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Glottic web is an abnormal soft tissue adhesion between the vocal cords which occurs due to failure of recanalisation. Congenital glottic webs comprises 5% of laryngeal anomalies. Cohen classified glottic webs into four types based on percentage of airway obliteration. Patients with severe glottic web—grade III and grade IV present with respiratory distress, stridor, phonatory difficulties or recurrent respiratory infections warranting urgent intervention. We are presenting our experience in managing two such patients with severe congenital glottic web. Diagnosis was confirmed by fibreoptic laryngoscopy under monitored anaesthetic care. Combined endoscopic excision of web with laryngofissure approach for keel stenting. In both our patients, we have used a silicone based keel for laryngeal stenting to provide strength and prevent re-webbing. During follow-up, both patients were found to have adequate phonation and normal airway thus demonstrating this method as safe option for adequate phonatory and airway outcomes.

Background: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0–4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2–6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation: In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates. Funding: European Society of Intensive Care Medicine, European Respiratory Society.

The prone position is extensively used to improve oxygenation in patients with severe acute respiratory distress syndrome caused by SARS-CoV-2 pneumonia. Occasionally, these patients exhibit cardiac and respiratory functions so severely compromised they cannot tolerate lying in the supine position, not even for the time required to insert a central venous catheter. The authors describe three cases of successful ultrasound-guided internal jugular vein cannulation in prone position. The alternative approach here described enables greater safety and well-being for the patient, reduces the number of episodes of decompensation, and risk of tracheal extubation and loss of in-situ vascular lines.

Chronic diffuse lung diseases involve a spectrum of nonneoplastic inflammatory conditions that affect the lung parenchyma. This chapter reviews the spectrum of disease including idiopathic interstitial pneumonias, pulmonary manifestations of systemic collagen vascular disease, diffuse eosinophilc lung disease, drug-associated lung disease, diffuse granulomatous lung disease, and a variety of miscellaneous diseases that defy classification. Individual entities are reviewed, followed by a section highlighting a practical approach to the four most common patterns of injury encountered in practice.

Most patients with cystic fibrosis (CF) develop multisystemic clinical manifestations, the minority having mild or atypical symptoms. We describe an adolescent with chronic cough and purulent rhinorrhoea since the first year of life, with diagnoses of asthma, allergic rhinitis and chronic rhinosinusitis. Under therapy with long-acting bronchodilators, antihistamines, inhaled corticosteroids, antileukotrienes and several courses of empirical oral antibiotic therapy, there was no clinical improvement. There was no reference to gastrointestinal symptoms. Due to clinical worsening, extended investigations were initiated, which revealed Pseudomonas aeruginosa in sputum culture, sweat test with a positive result and heterozygosity for F508del and R334W mutations in genetic study which allowed to confirm the diagnosis of CF. In this case, heterozygosity with a class IV mutation can explain the atypical clinical presentation. It is very important to consider this diagnosis when chronic symptoms persist, despite optimised therapy for other respiratory pathologies and in case of isolation of atypical bacterial agents.

Background and Study Aim. In modern sports, the research and study of the functional capabilities of athletes' breathing is relevant. The analysis of individual results made it possible to form an idea about the respiratory functions of athletes. Among elite athletes, parameters of respiratory functions are significantly higher than the norm, so their interpretation relative to the general healthy population is inadequate. The purpose of the study is to determine lung volumes and dynamic parameters of the respiratory act and their difference in height and weight categories, respectively. Material and methods. The study involved 22 elite athletes aged 19-24 took part in the study. Testing of all athletes was carried out during the period of preparation for the competition The following research methods were used: method of anthropometry; method of computer Spirometry (was used to assess the functional state of reserve possibilities of the external breathing of athletes by absolute indicators). The studied material was processed by the methods of mathematical statistics using the "Statistica 6.0" software and MS Excel. Athletes were divided into three groups of height categories: group-A (190 cm and above), group-B (180-189 cm), group-C (170-179 cm) and three weight categories: group-D (90 kg and above), group-E (80-89 kg), group-F (70-79 kg). Results. Studies have shown that the absolute values of respiratory functions in athletes with significant hight and significant body weight are higher than in athletes with short height and insignificant weight. Real indicators of respiratory functions in most athletes are within the normal range. The highest actual indicators of respiratory functions are observed in the group of athletes with average height and average body weight. Also, in elite athletes with average height and average body weight, individual actual indicators are practically the same. Conclusion. Planning and construction of the training process requires knowledge of absolute and actual indicators of respiratory functions. The conducted research made it possible to establish the level of functional reserves of power and mobilization functions of breathing in elite-level rowers. The results allow effective planning of physical activity during training., Передумови та мета дослідження. У сучасному спорті актуальним є дослідження та вивчення функціональних можливостей дихання спортсменів. Аналіз індивідуальних результатів дав змогу скласти уявлення про дихальні функції спортсменів. Серед висококваліфікованих спортсменів показники респіраторних функцій значно вищі за норму, тому їх інтерпретація відносно загальної здорової популяції є неадекватною. Мета дослідження – визначити легеневі об’єми та динамічні параметри дихального акту та їх різницю у зростовій та ваговій категоріях відповідно.Матеріал і методи. У дослідженні взяли участь 22 елітних спортсмени віком 19-24 роки. Тестування всіх спортсменів проводилося в період підготовки до змагань. Використовувалися такі методи дослідження: метод антропометрії; метод комп’ютерної спірометрії (застосовувався для оцінки функціонального стану резервних можливостей зовнішнього дихання спортсменів за абсолютними показниками). Досліджуваний матеріал оброблено методами математичної статистики з використанням програмного забезпечення «Statistica 6.0» та MS Excel. Спортсмени поділялися на три групи зростових категорій: група-А (190 см і вище), група-Б (180-189 см), група-С (170-179 см) і три вагові категорії: група-D (90 кг і вище), група-Е (80-89 кг), група-F (70-79 кг).Результати. Дослідження показали, що абсолютні значення дихальних функцій у спортсменів зі значним зростом і значною масою тіла вищі, ніж у спортсменів з невисоким зростом і незначною вагою. Реальні показники дихальних функцій у більшості спортсменів знаходяться в межах норми. Найвищі фактичні показники дихальних функцій спостерігаються в групі спортсменів із середнім зростом і середньою масою тіла. Також у спортсменів із середнім зростом і середньою масою тіла індивідуальні фактичні показники практично однакові.Висновок. Планування і побудова тренувального процесу вимагає знання абсолютних і фактичних показників функцій дихання. Проведені дослідження дали змогу встановити рівень функціональних резервів силових та мобілізаційних функцій дихання у веслувальників елітного рівня. Результати дозволяють ефективно планувати фізичне навантаження під час тренування.

