Numerical Algorithms For Analysis Of Dynamics Of Ideal Fluid With Free/moving Boundaries

This thesis proposes and examines various algorithms for analysis of steady ideal fluid capillary flows with free/moving boundary.;For this class of problems, the leading parameter is the capillary number C which for an established flow and fixed geometry of the solution domain is proportional to the ratio of a velocity scale and surface tension. When C {dollar}\ll{dollar} 1 the problem can be simplified and is solved using Small Deformation Theory (SDT). Conditions for validity of SDT are identified.;When C = 0(1) one has to seek a simultaneous solution for two dependent variables, i.e. a flow field and a free surface shape. Depending on the order of linearization of the governing equations one arrives at the Picard Algorithm (linearization of the first order) and the 1-Step Algorithm (of the second order). The latter one provides significantly faster convergence.;All algorithms are based on a finite-difference approximation and the Alternate Direction Implicite (ADI) scheme has been chosen as a method of solution. A thorough study of an algebraic stability of equations of the flow field and the free surface, has been carried out. This is supplemented by an analytical and numerical analysis of existence and uniqueness of the solutions to the free surface equation. The Wachspress optimization of relaxation parameters has been used in order to accelerate convergence of the ADI.;Finite differences discretization implemented in the thesis is based on the Hermitian equations, which generated compact difference schemes of the second and higher order accuracy. In the thesis one can find a rigorous study of the interrelationship between the order of differencing scheme and the rate of convergence of the computed results with grid refining. This rate, called \u27grid-convergence order\u27 has been used as the criterion for identification of the minimum dimensionality of the computational grid. It was found that higher order methods require much finer grids than second order methods, to provide desired grid-convergence order.;For higher order method, the new fourth order compact difference estimate (independent of coordinate direction) of a mixed derivative was found. Its application significantly improved the grid-convergence order.;The discussion of the algorithms is supplemented by a physical interpretation of the results obtained for a number of particular cases

Subphenotypes of nonsteroidal antiinflammatory diseaseexacerbated respiratory disease identified by latent class analysis

Background Induced sputum (IS) allows to measure mediators of asthmatic inflammation in bronchial secretions. NSAID‐exacerbated respiratory disease (NERD) is recognized as a distinct asthma phenotype, usually with a severe course, eosinophilic airway inflammation, and increased production of pro‐inflammatory eicosanoids. A more insightful analysis of NERD patients has shown this phenotype to be nonhomogeneous. Objective We aimed to identify possible subphenotypes in a cohort of NERD patients with the means of latent class analysis (LCA). Methods A total of 95 asthma patients with aspirin hypersensitivity underwent sputum induction. High‐performance liquid chromatography or gas chromatography coupled with mass spectrometry was used to profile eicosanoids in induced sputum supernatant (ISS). Sixteen variables covering clinical characteristics, IS inflammatory cells, and eicosanoids were considered in the LCA. Results Three classes (subphenotypes) were distinguished within the NERD cohort. Class 1 subjects had mild‐to‐moderate asthma, an almost equal distribution of inflammatory cell patterns, the lowest concentrations of eicosanoids, and logLTE4/logPGE2 ratio. Class 2 represented severe asthma with impaired lung function despite high doses of steroids. High sputum eosinophilia was in line with higher pro‐inflammatory LTE4 in ISS and the highest logLTE4/logPGE2 ratio. Class 3 subjects had mild‐to‐moderate asthma and were also characterized by eosinophilic airway inflammation, yet increased production of pro‐ (LTE4, PGD2 and 11‐dehydro‐TBX2) was balanced by anti‐inflammatory PGE2. The value of logLTE4/logPGE2 was between values calculated for classes 1 and 3, similarly to disease control and severity. Conclusions LCA revealed three distinct NERD subphenotypes. Our results support a more complex pathobiology of aspirin hypersensitivity. Considering NERD heterogeneity, the relationship between inflammatory pathways and clinical manifestations of asthma may lead to more individualized treatment in difficult to treat patients in the future

Validation of the Polish-language version of the COPD Assessment Test

INTRODUCTION The COPD Assessment Test (CAT) is a standardized patient–completed tool dedicated to assessment of symptom severity. While the Polish CAT version has been used for a few years, it has not been validated so far. OBJECTIVES The aim of the study was to validate the Polish‑language version of the CAT questionnaire by assessing its reproducibility and reliability. PATIENTS AND METHODS Validation of the Polish‑language version of the CAT questionnaire was a substudy of the international multicenter observational cross‑sectional POPE survey of patients with chronic obstructive pulmonary disease (COPD) in Central and Eastern European countries. The study was completed in 395 outpatients with stable disease at least 4 weeks before the survey. Validation was performed with the use of the Spearman correlation and Cronbach α coefficients, Cohen κ test, and the Bland–Altman procedure. RESULTS The internal consistency assessed by the Cronbach α coefficient was 0.87 for the questionnaire and 0.84 to 0.86 for its separate items. The repeatability of the questionnaire was good to very good (Cohen κ, 0.76–0.85; P <0.01). The Spearman coefficient for the sum of scores of test–retest responses was 0.95 (P <0.01). The Bland–Altman analysis revealed very good test–retest and interrater reliability, with the mean difference between test I and test II results of –0.556 (95% CI, –0.345 to 0.767). CONCLUSIONS The Polish version of the CAT questionnaire is a reproducible and reliable instrument for evaluation of patients with COPD and should be recommended for use in clinical practice

