Indices of airway resistance and reactance from impulse oscillometry correlate with aerosol particle emission in different age groups.

Airborne transmission of pathogens plays a major role in the spread of infectious diseases. Aerosol particle production from the lung is thought to occur in the peripheral airways. In the present study we investigated eighty lung-healthy subjects of two age groups (20-39, 60-76 years) at rest and during exercise whether lung function parameters indicative of peripheral airway function were correlated with individual differences in aerosol particle emission. Lung function comprised spirometry and impulse oscillometry during quiet breathing and an expiratory vital capacity manoeuvre, using resistance (R5) and reactance at 5 Hz (X5) as indicators potentially related to peripheral airway function. The association between emission at different ventilation rates relative to maximum ventilation and lung function was assessed by regression analysis. In multiple regression analyses including age group, only vital capacity manoeuvre R5 at 15% to 50% of end-expiratory vital capacity as well as quiet breathing X5 were independently linked to particle emission at 20% to 50% of maximum ventilation, in addition to age group. The fact that age as predictive factor was still significant, although to a lower degree, points towards further effects of age, potentially involving surface properties not accounted for by impulse oscillometry parameters.

Enhanced particle separation through ultrasonically-induced microbubble streaming for automated size-selective particle depletion.

In this study, we present an automated method for achieving Size-Selective Particle Depletion in microchannels. This technique is notable for its label-free, sheath-free, and cost-effective attributes. It combines continuous Poiseuille flow with microbubble streaming to enable the manipulation of particles in an automatic or semi-automatic manner at periodic intervals. Larger particles are retained in proximity to the microbubble, with the option for subsequent eviction through a designated waste exit or their accumulation within a collection chamber for future analysis or manipulation. Unlike many conventional methods, our approach keeps the target particles in the vortices near the microbubble while the primary fluid flows continuously through the microchannel. Subsequently, these particles are ejected in just a few milliseconds, preserving the primary fluid and significantly reducing fluid wastage. We conducted an analysis covering multiple critical facets of the study. This included a rigorous statistical examination, flow characterization using volumetric micro PTV, high-frequency micro PTV for observing flow field transitions, evaluating the system's particle trapping capabilities across different sizes with a proprietary algorithm, and investigating the z-axis distribution of both incoming and escaped particles using volumetric micro PTV. The invaluable insights gleaned from this data played a pivotal role in refining the system and optimizing its operational parameters to achieve peak efficiency across various conditions, encompassing varying particle sizes, flow rates, and seeding densities.

Lung aerosol particle emission increases with age at rest and during exercise.

Airborne respiratory aerosol particle transmission of pathogens such as severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), influenza, or rhinoviruses plays a major role in the spread of infectious diseases. The infection risk is increased during indoor exercise, as aerosol particle emission can increase by more than 100-fold from rest to maximal exercise. Earlier studies have investigated the effect of factors such as age, sex, and body mass index (BMI), but only at rest and without taking ventilation into account. Here, we report that during both rest and exercise, subjects aged 60 to 76 y emit on average more than twice as many aerosol particles per minute than subjects aged 20 to 39 y. In terms of volume, older subjects emit on average five times as much dry volume (i.e., the residue of dried aerosol particles) than younger subjects. There was no statistically significant effect of sex or BMI within the test group. Together, this suggests that aging of the lung and respiratory tract is associated with an increased generation of aerosol particles irrespective of ventilation. Our findings demonstrate that age and exercise increase aerosol particle emission. In contrast, sex or BMI only have minor effects.

Respiratory aerosol particle emission and simulated infection risk is greater during indoor endurance than resistance exercise.