Introduction Foreign body accidents (FBAs) are frequent in children and can be severe, being a common cause of morbidity and mortality and a public health problem. As these accidents are multifactorial, their cause can only be determined by analyzing the clinical details and characteristics of the object. Knowing the associated mechanisms and factors is essential to determine a risk profile and have a preventive, therapeutic, and diagnostic purpose. Objective The present study aimed to describe the incidence of FBAs in otorhinolaryngology according to their anatomical location, focusing on the aerodigestive system. Methods This is a retrospective study performed by reviewing the medical records of 668 cases seen in the emergency department of a tertiary pediatric hospital in São Paulo, state of São Paulo, Brazil, between 2014 and 2017. Results Foreign bodies (FBs) were found in the digestive system (238/668), in the nasal cavities (206/668), in the ears (182/668), in the oropharynx (34/668), and in the respiratory system (8/668). A total of 91.77% of the patients were treated in the emergency room. The main age group affected was Conclusion Multidisciplinary teams should be ready in the emergency room to provide adequate care in FBAs. Early diagnosis, FB removal in the emergency room or the surgical center and follow-up are essential. Developing prevention campaigns including a risk profile for certain products and/or materials, helping to ensure safety for consumers, is necessary. For this, a national database with compulsory notification containing relevant information on FBAs in the pediatric population should be created.

Background: Sleep and circadian disruption (SCD) is common and severe in the ICU. On the basis of rigorous evidence in non-ICU populations and emerging evidence in ICU populations, SCD is likely to have a profound negative impact on patient outcomes. Thus, it is urgent that we establish research priorities to advance understanding of ICU SCD. Methods: We convened a multidisciplinary group with relevant expertise to participate in an American Thoracic Society Workshop. Workshop objectives included identifying ICU SCD subtopics of interest, key knowledge gaps, and research priorities. Members attended remote sessions from March to November 2021. Recorded presentations were prepared and viewed by members before Workshop sessions. Workshop discussion focused on key gaps and related research priorities. The priorities listed herein were selected on the basis of rank as established by a series of anonymous surveys. Results: We identified the following research priorities: establish an ICU SCD definition, further develop rigorous and feasible ICU SCD measures, test associations between ICU SCD domains and outcomes, promote the inclusion of mechanistic and patient-centered outcomes within large clinical studies, leverage implementation science strategies to maximize intervention fidelity and sustainability, and collaborate among investigators to harmonize methods and promote multisite investigation. Conclusions: ICU SCD is a complex and compelling potential target for improving ICU outcomes. Given the influence on all other research priorities, further development of rigorous, feasible ICU SCD measurement is a key next step in advancing the field.