Melatonin as a Potential Adjuvant Treatment for COVID-19 beyond Sleep Disorders

Melatonin is registered to treat circadian rhythm sleep–wake disorders and insomnia in patients aged 55 years and over. The essential role of the circadian sleep rhythm in the deterioration of sleep quality during COVID-19 confinement and the lack of an adverse effect of melatonin on respiratory drive indicate that melatonin has the potential to be a recommended treatment for sleep disturbances related to COVID-19. This review article describes the effects of melatonin additional to its sleep-related effects, which make this drug an attractive therapeutic option for treating patients with COVID-19. The preclinical data suggest that melatonin may inhibit COVID-19 progression. It may lower the risk of the entrance of the SARS-CoV-2 virus into cells, reduce uncontrolled hyper-inflammation and the activation of immune cells, limit the damage of tissues and multiorgan failure due to the action of free radicals, and reduce ventilator-induced lung injury and the risk of disability resulting from fibrotic changes within the lungs. Melatonin may also increase the efficacy of COVID-19 vaccination. The high safety profile of melatonin and its potential anti-SARS-CoV-2 effects make this molecule a preferable drug for treating sleep disturbances in COVID-19 patients. However, randomized clinical trials are needed to verify the clinical usefulness of melatonin in the treatment of COVID-19

Stanowisko Polskiego Towarzystwa Chorób Płuc i Polskiego Towarzystwa Alergologicznego dotyczące leczenia powikłań płucnych u chorych po przebytym zakażeniu SARS-CoV-2

Celem opracowania jest dostarczenie lekarzom przejmującym opiekę nad chorymi po przebytym zapaleniu płuc COVID-19 wskazówek, dotyczących właściwej diagnostyki i leczenia powikłań płucnych powstałych w następstwie zespołu ciężkiej ostrej niewydolności oddychania po zakażeniu koronawirusem 2 (SARS-CoV-2). Eksperci przedstawiają 32 zalecenia dotyczące leczenia powikłań płucnych (w tym antybiotykoterapii, terapii glikokortykosteroidami, profilaktyki i leczenia przeciwzakrzepowego), rehabilitacji oddechowej, procedur przeszczepienia płuca oraz monitorowania chorych podczas opieki ambulatoryjnej. W pracy omówiono również sposoby postępowania u osób ze współistniejącymi chorobami układu oddechowego (astmą, przewlekłą obturacyjną chorobą płuc, rakiem płuca, chorobami śródmiąższowymi płuc), z uwzględnieniem terapii stosowanych w przebiegu tych chorób — leczenia glikokortykosteroidami i lekami antyfibrotycznymi. Przedstawione wytyczne uwzględniają najnowsze doniesienia i mają na celu zapewnienie optymalnych standardów opieki nad chorymi z powikłaniami płucnymi w następstwie COVID-19

Therapeutic decisions in a cohort of patients with idiopathic pulmonary fibrosis : a multicenter, prospective survey from Poland

BACKGROUND: Pirfenidone and nintedanib are considered as the standard of care in idiopathic pulmonary fibrosis (IPF), but there is no consensus as to which of these two agents should be regarded as first-line treatment. OBJECTIVE: To provide real-world data on therapeutic decisions of pulmonary specialists, particularly the choice of the antifibrotic drug in patients with IPF. METHODS: This was a multicenter, prospective survey collecting clinical data of patients with IPF considered as candidates for antifibrotic treatment between September 2019 and December 2020. Clinical characteristics and information on the therapeutic approach were retrieved. Statistical evaluation included multiple logistic regression analysis with stepwise model selection. RESULTS: Data on 188 patients [74.5% male, median age 73 (interquartile range, 68–78) years] considered for antifibrotic therapy were collected. Treatment was initiated in 138 patients, while 50 patients did not receive an antifibrotic, mainly due to the lack of consent for treatment and IPF severity. Seventy-two patients received pirfenidone and 66 received nintedanib. Dosing protocol (p < 0.01) and patient preference (p = 0.049) were more frequently associated with the choice of nintedanib, while comorbidity profile (p = 0.0003) and concomitant medication use (p = 0.03) were more frequently associated with the choice of pirfenidone. Age (p = 0.002), lung transfer factor for carbon monoxide (TL(CO)) (p = 0.001), and gastrointestinal bleeding (p = 0.03) were significantly associated with the qualification for the antifibrotic treatment. CONCLUSION: This real-world prospective study showed that dose protocol and patient preference were more frequently associated with the choice of nintedanib, while the comorbidity profile and concomitant medication use were more frequently associated with the choice of pirfenidone. Age, TL(CO), and history of gastrointestinal bleeding were significant factors influencing the decision to initiate antifibrotic therapy