total of 1,558 persons took part in the survey. Regarding relevant specific diagnostic procedures for asthma, GPs/internists almost exclusively mentioned pulse oximetry. Among the pulmonologists, fractional exhaled nitric oxide (FeNO) measurement was mentioned, among others. FeNO and blood eosinophils were only mentioned by the pulmonologists as diagnostic and treatment-relevant markers. A total of more than 60% of the GPs/internists surveyed stated that only around 25% or fewer of their patients would voluntarily report restrictions in their everyday lives. Regarding drug treatment, the majority stated that they recognized differences between various ICS/LABA combination therapies. CONCLUSIONS: The results indicate a need for optimization, particularly regarding asthma control. This involves both a better assessment by patients' everyday life restrictions and modern ways of assessing asthma control in cooperation between GPs/internal medicine specialists and pulmonologists. One fifth of respondents do not see any differences between various ICS/LABA combinations in daily practice, although there are pharmacodynamic and pharmacokinetic differences.

ERS International Congress 2023: highlights from the Airway Diseases Assembly.

In this review, early career and senior members of Assembly 5 (Airway Diseases, Asthma, COPD and Chronic Cough) present key recent findings pertinent to airway diseases that were presented during the European Respiratory Society International Congress 2023 in Milan, Italy, with a particular focus on asthma, COPD, chronic cough and bronchiectasis. During the congress, an increased number of symposia, workshops and abstract presentations were organised. In total, 739 abstracts were submitted for Assembly 5 and the majority of these were presented by early career members. These data highlight the increased interest in this group of respiratory diseases.

Impact of Heated Tobacco Products, E-Cigarettes, and Combustible Cigarettes on Small Airways and Arterial Stiffness.

Smoking cessation is difficult but maintaining smoke-free without nicotine replacement therapy is even harder. During the last few years, several different alternative products, including heated tobacco products (HTP), have been introduced to the market. In this study, we investigated the acute effects of IQOSTM and gloTM (two HTP) consumption on small airway function and arterial stiffness in a head-to-head design, comparing them to combustible cigarettes, nicotine-free e-cigarettes and a sham smoking group. Seventeen healthy occasional smokers were included in a single-center, five-arm, crossover study. The parameters of small airway function and hemodynamics were collected at several time points before and after consumption using Mobil-O-Graph™ (I.E.M., Stolberg, Germany) and TremoFlo® c-100 (THORASYS Thoracic Medical Systems Inc., Montreal, QC, Canada). Small airway obstruction and resistance were both significantly increased after the consumption of cigarettes and substitute products. All products containing nicotine led to similar significant increases in blood pressure and arterial stiffness. Hemodynamic parameters were also increased after the consumption of e-cigarettes without nicotine, but compared to nicotine-containing products, the increase was shorter and weaker. We conclude that, although it has yet to be determined why, HTP have acute harmful effects on small airway function, possibly even exceeding the effects of combustible cigarettes. Like other nicotine-containing products, HTP leads to a nicotine-related acute increase in arterial stiffness and cardiovascular stress, similar to combustible cigarettes, which associates these products with an increased cardiovascular risk.

Costs of Weaning Failure: A Prospective, Multicentre, Controlled, Non-Randomised, Interventional Study on Economic Implications for the German Health Care System.