BackgroundA collaboration between the University of Michigan (UM) Cystic Fibrosis Center (CFC) and Marmara University (MU) CFC was initiated in MU through conducting Quality Improvement projects (QIP). The global aim was to improve nutritional status of children with CF (cwCF), with a specific aim to increase the mean BMI percentile (BMIp) for cwCF by 10 percentile points in 12 months. MethodsBody mass index (BMI) percentiles of cwCF were categorized as: nutritionally adequate (BMIp >= 50%); at risk (BMIp 25%-49%); urgently at risk (BMIp 10%-25%); critically at risk (BMIp < 10%). Appropriate interventions were made according to BMIp category every three months. Forced expiratory volume in one-second percent predicted (FEV1pp), and health-related quality of life (HRQoL) were evaluated. ResultsOne hundred and eight-two cwCF with a mean age of 9.1 +/- 4.3 years were included in the project. Baseline BMIp increased from 25.6 to 37.2 at the 12th month (p < 0.001). In the critically at-risk group BMIp increased from 3.6 to 20.5 (p < 0.001), in the urgently at risk group from 15.9 to 30.8 (p < 0.001), in the at risk group from 37.0 to 44.2 (p < 0.079) and in the nutritionally adequate group the increase was from 66.8 to 69.5 (p < 0.301). FEV1pp also improved significantly, from 81.3 +/- 20.6 to 85.9 +/- 20.8 (p < 0.001). Physical functioning, eating problems, and respiratory symptoms domains of the HRQoL evaluation improved (p < 0.05). ConclusionThis project has led to significant improvements in BMIp, FEV1pp and HRQoL of cwCF; similar projects could easily be implemented by centers in other developing countries.

Airway remodeling occurs in chronic asthma leading to increased airway smooth muscle (ASM) mass and extracellular matrix (ECM) deposition. Although extensively studied in murine airways, studies report only selected larger airways at one time-point meaning the spatial distribution and resolution of remodeling are poorly understood. Here we use a new method allowing comprehensive assessment of the spatial and temporal changes in ASM, ECM, and epithelium in large numbers of murine airways after allergen challenge. Using image processing to analyze 20–50 airways per mouse from a whole lung section revealed increases in ASM and ECM after allergen challenge were greater in small and large rather than intermediate airways. ASM predominantly accumulated adjacent to the basement membrane, whereas ECM was distributed across the airway wall. Epithelial hyperplasia was most marked in small and intermediate airways. After challenge, ASM changes resolved over 7 days, whereas ECM and epithelial changes persisted. The new method suggests large and small airways remodel differently, and the long-term consequences of airway inflammation may depend more on ECM and epithelial changes than ASM. The improved quantity and quality of unbiased data provided by the method reveals important spatial differences in remodeling and could set new analysis standards for murine asthma models.

In speaking, shouting, and singing, vocal loudness is known to be regulated with lung pressure, but the degree to which vocal fold adduction and airway shape play a role in loudness control is less well known. When loudness is quantified in sones instead of sound pressure level (SPL), the regulatory mechanisms are even less obvious. Here it is shown computationally that loudness is insensitive to changes in SPL produced with variable adduction. A trade-off exists between a reduction in glottal flow amplitude and a flatter spectral slope. When the airway configuration is changed from a uniform tube to a "belt" or "call" shape, loudness can increase with a slight decrease in SPL. When the airway configuration is changed from a uniform tube to an operatic "ring" shape, loudness is increased with only a small increase in SPL.

The management of airway and chest wall tumours is a highly specialized area in thoracic surgery which affects a small number of the wider patient population. Familiarization with thoracic anaesthesia, rigid bronchoscopy, LASER technology, airway stenting not only provides stabilization of the airway and relieves obstruction to breathing but provides lifesaving treatment.

OBJECTIVES: We sought to investigate how race, ethnicity, and socioeconomic status relate to tracheostomy insertion and post-tracheostomy mortality among infants with bronchopulmonary dysplasia. METHODS: The Vizient Clinical Database/Resource Manager was queried to identify infants born ≤32 weeks with bronchopulmonary dysplasia admitted to United States hospitals from January 2012-December 2020. Markers of socioeconomic status were linked to patient records from the Agency for Healthcare Research and Quality’s Social Determinants of Health Database. Regression models were used to assess trends in annual tracheostomy insertion rate and odds of tracheostomy insertion and post-tracheostomy mortality, adjusting for sociodemographic and clinical factors. RESULTS: There were 40,021 ex-premature infants included in the study, 1,614 (4.0%) of whom received a tracheostomy. Tracheostomy insertion increased from 2012-2017 (3.1% to 4.1%), but decreased from 2018-2020 (3.3% to 1.6%). Non-Hispanic Black infants demonstrated a 25% higher odds (aOR 1.25, 1.09-1.43) and Hispanic infants demonstrated a 20% lower odds (aOR 0.80, 0.65-0.96) of tracheostomy insertion compared to non-Hispanic White infants. Patients receiving public insurance had increased odds of tracheostomy insertion (aOR 1.15, 1.03-1.30), but there was no relation between other metrics of socioeconomic status and tracheostomy insertion within our cohort. In-hospital mortality among the tracheostomy-dependent was 14.1% and was not associated with sociodemographic factors. CONCLUSIONS: Disparities in tracheostomy insertion are not accounted for by differences in socioeconomic status or the presence of additional neonatal morbidities. Post-tracheostomy mortality does not demonstrate the same relationships. Further investigation is needed to explore the source and potential mitigators of the identified disparities.