Pathogens such as severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), influenza, and rhinoviruses are transmitted by airborne aerosol respiratory particles that are exhaled by infectious subjects. We have previously reported that the emission of aerosol particles increases on average 132-fold from rest to maximal endurance exercise. The aims of this study are to first measure aerosol particle emission during an isokinetic resistance exercise at 80% of the maximal voluntary contraction until exhaustion, second to compare aerosol particle emission during a typical spinning class session versus a three-set resistance training session. Finally, we then used this data to calculate the risk of infection during endurance and resistance exercise sessions with different mitigation strategies. During a set of isokinetic resistance exercise, aerosol particle emission increased 10-fold from 5,400 ± 1,200 particles/min at rest to 59,000 ± 69,900 particles/min during a set of resistance exercise. We found that aerosol particle emission per minute is on average 4.9-times lower during a resistance training session than during a spinning class. Using this data, we determined that the simulated infection risk increase during an endurance exercise session was sixfold higher than during a resistance exercise session when assuming one infected participant in the class. Collectively, this data helps to select mitigation measures for indoor resistance and endurance exercise classes at times where the risk of aerosol-transmitted infectious disease with severe outcomes is high.

High prevalence of p16 staining in malignant tumors.

p16 (CDKN2A) is a member of the INK4 class of cell cycle inhibitors, which is often dysregulated in cancer. However, the prevalence of p16 expression in different cancer types is controversial. 15,783 samples from 124 different tumor types and 76 different normal tissue types were analyzed by immunohistochemistry in a tissue microarray format. p16 was detectable in 5,292 (45.0%) of 11,759 interpretable tumors. Except from adenohypophysis in islets of Langerhans, p16 staining was largely absent in normal tissues. In cancer, highest positivity rates were observed in uterine cervix squamous cell carcinomas (94.4%), non-invasive papillary urothelial carcinoma, pTaG2 (100%), Merkel cell carcinoma (97.7%), and small cell carcinomas of various sites of origin (54.5%-100%). All 124 tumor categories showed at least occasional p16 immunostaining. Comparison with clinico-pathological data in 128 vulvar, 149 endometrial, 295 serous ovarian, 396 pancreatic, 1365 colorectal, 284 gastric, and 1245 urinary bladder cancers, 910 breast carcinomas, 620 clear cell renal cell carcinomas, and 414 testicular germ cell tumors revealed only few statistically significant associations. Comparison of human papilloma virus (HPV) status and p16 in 497 squamous cell carcinomas of different organs revealed HPV in 80.4% of p16 positive and in 20.6% of p16 negative cancers (p<0.0001). It is concluded, that a positive and especially strong p16 immunostaining is a feature for malignancy which may be diagnostically useful in lipomatous, urothelial and possibly other tumors. The imperfect association between p16 immunostaining and HPV infection with high variability between different sites of origin challenges the use of p16 immunohistochemistry as a surrogate for HPV positivity, except in tumors of cervix uteri and the penis.

Aerosol particle emission increases exponentially above moderate exercise intensity resulting in superemission during maximal exercise.

Many airborne pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are transmitted indoors via aerosol particles. During exercise, pulmonary ventilation can increase over 10-fold, and therefore, exercisers will exhale a greater volume of aerosol-containing air. However, we currently do not know how exercise affects the concentration of aerosol particles in exhaled air and the overall emission of aerosol particles. Consequently, we developed a method to measure in parallel the concentration of aerosol particles in expired air, pulmonary ventilation, and aerosol particle emission at rest and during a graded exercise test to exhaustion. We used this method to test eight women and eight men in a descriptive study. We found that the aerosol particle concentration in expired air increased significantly from 56 ± 53 particles/liter at rest to 633 ± 422 particles/liter at maximal intensity. Aerosol particle emission per subject increased significantly by a factor of 132 from 580 ± 489 particles/min at rest to a super emission of 76,200 ± 48,000 particles/min during maximal exercise. There were no sex differences in aerosol particle emission, but endurance-training subjects emitted significantly more aerosol particles during maximal exercise than untrained subjects. Overall, aerosol particle emission increased moderately up to an exercise intensity of ∼2 W/kg and exponentially thereafter. Together, these data might partly explain superspreader events especially during high-intensity group exercise indoors and suggest that strong infection prevention measures are needed especially during exercise at an intensity that exceeds ∼2 W/kg. Investigations of influencing factors like airway and whole-body hydration status during exercise on aerosol particle generation are needed.