BACKGROUND: Intensive care patients with respiratory failure often need invasive mechanical ventilation (IMV). With increasing population age and multimorbidity, the number of patients who cannot be weaned from IMV rises as well. Up to 85% of these patients have no access to a certified weaning centre. Their medical care is associated with impaired quality of life and high costs for the German health care system. OBJECTIVES: This study examined the weaning outcome of patients in certified weaning centres after a primarily unsuccessful weaning attempt in order to calculate saving expenses compared to patients on long-term IMV in an outpatient setting. METHODS: In this multicentre, controlled, non-randomised, interventional, prospective study, 61 patients (16 from out-of-hospital long-term IMV, 49 from other hospitals) were referred to a certified weaning centre for a second weaning phase. The incurred costs after 1 year of the latter were compared to insurance claim data of patients who were discharged from an acute hospital stay to receive IMV in an outpatient setting. RESULTS: In the intervention group, 50 patients (82%) could be completely weaned or partially weaned using non-invasive ventilation, thus not needing IMV any longer. The costs per patient for weaning and out-of-hospital care in the intervention group were EUR 114,877.08, and the costs in the comparison cohort were EUR 234,442.62. CONCLUSIONS: Early transfer to a certified weaning centre can increase weaning success and reduce total costs by approximately EUR 120,000 per patient in the first year. Given the existing structural prerequisites in Germany, every patient should have access to a weaning centre before being transferred to long-term IMV, from a medical and health economical point of view.

Minimal clinically important difference for impulse oscillometry in adults with asthma.

BACKGROUND: Impulse oscillometry (IOS) allows an effort-independent evaluation of small airway function in asthma. Unfortunately, well-determined minimal clinically important differences (MCIDs) for IOS measures are lacking. Here, we provide MCIDs for frequently used IOS measures, namely frequency dependence of resistance (FDR) and area of reactance (AX), in patients with asthma. METHODS: We performed IOS at baseline and 1 year later in adult patients with mild-to-severe asthma (n=235). In a two-step approach, we first applied a distribution-based method to statistically determine the MCID. Next, we validated the proposed MCID according to patient-reported outcome measures (PROMs): Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Questionnaire-7 (ACQ-7) and Asthma Control Test (ACT). We used multivariable analyses to investigate the proposed MCIDs as predictors for improvements in PROMs compared with the established MCID of forced expiratory volume in 1 s (FEV1). RESULTS: The proposed MCID was a decline of ≥0.06 kPa·L-1·s-1 and ≥0.65 kPa·L-1 for FDR and AX, respectively. Patients who had changes beyond the MCIDs for both FDR and AX showed greater improvements in all PROMs than those who had not. The mean improvements in PROMs were beyond the established MCIDs for ACQ-7 and AQLQ, and approximated the MCID for ACT. Multivariable analyses demonstrated the MCIDs for both FDR and AX as independent predictors for the MCIDs of all PROMs. The MCID for FDR was a stronger predictor of all PROMs than the MCID for FEV1. CONCLUSIONS: This study provides MCIDs for IOS-derived measures in adult patients with asthma and emphasises that small airway function is a distinguished end-point beyond the conventional measure of FEV1.

Impact of Chewing Bags, E-Cigarettes, and Combustible Cigarettes on Arterial Stiffness and Small Airway Function in Healthy Students.

Several substitute products are discussed as a healthier alternative to smoking, thereunder e-cigarettes and smokeless tobacco products, e.g., chewing bags, which are increasingly used in this context. We investigated the acute effects of chewing bags compared to combustible cigarettes and e-cigarettes with and without nicotine on small airways and arterial stiffness in a head-to-head design. This single-center, four-arm cross-overstudy included 20 healthy occasional smokers (25 ± 0.6 years). On four test days, participants consumed one product per day. Before, during, and after consumption, peripheral and central hemodynamic as well as arterial stiffness parameters were measured by Mobil-O-Graph™ (I.E.M., Germany). Resistance and small airway function were assessed by tremoFlo® c-100 (THORASYS Thoracic Medical Systems Inc.). The combustible cigarette and the e-cigarettes with and without nicotine significantly increased the resistance of the small airways (p < 0.05), while chewing bags had no effect. All nicotine containing products (e-cigarette with nicotine, combustible cigarette, chewing bag) as well as the e-cigarette without nicotine significantly increased parameters of hemodynamic and arterial stiffness. Changes in blood pressure and arterial stiffness were similar after smoking, vaping, and using chewing bags. We conclude that e-cigarettes and combustible cigarettes have similar acute harmful effects on small airway dysfunction. All nicotine containing products are associated with an increased cardiovascular risk compared with no product use.