It is evident that sex and gender differences impact pathophysiology, disease burden, and treatment outcomes for a variety of systems and major illnesses including those affecting the unified airway. Important male-female differences in unified airway disease are driven by various intrinsic and extrinsic mechanisms including anatomic, morphometric, hormonal, genetic (and epigenetic), environmental, psycho-social, and comorbidity-related factors. This review highlights current knowledge of how patient sex influences epidemiology, diagnosis, treatment, and outcomes for diseases affecting the unified airway.

Stenting for lower tracheal stenosis is a tricky situation and for the safe conduct of anesthesia, it is imperative to maintain spontaneous respiration. Airway topicalization is routinely recommended for anticipated difficult airway. We report a case of upper airway obstruction following lidocaine nebulization in a patient to be taken for tracheal stenting for lower tracheal stenosis. We would like to highlight that close monitoring of the patient is advisable during airway topicalization to detect any airway obstruction at the earliest and how fiberoptic intubation can play a pivotal role to secure the airway in an emergency scenario.

Eosinophilic gastrointestinal diseases are delayed-type chronic allergic disorders that show gastrointestinal eosinophil dense infiltration, with an exaggerated Th2-type immune reaction considered to be an important mechanism. These diseases can be roughly divided into two types: eosinophilic esophagitis, mainly found in young and middle-aged men, and eosinophilic gastroenteritis, which is found in both genders equally. A diagnosis of eosinophilic esophagitis is suspected when characteristic endoscopic findings, including longitudinal furrows and rings, are noted. However, characteristic endoscopic abnormalities are rarely found in cases with eosinophilic gastroenteritis, so multiple biopsy sampling from the apparently normal gastrointestinal mucosal surface is important for making an accurate diagnosis. The administration of systemic glucocorticoid is the standard treatment for eosinophilic gastroenteritis, while acid inhibitors and topical glucocorticoid swallowing therapy are effective for eosinophilic esophagitis. Anti-cytokine therapies for eosinophilic gastrointestinal diseases are currently under development.

Despite centuries of investigation, questions and controversies remain regarding the fundamental genesis and motor pattern of swallow. Two significant topics include inspiratory muscle activity during swallow (Schluckatmung, i.e., “swallow-breath”) and anatomical boundaries of the swallow pattern generator. We discuss the long history of reports regarding the presence or absence of Schluckatmung and the possible advantages of and neural basis for such activity, leading to current theories and novel experimental directions.

Nicotine from cigarette smoke is a biologically active molecule that has pleiotropic effects in the airway, which could play a role in smoking-induced lung disease. However, whether nicotine and its metabolites reach sustained, physiologically relevant concentrations on airway surfaces of smokers is not well defined. To address these issues, concentrations of nicotine, cotinine, and hydroxycotinine were measured by mass spectrometry (MS) in supernatants of induced sputum obtained from participants in the subpopulations and intermediate outcome measures in COPD study (SPIROMICS), an ongoing observational study that included never smokers, former smokers, and current smokers with and without chronic obstructive pulmonary disease (COPD). A total of 980 sputum supernatants were analyzed from 77 healthy never smokers, 494 former smokers (233 with COPD), and 396 active smokers (151 with COPD). Sputum nicotine, cotinine, and hydroxycotinine concentrations corresponded to self-reported smoking status and were strongly correlated to urine measures. A cutoff of ∼8–10 ng/mL of sputum cotinine distinguished never smokers from active smokers. Accounting for sample dilution during processing, active smokers had airway nicotine concentrations in the 70–850 ng/mL (∼0.5–5 µM) range, and concentrations remained elevated even in current smokers who had not smoked within 24 h. This study demonstrates that airway nicotine and its metabolites are readily measured in sputum supernatants and can serve as biological markers of smoke exposure. In current smokers, nicotine is present at physiologically relevant concentrations for prolonged periods, supporting a contribution to cigarette-induced airway disease.

Hypersensitivity reactions are characterized by inappropriate response of the immune system to an inciting antigen, which results in damage to various body tissues. Respiratory system can be involved as a part of hypersensitivity reaction by a myriad of conditions ranging from infective pathologies like tuberculosis to non-infective processes such as asthma, graft- versus host disease, sarcoidosis and vasculitic disorders. Recognition of specific imaging features in appropriate clinical setting helps in diagnosing these conditions. We present a review of mechanism of different types of hypersensitivity reactions; and imaging features of various such pathological conditions affecting the respiratory system.