Possible tumour cell reimplantation during curative endoscopic therapy of superficial Barrett's carcinoma.

BACKGROUND AND AIMS: Endoscopic resection has been established as curative therapy for superficial cancer arising from Barrett's oesophagus (BE); recurrences are very rare. Based on a case series with unusual and massive early recurrences, we analyse the issue of tumour cell reimplantation. METHODS: This hypothesis was developed on the basis of two out of seven patients treated by circumferential (n=6) or nearly circumferential (n=1) en bloc and R0 endoscopic resection of T1 neoplastic BE. Subsequently, a prospective histocytological analysis of endoscope channels and accessories was performed in 2 phases (cytohistological analysis; test for cell viability) in 22 different oesophageal carcinoma patients undergoing endoscopy. Finally, cultures from two oesophageal adenocarcinoma cell lines were incubated with different triamcinolone concentrations (0.625-10 mg/mL); cell growth was determined on a Multiwell plate reader. RESULTS: Cancer regrowth in the two suspicious cases (male, 78/71 years) occurred 7 and 1 months, respectively, after curative tumour resection. Subsequent surgery showed advanced tumours (T2) with lymph node metastases; one patient died. On cytohistological examinations of channels and accessories, suspicious/neoplastic cells were found in 4/10 superficial and in all 5 advanced cancers. Further analyses in seven further advanced adenocarcinoma cases showed viable cells in two channel washing specimens. Finally, cell culture experiments demonstrated enhanced tumour cell growth by triamcinolone after 24 hours compared with controls. CONCLUSIONS: Tumour cell reimplanation from contaminated endoscopes and accessories is a possible cause of local recurrence after curative endoscopic therapy for superficial Barrett carcinoma; also, corticosteroid injection could have promoted tumour regrowth in these cases.

Flow profiles near receding three-phase contact lines: influence of surfactants.

The dynamics of wetting and dewetting is largely determined by the velocity field near the contact lines. For water drops it has been observed that adding surfactant decreases the dynamic receding contact angle even at a concentration much lower than the critical micelle concentration (CMC). To better understand why surfactants have such a drastic effect on drop dynamics, we constructed a dedicated setup on an inverted microscope, in which an aqueous drop is held stationary while the transparent substrate is moved horizontally. Using astigmatism particle tracking velocimetry, we track the 3D displacement of the tracer particles in the flow. We study how surfactants alter the flow dynamics near the receding contact line of a moving drop for capillary numbers in the order of 10-6. Even for surfactant concentrations c far below the critical micelle concentration (c ≪ CMC) Marangoni stresses change the flow drastically. We discuss our results first in a 2D model that considers advective and diffusive surfactant transport and deduce estimates of the magnitude and scaling of the Marangoni stress from this. Modeling and experiment agree that a tiny gradient in surface tension of a few µN m-1 is enough to alter the flow profile significantly. The variation of the Marangoni stress with the distance from the contact line suggests that the 2D advection-diffusion model has to be extended to a full 3D model. The effect is ubiquitous, since surfactant is present in many technical and natural dewetting processes either deliberately or as contamination.

Bronchoscopic performance of bronchoalveolar lavage in germany - a call for standardization.

BACKGROUND: Bronchoalveolar lavage (BAL) is a widely used clinical tool in diagnosing interstitial lung diseases. Although there are recommendations and guidelines, the procedure is not completely standardized. Varying approaches likely influence the conclusiveness of BAL data and may be one reason for the divergent judgement of their value between different centers. OBJECTIVES: To evaluate how BAL is performed in Germany using an electronically based survey. METHODS: We conducted a cross-sectional online survey among all members of the German Respiratory Society. RESULTS: 608 members responded to the survey and of these 500 perform lavages. Most bronchoscopists (344/500) do not use a tube and have no anesthesiologist present during the procedure (405/500). Propofol is used by 76.8% and midazolam by 67.9% (n = 405), often in combination. A major difference was noted regarding the total volume of instillation. Many respondents use a predefined fixed amount of instilled volume (202/500), whereas an almost equal number use variable volumes based on the recovery (196/500). The minimum recovery volume predefined by 217/499 ranged from 3-150 ml (median 30 ml; mean 42.2 ± 55.1 ml). Most respondents did not transport their samples in special medium (61.5%) or on ice (72.8%). The average time between recovery and arrival at the lab was 115.6±267.0 min (n = 323). CONCLUSION: This study shows the broad spectrum of variations in the performance of BAL in Germany, which could have a negative effect on the method's clinical value. There is a need for training and standardization of BAL performance.