Gender-specific differences in COPD symptoms and their impact for the diagnosis of cardiac comorbidities.

BACKGROUND: In chronic obstructive pulmonary disease (COPD), gender-specific differences in the prevalence of symptoms and comorbidity are known. RESEARCH QUESTION: We studied whether the relationship between these characteristics depended on gender and carried diagnostic information regarding cardiac comorbidities. STUDY DESIGN AND METHODS: The analysis was based on 2046 patients (GOLD grades 1-4, 795 women; 38.8%) from the COSYCONET COPD cohort. Assessments comprised the determination of clinical history, comorbidities, lung function, COPD Assessment Test (CAT) and modified Medical Research Council dyspnea scale (mMRC). Using multivariate regression analyses, gender-specific differences in the relationship between symptoms, single CAT items, comorbidities and functional alterations were determined. To reveal the relationship to cardiac disease (myocardial infarction, or heart failure, or coronary artery disease) logistic regression analysis was performed separately in men and women. RESULTS: Most functional parameters and comorbidities, as well as CAT items 1 (cough), 2 (phlegm) and 5 (activities), differed significantly (p < 0.05) between men and women. Beyond this, the relationship between functional parameters and comorbidities versus symptoms showed gender-specific differences, especially for single CAT items. In men, item 8 (energy), mMRC, smoking status, BMI, age and spirometric lung function was related to cardiac disease, while in women primarily age was predictive. INTERPRETATION: Gender-specific differences in COPD not only comprised differences in symptoms, comorbidities and functional alterations, but also differences in their mutual relationships. This was reflected in different determinants linked to cardiac disease, thereby indicating that simple diagnostic information might be used differently in men and women. CLINICAL TRIAL REGISTRATION: The cohort study is registered on ClinicalTrials.gov with identifier NCT01245933 and on GermanCTR.de with identifier DRKS00000284, date of registration November 23, 2010. Further information can be obtained on the website http://www.asconet.net .

Effectiveness of Extrafine Single Inhaler Triple Therapy in Chronic Obstructive Pulmonary Disease (COPD) in Germany - The TriOptimize Study.

Purpose: Real-word evidence on the effectiveness of switching from dual therapies or triple therapies (multiple inhalers) to extrafine single-inhaler triple therapy (efSITT), which consists of the inhaled corticosteroid (ICS) beclomethasone, the long-acting ß2-agonist (LABA) formoterol and the long-acting muscarinic antagonist (LAMA) glycopyrronium, in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) is limited. The impact of switching to efSITT on health-related quality of life (HRQoL), COPD specific symptoms, lung function and treatment adherence were assessed in routine clinical care. Patients and Methods: Patients were recruited at 148 sites in Germany between 2017 and 2020 in this multicenter, non-interventional observational study. Demographics, clinical data and treatment history were collected at baseline. HRQoL (measured by COPD Assessment Test [CAT]), lung function and adherence (measured by Test of Adherence to Inhalers [TAI]) were assessed at baseline and after six months. Descriptive analyses were conducted by prior treatment and GOLD groups as well as for the overall population. Results: 55.1% of the 2623 included patients were male. Mean age was 65.8 years. 57.5% of the patients were previously treated with ICS+LABA+LAMA (multiple inhalers), 23.9% with ICS/LABA (single or two inhalers) and 18.6% with LAMA/LABA (single or two inhalers). After six months, largest mean improvements in the total CAT score were observed in the ICS/LABA (-3.9) and LAMA/LABA (-3.9) prior treatment groups as well as in patients in GOLD group B (-2.9). In the overall population, the CAT items for cough, phlegm, and dyspnea decreased on average by -0.4 points each. After six months, FEV1 increased by 2.0 percentage points in relation to predicted values. The percentages of measured sRtot and RV of predicted values decreased by 24.5 and 4.4 percentage points, respectively. The percentage of patients with good adherence increased from 67.8% to 76.5%. Conclusion: Treatment switch to efSITT resulted in an improvement of HRQoL, COPD specific symptoms, lung function parameters and adherence under real-world conditions.