Rupture of a racemose hemangioma causing dilatation and tortuosity of the bronchial artery can result in massive bleeding and respiratory failure. Bronchial artery embolization (BAE) can treat this life-threatening condition, as we show in two cases. The first case was of an 89-year-old female complaining of sudden-onset chest and back pain. Bronchial artery angiography demonstrated a racemose hemangioma with a 2 cm aneurysm. The second case was of a 50-year-old male with hemoptysis and dyspnea, eventually requiring intubation. Bronchial arteriography showed a racemose hemangioma and a bronchial artery-pulmonary arterial fistula. BAE was successfully performed in both cases, with no recurrent hemorrhage. Therapeutic interventions in bronchial artery racemose hemangiomas include lobectomy or segmentectomy, bronchial arterial ligation, and BAE. BAE should be considered as first-line therapy for bleeding racemose hemangiomas of the bronchial artery because of its low risk of adverse effects on respiratory status, minimal invasiveness, and faster patient recovery.

Introduction Desmoplastic malignant pleural mesothelioma (DMPM) is a sarcoma type mesothelioma, comprising about 5% of malignant pleural mesotheliomas. Although effusion cytology is commonly used as the primary diagnostic approach for mesothelioma, this may not be useful for DMPM due to its desmoplastic nature and bland cellular atypia. We hereby report a case of DMPM diagnosed through autopsy along with its cytological features that have not been described previously. Case presentation A male in his 60s with a history of occupational asbestos exposure was referred to our hospital with right chest pain. Chest computed tomography scan showed right pleural effusion. Thirteen months later, the patient died of respiratory failure. In autopsy, the scrape-imprint smear and the pleural effusions cytology were performed. The scrape-imprint smear samples exhibited spindle cells with mild nuclear atypia and grooves with fibrous stroma. In the pleural effusion cytology, spindle cells having mild nuclear atypia and grooves with loose epithelial connections were observed. Histological examination of the right pleura showed spindle cells proliferating with dense collagen fibers, as seen in cytological samples, thus rendering the diagnosis of DMPM. Diagnosis was confirmed by fluorescence in situ hybridization. Conclusion Cytological procedures, such as pleural effusion cytology and scrape-imprinting method, may be useful as an ancillary tool in the diagnosis of rare tumors such as DMPM.

Background: Asthma is a chronic inflammatory condition of the airways with a complex pathophysiology. Stratification of asthma subtypes into phenotypes and endotypes should move the field forward, making treatment more effective and personalized. Eosinophils are the key inflammatory cells involved in severe eosinophilic asthma. Given the health threat posed by eosinophilic asthma, there is a need for reliable biomarkers to identify affected patients and treat them properly with novel biologics. microRNAs (miRNAs) are a promising diagnostic tool. Objective: The aim of this study was to identify serum miRNAs that can phenotype asthma patients. Methods: Serum miRNAs of patients with eosinophilic asthma (N=40) and patients with noneosinophilic asthma (N=36) were evaluated using next-generation sequencing, specifically miRNAs-seq, and selected miRNAs were validated using RT-qPCR. Pathway enrichment analysis of deregulated miRNAs was performed. Results: Next-generation sequencing revealed 15 miRNAs that were expressed differentially between eosinophilic and noneosinophilic asthma patients, although no differences were observed in the miRNome between atopic and nonatopic asthma patients. Of the 15 miRNAs expressed differentially between eosinophilic and noneosinophilic asthma patients, hsa-miR-26a-1-3p and hsa-miR-376a-3p were validated by RT-qPCR. Expression levels of these 2 miRNAs were higher in eosinophilic than in noneosinophilic asthma patients. Furthermore, expression values of hsa-miR-26a-1-3p correlated inversely with peripheral blood eosinophil count, and hsa-miR-376a-3p expression values correlated with FeNO values and the number of exacerbations. Additionally, in silico pathway enrichment analysis revealed that these 2 miRNAs regulate signaling pathways associated with the pathogenesis of asthma. Conclusion: hsa-miR-26a-1-3p and hsa-miR-376a-3p could be used to differentiate between eosinophilic and noneosinophilic asthma.

Reuse of coal fly ash (CFA) as construction materials is one of the sustainable methods for mitigating its environmental impacts. However, the potential leaching of heavy metals and the limited effect on mechanical improvement impede the reuse of CFA. The objective of this research was to investigate the effects of environmental impact and mechanical improvement of the microbially induced calcium carbonate (CaCO3) precipitation (MICP) process on the CFA–soil mixture. Two resources of CFA, named CFA1 and CFA2, were used. CFA1 is classified as off-specification fly ash, and CFA2 is classified as class F-type fly ash. Experimental results showed that the unconfined compressive stress (UCS) of MICP-treated soil increased significantly with the addition of CFA. The MICP-treated 3% CFA1–soil mixture obtained the highest UCS of 2200 kPa, which was much higher than that of the MICP-treated soil (798 kPa). The maximum UCS of the MICP-treated 3% CFA2–soil mixture was 1398 kPa. X-ray diffraction analysis indicated that the main mineral crystal pattern present in the MICP-treated samples was calcite. Scanning electron microscopy images revealed that the formed calcium carbonate worked as a bridge to connect soil particles together, attached to the surface of soil or located in the pore side of soil particles. In addition, the batch leaching test indicated that cadmium (Cd), copper (Cu), magnesium (Mg), nickel (Ni) and zinc (Zn) were detected in the MICP-treated soil. With the addition of CFA, there was no metal exceeding the maximum contaminant level from the MICP-treated CFA1–soil mixture.