Fundamental protective mechanisms of face masks against droplet infections.

Many governments have instructed the population to wear simple mouse-and-nose covers or surgical face masks to protect themselves from droplet infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in public. However, the basic protection mechanisms and benefits of these masks remain controversial. Therefore, the aim of this work is to show from a fluid physics point of view under which circumstances these masks can protect against droplet infection. First of all, we show that the masks protect people in the surrounding area quite well, since the flow resistance of the face masks effectively prevents the spread of exhaled air, e.g. when breathing, speaking, singing, coughing and sneezing. Secondly, we provide visual evidence that typical household materials used by the population to make masks do not provide highly efficient protection against respirable particles and droplets with a diameter of 0.3-2 µm as they pass through the materials largely unfiltered. According to our tests, only vacuum cleaner bags with fine dust filters show a comparable or even better filtering effect than commercial particle filtering FFP2/N95/KN95 half masks. Thirdly, we show that even simple mouse-and-nose covers made of good filter material cannot reliably protect against droplet infection in contaminated ambient air, since most of the air flows through gaps at the edge of the masks. Only a close-fitting, particle-filtering respirator offers good self-protection against droplet infection. Nevertheless, wearing simple homemade or surgical face masks in public is highly recommended if no particle filtrating respiratory mask is available. Firstly, because they protect against habitual contact of the face with the hands and thus serve as self-protection against contact infection. Secondly, because the flow resistance of the masks ensures that the air remains close to the head when breathing, speaking, singing, coughing and sneezing, thus protecting other people if they have sufficient distance from each other. However, if the distance rules cannot be observed and the risk of inhalation-based infection becomes high because many people in the vicinity are infectious and the air exchange rate is small, improved filtration efficiency masks are needed, to take full advantage of the three fundamental protective mechanisms these masks provide.

Effects of Vibration Training in Interstitial Lung Diseases: A Randomized Controlled Trial.

BACKGROUND: Numerous studies have reported positive effects of exercise training in patients with interstitial lung disease (ILD) on physical capacity and quality of life. However, evidence is rare on the effects of specific forms of training and further pathophysiological mechanisms in these patients. OBJECTIVES: In this multicenter study we aimed to explore the clinical effects of whole-body vibration training (WBVT) in patients with ILD on various outcome measures, including proinflammatory cytokines and myostatin. METHODS: We randomly assigned 26 patients with different forms of multidisciplinary confirmed fibrotic ILDs either to the WBVT group (n = 11; 55% male, 61 ± 14 years old, forced vital capacity 83.2 ± 29.3% predicted, 6-min walking distance [6MWD] 478 ± 79 m) performing 3 months of a standardized training (3 times per week), or to a control training group (CTG, n = 15; 60% male, 63 ± 9 years old, FVC 74.6 ± 20.5% predicted, 6MWD 455 ± 85 m) performing sham WBV training. Training in the two groups was performed on a GalileoTM vibration plate (6-20 vs. 5 Hz). The functional assessments before and after the intervention period included pulmonary function, 6MWD test, chair rise test, ultrasonographic measurement of quadriceps muscle thickness (cross-sectional area), quality of life questionnaires, and serum samples. RESULTS: We observed a significant increase in 6MWD (∆Training = 30 m [12-67], p = 0.024) and a decrease of myostatin (∆Training = -465 pg/mL [-713 to -166], p = 0.008) in the WBVT group. In contrast, no significant differences were observed in the CTG. CONCLUSIONS: The present study demonstrates that WBVT is able to significantly increase 6MWD and decrease myostatin in patients with fibrotic ILDs. Therefore, WBVT seems to be a beneficial and feasible training modality in ILD patients. Clinical Trial Registry: German Clinical Trials Registry (DRKS00012930).