Investigation of tracer gas transport in a new numerical model of lung acini.

Obstructive pulmonary diseases are associated with considerable morbidity. For an early diagnosis of these diseases, inert gas washouts can potentially be used. However, the complex interaction between lung anatomy and gas transport mechanisms complicates data analysis. In order to investigate this interaction, a numerical model, based on the finite difference method, consisting of two lung units connected in parallel, was developed to simulate the tracer gas transport within the human acinus. Firstly, the geometries of the units were varied and the diffusion coefficients (D) were kept constant. Secondly, D was changed and the geometry was kept constant. Furthermore, simple monoexponential growth functions were applied to evaluate the simulated data. In 109 of the 112 analyzed curves, monoexponential function matched simulated data with an accuracy of over 90%, potentially representing a suitable numerical tool to predict transport processes in further model extensions. For total flows greater than 5 × 10-4 ml/s, the exponential growth constants increased linearly with linear increasing flow to an accuracy of over 95%. The slopes of these linear trend lines of 1.23 µl-1 (D = 0.6 cm2/s), 1.69 µl-1 (D = 0.3 cm2/s), and 2.25 µl-1 (D = 0.1 cm2/s) indicated that gases with low D are more sensitive to changes in flows than gases with high D.

Changes of breath volatile organic compounds in healthy volunteers following segmental and inhalation endotoxin challenge.

It is still unclear how airway inflammation affects the breath volatile organic compounds (VOCs) profile in exhaled air. We therefore analyzed breath following well-defined pulmonary endotoxin (lipopolysaccharide, LPS) challenges. Breath was collected from ten healthy non-smoking subjects at eight time points before and after segmental and whole lung LPS inhalation challenge. Four Tenax-TA® adsorption tubes were simultaneously loaded from an aluminum reservoir cylinder and independently analyzed by two research groups using gas chromatography-mass spectrometry. Airway inflammation was assessed in bronchoalveolar lavage (BAL) and in sputum after segmental and inhaled LPS challenge, respectively. Segmental LPS challenge significantly increased the median (interquartile range, IQR) percentage of neutrophils in BAL from 3.0 (4.2) % to 64.0 (7.3) %. The inhalation challenge increased sputum neutrophils from 33.9 (26.8) % to 78.3 (13.5) %. We observed increases in breath aldehydes at both time points after segmental and inhaled LPS challenge. These results were confirmed by an independent laboratory. The longitudinal breath analysis also revealed distinct VOC patterns related to environmental exposures, clinical procedures, and to metabolic changes after food intake. Changes in breath aldehydes suggest a relationship to LPS induced inflammation compatible with lipid peroxidation processes within the lung. Findings from our longitudinal data highlight the need for future studies to better consider the potential impact of the multiple VOCs from detergents, hygiene or lifestyle products a subject is continuously exposed to. We suspect that this very individual 'owncloud' exposure is contributing to an increased variability of breath aldehydes, which might limit a use as inflammatory markers in daily clinical practice.

Longitudinal Impact of Sputum Inflammatory Phenotypes on Small Airway Dysfunction and Disease Outcomes in Asthma.