Complete tracheal obliteration after tracheostomy remains a considerable challenge for otolaryngologists and pulmonologists. Here, we report for the first time a novel method of interventional bronchoscopy to successfully recanalize complete tracheal obliteration. Three patients with suprastomal tracheal obliteration and tracheostomy dependence were referred to our center for further management. Using interventional bronchoscopy, a TBNA needle was retrogradely inserted from the stoma to locate the original passage through the occlusion, and then its stylet was left as a guide wire for the sequential dilations. Once the tracheal lumen was restored, endoprosthesis would be implanted to maintain the airway patency. All cases achieved successful recanalization with effortless breathing after the treatment and restored phonation. Bronchoscopic retrograde recanalization using a TBNA needle is a promising and effective treatment for complete tracheal obliteration.

Background: Aerosol therapy is used to deliver medical therapeutics directly to the airways to treat respiratory illnesses. A potential side-effect of this form of treatment is the release of fugitive aerosols into the environment and the exposure of caregivers, other patients, and bystanders to potential viral infections. The aim of this work was to use both flow visualisation and aerosol particle characterisation techniques to study the dispersion, concentrations and size distributions of fugitive aerosols emitted during aerosol therapy delivered via a standard mouthpiece.Methods: Aerosol therapy was delivered via a nebuliser, aerosol holding chamber and mouthpiece to a spontaneously breathing adult patient model that could mimic the release of patient-derived bioaerosol. A combination of laser and Schlieren imaging were used to non-invasively visualise the release and dispersion of fugitive aerosol particles. Time varying aerosol particle number concentrations and size distributions were measured with optical particle sizers at clinically relevant positions. Results: The addition of a capture filter to the expiratory port of the mouthpiece significantly reduced the release and spread of fugitive aerosols. Capture filters were effective in curtailing the release of fugitive aerosols of respirable size, ≤ 5 µm in diameter (P ≤ 0.05). Conclusions: The findings suggest that, where possible, capture filters should be added to the expiratory ports of all aerosol therapy devices to prevent airborne transmission of respiratory illnesses and create safer conditions for healthcare workers and patients.

Summary Background & aims ESPEN guidelines advocate that energy needs of critically ill patients with COVID 19 should be assessed using indirect calorimetry, if safely available. This study described energy needs of intubated patients with COVID-19 and explores whether neuromuscular blockade administration (NMBAs) is associated with altered energy expenditure. Methods Resting energy expenditure (REE) and respiratory exchange rate (RER) evaluated among critically ill intubated COVID-19 patients until 28th day of intensive care unit stay (ICU–S) by indirect calorimetry. Paralysed patients were defined as those with drug induced paralysis using cicatracurium, for at least 3 days during their ICU-S. Results 34 adult COVID 19 patients (59.8% male, 35.2% obese) requiring mechanical ventilation were assessed prospectively. REE measurements suggest a gradual increase of energy needs post 3rd day of ICU-S in both patients without obesity (non ob) ((from 17.8 kcal/kgr up to 29.3 kcal/kgr actual body weight (AcBW) during 28th day of ICU-S, p = 0.011)) and patients with obesity (ob) ((from 18.1 kcal/kgr up to 30.1 kcal/kgr adjusted body weight (AjBW) during 28th day of ICU-S, p = 0.021)). NMBAs use was accompanied by a significant drop in REE, especially during first 7 days of hospitalization, both in non ob (22.9 vs 17.9 kcal/kgr AcBW, p = 0.014) and ob patients (22.5 vs 19.5 kcal/kgr ABW, p = 0.027). Conclusion We identified the energy needs of COVID-19 intubated patients and highlighted a significant increase beyond the 1st week in the ICU. Administration of NMBAs should be considered, as it may impact resting energy expenditure.

The objective was to compare clinical protection [evaluated through health scoring, endoscopy score of the upper respiratory tract (URT-ES), leukocyte count, viremia, and virus shedding in nasal secretions] following Bovine viral diarrhea virus 2 (BVDV2) and Bovine herpes virus 1 (BHV1) challenge among calves submitted to modified-live virus (MLV) booster vaccination (either intranasal or subcutaneous) concurrent with injectable trace minerals (ITM) or saline. Forty-eight dairy calves received an MLV intranasal (IN) vaccine containing BHV1, BRSV, and BPI