MMR deficiency in urothelial carcinoma of the bladder presents with temporal and spatial homogeneity throughout the tumor mass.

BACKGROUND: Microsatellite instability (MSI), a hypermutator phenotype described in many cancers, has emerged as a predictive biomarker for immune checkpoint inhibitor therapy. Cancer heterogeneity represents a potential obstacle for the analysis of predicitive biomarkers. MSI has been reported in bladder cancer, but data on the possible extent of intratumoral heterogeneity are lacking. METHODS: To study MSI heterogeneity in bladder cancer, a tissue microarray (TMA) comprising 598 muscle-invasive urothelial carcinomas of the bladder was utilized to screen for MSI by immunhistochemistry with antibodies for MLH1, PMS2, MSH2, and MSH6. RESULTS: In 9 cases suspicious for MSI, MMR status was further evaluated by large section examination and polymerase chain reaction (PCR)-based analysis of microsatellites ("Bethesda panel") resulting in the identification of 5 validated MSI cases from 448 interpretable cancers (prevalence 1.1%). MMR deficiency always involved PMS2 loss, in 3 cases with additional loss or reduction of MLH1 expression. Four cancers were MSI-high and 1 was MSI-low in the PCR analysis. Parallel sequencing revealed an inactivating MLH1 mutation in 1 tumor but no further known pathogenic MMR gene mutations were found. Immunostaining of all available 72 cancer-containing tissue blocks of the 5 confirmed bladder cancer with MSI including prior and subsequent biopsies showed complete homogeneity of the MMR protein defects and the status of the 4 MMR proteins did not markedly change in sequential resections. In all 4 cases with noninvasive precursor lesions, MSI was also detectable. CONCLUSION: These data suggest that MSI occurs early in invasive bladder cancer and immunohistochemical MMR analysis on limited biopsy material is sufficient to estimate MMR status of the entire cancer mass.

Interfacial flows in sessile evaporating droplets of mineral water.

Liquid flow in sessile evaporating droplets of ultrapure water typically results from two main contributions: a capillary flow pushing the liquid toward the contact line from the bulk and a thermal Marangoni flow pulling the drop free surface toward the summit. Current analytical and numerical models are in good qualitative agreement with experimental observations; however, they overestimate the interfacial velocity values by two to three orders of magnitude. This discrepancy is generally ascribed to contamination of the water samples with nonsoluble surfactants; however, an experimental confirmation of this assumption has not yet been provided. In this work, we show that a small "ionic contamination" can cause a significant effect in the flow pattern inside the droplet. To provide the proof, we compare the flow in evaporating droplets of ultrapure water with commercially available bottled water of different mineralization levels. Mineral waters are bottled at natural springs, are microbiologically pure, and contain only traces of minerals (as well as traces of other possible contaminants), and therefore one would expect a slower interfacial flow as the amount of "contaminants" increase. Surprisingly, our results show that the magnitude of the interfacial flow is practically the same for mineral waters with low content of minerals as that of ultrapure water. However, for waters with larger content of minerals, the interfacial flow tends to slow down due to the presence of ionic concentration gradients. Our results show a much more complex scenario than it has been typically suspected and therefore a deeper and more comprehensive analysis of the huge differences between numerical models and experiments is necessary.

Nasal high-flow versus noninvasive ventilation in patients with chronic hypercapnic COPD.