BACKGROUND: Little is known about the relationship between airway inflammatory phenotypes and some important asthma features such as small airway dysfunction (SAD). OBJECTIVE: To describe the longitudinal impact of airway inflammatory phenotypes on SAD and asthma outcomes. METHODS: We measured eosinophil and neutrophil counts in induced sputum at baseline and 1 year later to stratify 197 adult patients with asthma into 4 inflammatory phenotypes. We conducted a comprehensive assessment of lung function using spirometry, body plethysmography, impulse oscillometry, and inert gas single and multiple breath washouts. We compared lung function, asthma severity, exacerbation frequency, and symptom control between the phenotypes. We studied the longitudinal impact of persistent sputum inflammatory phenotypes and the change of sputum cell counts on lung function. RESULTS: Patients were stratified into eosinophilic (23%, n = 45), neutrophilic (33%, n = 62), mixed granulocytic (22%, n = 43), and paucigranulocytic (24%, n = 47) phenotypes. Patients with eosinophilic and mixed granulocytic asthma had higher rates of airflow obstruction and severe exacerbation as well as poorer symptom control than patients with paucigranulocytic asthma. All SAD measures were worse in patients with eosinophilic and mixed asthma than in those with paucigranulocytic asthma (all P values <.05). Eosinophilic asthma also indicated worse distal airflow obstruction, increased ventilation inhomogeneity (all P values <.05), and higher tendency for severe exacerbation (P = .07) than neutrophilic asthma. Longitudinally, persistent mixed granulocytic asthma was associated with the worst follow-up measures of SAD compared with persistent neutrophilic, persistent paucigranulocytic, or nonpersistent asthma phenotypes. In patients with stable forced expiratory volume in 1 second (FEV1), the mean increase in small airway resistance (R5-20) was greater in patients with persistent mixed granulocytic asthma (+103%) than in patients with persistent neutrophilic (+26%), P = .040, or persistent paucigranulocytic asthma (-41%), P = .028. Multivariate models adjusted for confounders and treatment with inhaled or oral corticosteroids or antieosinophilic biologics indicated that the change of sputum eosinophil rather than neutrophil counts is an independent predictor for the longitudinal change in FEV1, forced expiratory flow at 25% to 75% of forced vital capacity, specific effective airway resistance, residual lung volume, and lung clearance index. CONCLUSIONS: In asthma, airway eosinophilic inflammation is the main driver of lung function impairment and poor disease outcomes, which might also be aggravated by the coexistence of airway neutrophilia to confer a severe mixed granulocytic asthma phenotype. Persistent airway eosinophilia might be associated with dynamic SAD even in patients with stable FEV1.

Clinical characterization of a novel alpha1-antitrypsin null variant: PiQ0Heidelberg.

The clinical characterization of a null variant of SERPINA1 - PiQ0Heidelberg - resulting in alpha1-antitrypsin (AAT) deficiency is described. This rare mutation (c.-5+5 G > A) has been previously identified but not clinically described. The 77 year-old female patient had GOLD-3, Group B COPD, severe destructive panlobular emphysema and newly observed respiratory failure on exertion at the time the genetic analysis was performed. Serum AAT level was 0.1 g/L (reference 0.9-2.0 g/L). Isoelectric focusing showed only the Z-protein indicating that this was a null mutation. The patient has started AAT replacement. Early screening and identification of AAT deficiency would allow for earlier intervention.

Case Series: Convalescent Plasma Therapy for Patients with COVID-19 and Primary Antibody Deficiency.

Patients with primary antibody deficiency are at risk for severe and in many cases for prolonged COVID-19. Convalescent plasma treatment of immunocompromised individuals could be an option especially in countries with limited access to monoclonal antibody therapies. While studies in immunocompetent COVID19 patients have demonstrated only a limited benefit, evidence for the safety, timing, and effectiveness of this treatment in antibody-deficient patients is lacking. Here, we describe 16 cases with primary antibody deficiency treated with convalescent plasma in four medical centers. In our cohort, treatment was associated with a reduction in viral load and improvement of clinical symptoms, even when applied over a week after onset of infection. There were no relevant side effects besides a short-term fever reaction in one patient. Longitudinal full-genome sequencing revealed the emergence of mutations in the viral genome, potentially conferring an antibody escape in one patient with persistent viral RNA shedding upon plasma treatment. However, he resolved the infection after a second course of plasma treatment. Thus, our data suggest a therapeutic benefit of convalescent plasma treatment in patients with primary antibody deficiency even months after infection. While it appears to be safe, PCR follow-up for SARS-CoV-2 is advisable and early re-treatment might be considered in patients with persistent viral shedding.