Background Interstitial lung disease (ILD) is associated with substantial morbidity and mortality, which is one of the key systematic manifestations of connective tissue disease (CTD). Tripterygium wilfordii, known as Leigongteng in Chinese, has been applied to treat connective tissue disease-related interstitial lung disease (CTD-ILD) for many years. Triptolide is a key effective component from Tripterygium wilfordii. But the molecular mechanism of Triptolide for treating CTD-ILD is not yet clear. Methods Gaining insight into the molecular mechanism of Triptolide intervention CTD-ILD, we used the method of network pharmacology. And then we conducted drug-target networks to analyse the potential protein targets between Triptolide and CTD-ILD. Finally, AutoDock Vina was selected for molecular docking. Results By analysing the interaction genes between Triptolide and CTD-ILD, 242 genes were obtained. The top 10 targets of the highest enrichment scores were STAT3, AKT1, MAPK1, IL6, TP53, MAPK3, RELA, TNF, JUN, JAK2. GO and KEGG enrichment analysis exhibited that multiple signalling pathways were involved. PI3K-Akt, multiple virus infections, cancer signalling, chemokine, and apoptosis signalling pathway are the main pathways for Triptolide intervention CTD-ILD. And it is related to various biological processes such as inflammation, infection, cell apoptosis, and cancer. Molecular docking shows Triptolide can bind with its target protein in a good bond by intermolecular force. Conclusions This study preliminarily reveals the internal molecular mechanism of Triptolide interfere with CTD-ILD through multiple targets, multiple access, validated through molecular docking.KEY MESSAGES Triptolide intervention CTD-ILD, which are related to various biological processes such as inflammation, infection, cell apoptosis, and cancer. PI3K-Akt, multiple virus infections, and apoptosis signalling pathway are the main pathways for Triptolide intervention CTD-ILD. Triptolide can bind with related target protein in a good bond by Intermolecular force, exhibiting a good docking activity.

Abstract: The human has two lungs responsible for respiration and drug metabolism. Severe lung infection caused by bacteria, mycobacteria, viruses, fungi, and parasites may lead to lungs injury. Smoking and tobacco consumption may also produce lungs injury. Inflammatory and pain mediators are secreted by alveolar macrophages. The inflammatory mediators, such as cytokines, interleukin (IL)-1, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α, neutrophils, and fibroblasts are accumulated in the alveoli sac, which becomes infected. It may lead to hypoxia followed by severe pulmonary congestion and the death of the patient. There is an urgent need for the treatment of artificial respiration and ventilation. However, the situation may be the worst for patients suffering from lung cancer, pulmonary tuberculosis, and acute pneumonia caused by acute respiratory distress syndrome (ARDS). Re-urgency has been happening in the case of coronavirus disease of 2019 (COVID-19) patients. Therefore, it is needed to protect the lungs with the intake of natural phytomedicines. In the present review, several selected phyto components having the potential role in lung injury therapy have been discussed. Regular intake of natural vegetables and fruits bearing these constituents may save the lungs even in the dangerous attack of SARS-CoV-2 in lung cancer, pulmonary TB, and pneumatic patients.

Summary Background & aims Sarcopenia, a loss of muscle mass, quality and function, which is particularly evident in respiratory muscles, has been associated with many clinical adverse outcomes. In this study, we aimed at evaluating the role of reduced muscle mass and quality in predicting ventilation weaning, complications, length of intensive care unit (ICU) and of hospital stay and mortality in patients admitted to ICU for SARS-CoV-2-related pneumonia. Methods This was an observational study based on a review of medical records of all adult patients admitted to the ICU of a tertiary hospital in Milan and intubated for SARS-CoV-2-related pneumonia during the first wave of the COVID-19 pandemic. Muscle mass and quality measurement were retrieved from routine thoracic CT scans, when sections passing through the first, second or third lumbar vertebra were available. Results A total of 81 patients were enrolled. Muscle mass was associated with successful extubation (OR 1.02, 95% C.I. 1.00–1.03, p = 0.017), shorter ICU stay (OR 0.97, 95% C.I. 0.95–0.99, p = 0.03) and decreased hospital mortality (HR 0.98, 95% C.I. 0.96–0.99, p = 0.02). Muscle density was associated with successful extubation (OR 1.07, 95% C.I. 1.01–1.14; p = 0.02) and had an inverse association with the number of complications in ICU (Β −0.07, 95% C.I. −0.13 - −0.002, p = 0.03), length of hospitalization (Β −1.36, 95% C.I. −2.21 - −0.51, p = 0.002) and in-hospital mortality (HR 0.88, 95% C.I. 0.78–0.99, p = 0.046). Conclusions Leveraging routine CT imaging to measure muscle mass and quality might constitute a simple, inexpensive and powerful tool to predict survival and disease course in patients with COVID-19. Preserving muscle mass during hospitalisation might have an adjuvant role in facilitating remission from COVID-19.