Background: Despite the encouraging results of noninvasive ventilation (NIV) in chronic hypercapnic COPD patients, it is also evident that some patients do not tolerate NIV or do not benefit from it. We conducted a study in which COPD patients with stable, chronic hypercapnia were treated with NIV and nasal high-flow (NHF) to compare effectiveness. Methods: In a multi-centered, randomized, controlled, cross-over design, patients received 6 weeks of NHF ventilation followed by 6 weeks of NIV ventilation or vice-versa (TIBICO) between 2011 and 2016. COPD patients with stable daytime hypercapnia (pCO2≥50 mmHg) were recruited from 13 German centers. The primary endpoint was pCO2 changes from baseline blood gas, lung function, quality of life (QoL), the 6 min walking test, and duration of device use were secondary endpoints. Results: A total of 102 patients (mean±SD) age 65.3±9.3 years, 61% females, body mass index 23.1±4.8 kg/m2, 90% GOLD D, pCO2 56.5±5.4 mmHg were randomized. PCO2 levels decreased by 4.7% (n=94; full analysis set; 95% CI 1.8-7.5, P=0.002) using NHF and 7.1% (95% CI 4.1-10.1, P<0.001) from baseline using NIV (indistinguishable to intention-to-treat analysis). The difference of pCO2 changes between the two devices was -1.4 mmHg (95% CI -3.1-0.4, P=0.12). Both devices had positive impact on blood gases and respiratory scores (St. George's Respiratory Questionnaire, Severe Respiratory Insufficiency Questionnaire). Conclusions: NHF may constitute an alternative to NIV in COPD patients with stable chronic hypercapnia, eg, those not tolerating or rejecting NIV with respect to pCO2 reduction and improvement in QoL.

Spicae aetheroleum in uncomplicated acute bronchitis: a double-blind, randomised clinical trial.

BACKGROUND: The trial aimed to evaluate the efficacy and safety of Spicae aetheroleum (Spicae ae.), a phytomedicine obtained by steam distillation of the flowering tops of Lavandula latifolia, as compared to placebo in adult patients with acute bronchitis. METHODS: Patients with uncomplicated acute bronchitis (bronchitis severity score [BSS] ≥ 5 score points) were randomly assigned to treatment with Spicae ae. or placebo in a double-blind, parallel-group design. No additional treatment was admitted. The primary objective was the mean difference of a defined total BSS of 25% between the Spicae ae. and the placebo group after 7 days of full medication dose. Secondary endpoints included the BSS at day 10, additional signs and symptoms of bronchitis, quality of life (QoL) and safety. RESULTS: The mean decrease in BSS at day 7 and day 10 was significant with 4.79 vs. 3.20 (p < 0.005 for a 25% difference) and 6.47 vs. 4.32 (p < 0.009 for a 25% difference) score points respectively in the Spicae ae. (n = 119) vs. placebo group (n = 110). Accordingly, most additional signs and symptoms of acute bronchitis as well as the patients' QoL improved significantly with Spicae ae. as compared to placebo. In all, 258 patients were eligible for safety analysis. The treatment with Spicae ae. was well tolerated; no serious adverse events occurred. CONCLUSION: The defined objectives both for the primary and secondary endpoints have been met. The results of this study provide evidence that Spicae ae. is well tolerated, effective and superior to placebo in the symptomatic treatment of uncomplicated acute bronchitis in adult patients.

Risk stratification strategy and assessment of disease progression in patients with pulmonary arterial hypertension: Updated Recommendations from the Cologne Consensus Conference 2018.

In the summer of 2016, delegates from the German Respiratory Society, the German Society of Cardiology and the German Society of Pediatric Cardiology met in Cologne, Germany, to define consensus-based practice recommendations for the management of patients with pulmonary arterial hypertension (PAH). These recommendations were built on the 2015 European Pulmonary Hypertension guidelines and included new evidence, where available, and were last updated in the spring of 2018. This article focusses on the proposed risk stratification and assessment of disease progression in patients with pulmonary arterial hypertension (PAH), covering 3 parts: In part 1, methods and markers that are recommended to assess severity and progression of PAH are discussed and commented. These updated comments incorporate most recent data as well as challenges arising from the variability of phenotypes of PAH patients with increasing cardiopulmonary comorbidities. In part 2, the proposed ESC/ERS risk stratification strategy is discussed, together with a review of the recent validation studies from different European registries. Finally, in part 3, the working group of the Cologne Consensus Conference provides recommendations on how risk assessment may be implemented in routine clinical practice and may serve clinical decision making.

Targeted therapy of pulmonary arterial hypertension: Updated recommendations from the Cologne Consensus Conference 2018.

In the summer of 2016, delegates from the German Respiratory Society, the German Society of Cardiology and the German Society of Pediatric Cardiology met in Cologne, Germany, to define consensus-based practice recommendations for the management of patients with pulmonary arterial hypertension (PAH). These recommendations were built on the 2015 European Pulmonary Hypertension guidelines and included new evidence, where available. The treatment algorithm for PAH was modified based on the observation that there are now many patients diagnosed with IPAH who are at an advanced age and have significant cardiopulmonary comorbidities. For patients newly diagnosed with classic forms of PAH, i.e. younger patients without significant cardiopulmonary comorbidities, the consensus-based recommendation was to use initial combination therapy as the standard approach. The use of monotherapies was no longer considered appropriate in such patients. The choice of treatment strategies should be based on the risk assessment as proposed in the European guidelines. In patients presenting with a low or intermediate risk, oral combination therapy with endothelin receptor antagonists and phosphodiesterase-5 inhibitors or soluble guanylate cyclase stimulators, respectively, should be used. In high-risk patients, triple combination therapy including a subcutaneous or intravenous prostacyclin analogue should be considered. For patients who suffer from PAH and significant cardiopulmonary comorbidities, initial monotherapy is recommended and the use of combination therapies should be considered on an individual basis. The latter recommendations are based on the scarcity of evidence supporting the use of combination therapy and the higher risk of drug-related adverse events in such patients.

Phenotypes of COPD in an Austrian population : National data from the POPE study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) represents a major global health problem; however, there are no data regarding clinical phenotypes of these patients in Austria. METHODS: This was an analysis from the Austrian cohort of the cross-sectional Phenotypes of COPD in Central and Eastern Europe (POPE) study, which was offered to patients with stable COPD in a real-life setting. Patients were recruited at 5 different outpatient facilities in 3 different provinces in Austria. All consecutive patients aged ≥40 years with a diagnosis of COPD confirmed by a post-bronchodilator forced expired volume in 1 s/forced vital capacity (FEV1/FVC) ratio <0.7 during a stable state (≥4 weeks without exacerbation or worsening of any relevant comorbidities) were considered eligible. The primary aim of this study was to assess the prevalence of phenotypes according to predefined criteria. Secondary aims included analyses of differences in patient characteristics, symptom load, comorbidities, and pharmacological treatment. RESULTS: Among 283 patients fulfilling the inclusion criteria, 49.5% were considered non-exacerbators, 21.6% were classified as exacerbators with chronic bronchitis, 21.2% exacerbators without chronic bronchitis, and 7.8% were patients with an asthma-COPD overlap. Exacerbators had significantly higher prevalence of symptoms, lower lung function and exercise capacity, and a higher prevalence of comorbidities, such as heart failure and depression, compared with the other patient phenotypes. A large majority of patients with stable COPD in this cohort received inhaled triple therapy, irrespective of exacerbation history. CONCLUSIONS: There were significant differences in COPD outcome measures between predefined phenotypes of COPD in this study. The majority of patients with stable COPD in this Austrian population were not treated according to current COPD guidelines. While non-exacerbators appear to have been overtreated, patients with an asthma-COPD overlap appear to have been undertreated.

Clogging in constricted suspension flows.

The flow of a charged-stabilized suspension through a single constricted channel is studied experimentally by tracking the particles individually. Surprisingly, the behavior is found to be qualitatively similar to that of inertial dry granular systems: For small values of the neck-to-particle size ratio (D/d<3), clogs form randomly as arches of the particle span the constriction. The statistics of the clogging events are Poissonian as reported for granular systems and agree for moderate particle volume fraction (ϕ≈20%) with a simple stochastic model for the number of particles at the neck. For larger neck sizes (D/d>3), even at the largest ϕ(≈60%) achievable in the experiments, an uninterrupted particle flow is observed, which resembles that of an hourglass. This particularly small value of D/d(≃3) at the transition to a practically uninterrupted flow is attributed to the low effective friction between the particles, achieved by the particle's functionalization and lubrication.