Effective treatment of pneumonia requires timely administration of appropriate antimicrobials but standard diagnostic tests take around 48 h to generate results. Highly accurate, rapid molecular tests have been developed for identifying organisms in lower respiratory tract samples, however their impact on antibiotic use is unknown. The aim of this study was to assess the impact of syndromic molecular point-of-care testing compared to conventional diagnostic testing, on antibiotic use.In this pragmatic, randomised controlled trial, we enrolled critically ill adults with pneumonia. Patients were assigned (1:1) to molecular testing of samples at the point-of-care or routine clinical care. The primary outcome was the proportion of patients who received results-directed antimicrobial therapy.200 patients were randomly assigned to point-of-care testing (n = 100) or the control group (n = 100). 85 patients had community acquired pneumonia (42 in the mPOCT group and 43 in the control group), 69 hospital acquired pneumonia (30 in mPOCT and 39 in control) and 46 ventilator associated pneumonia (28 in mPOCT and 18 in control). The median [IQR] time to results was 1.7 [1.6-1.9] hours for point-of-care testing and 66.7 [56.7-88.5] hours for standard diagnostics (difference of -65.0 h, 95%CI -68.0 to -62.0; p 0.0001). 71 (71%) patients in the point-of-care testing arm had pathogens detected compared to 51 (51%) in the control arm (difference of 20%, 95%CI 7 to 33; p = 0.004). 80 (80%) of patients in the point-of-care group received results-directed therapy, compared with 29 (29%) of 99 in the control group (difference of 51%, 95%CI 39-63; p 0.0001). Time to results-directed therapy was 2.3 [1.8-7.2] hours in the mPOCT group and 46.1 [23.0-51.5] hours in the control group (difference of -43.8 h, 95% CI -48.9 to -38.6; p 0.0001). 42 (42%) patients in mPOCT group had antibiotics de-escalated compared with 8 (8%) of 98 in the control group (difference of 34%, 95%CI 23-45; p 0.0001). Time to de-escalation was 4.8 [2.4-13.0] hours in the mPOCT group compared with 46.5 [26.3-48.6] hours in the control group (difference of -41.4 h, 95%CI -53 to -29.7; p 0.0001). There was no major difference in antibiotic duration or in clinical or safety outcomes between the two groups.Use of molecular point-of-care testing in patients with pneumonia returned results more rapidly and identified more pathogens than conventional testing. This was associated with improvements in appropriate antimicrobial use and appeared safe.

Background Enhanced nonpharmaceutical interventions (NPIs) to prevent the Coronavirus Disease 2019 (COVID-19) have shown various levels of impact on common respiratory pathogens. We aimed to analyze the epidemiological changes seen in certain common respiratory viruses found in Taiwanese children (e.g., influenza virus, enterovirus, parainfluenza virus, adenovirus and respiratory syncytial virus (RSV)) after the implementation of public health measures, as well as interpret the possible meaning of these changes. Methods This retrospective observational study examined the viral isolation from children younger than 18 years at a medical center in central Taiwan during the period January 2015 – December 2020, a time frame of six years. Viral isolations prior to the COVID-19 pandemic (January 2015 – December 2019), along with those during the post-COVID-19 period (January – December 2020) were analyzed and compared. Results A total of 6,899 throat swab samples were collected during the pre-pandemic period of 2015 to 2019, with 2,681 of them having a positive result (38.86%). There were a total of 713 samples collected in 2020, with 142 of them showing positive results (19.92%). The overall positive rate of viral isolates significantly decreased in 2020 (p < 0.001). Declines in the isolation of the influenza virus, parainfluenza virus, adenovirus and enterovirus were observed. The RSV surprisingly became the leading isolate, with up to 47 (6.59%) instances in 2020, and showing an unusual peak in the winter of 2020. The rise began in September of 2020 and reached its plateau in November of that year. Conclusions Most respiratory viruses decreased under NPIs regarding SARS-CoV-2. However, the RSV outbreak in the winter of 2020 had shown the limitation of current NPIs. Possible explanations have been discussed in details and public preventive measures should be reinforced for RSV, particularly amongst people having young children both at home and in care centers.

Foam diversion acidizing can effectively solve the problem of acid distribution with severe heterogeneity between and within layers. Based on the foam diversion principle, the gas trap theory, and volume conservation principle, the foam slug diversion acidizing model was established and solved considering the change of bottomhole temperature and deviation factor of foam. The simulation results show that the change of temperature has a great influence on the diversion effect at the initial stage of injection, but a small influence at the middle and late stage. The effect of temperature on the highly permeable layer is greater than that of temperature on the low permeability layer. The deviation factor of foam is mainly controlled by temperature at the initial stage, and by pressure at the middle and late stage, and the whole process shows a downward trend, which has little influence on the diversion effect. The quasi-skin factor of gas trap is the most important parameter that influences the effect of foam diversion. The water saturation of the low permeability layer rises faster than that of the high permeability layer, and the effect of diversion is obvious. The research results have a strong guiding significance for foam diversion acidizing.

Aim:This study aims to compare the gating signals of patients with lung cancer recorded during the planning computed tomography scan with the ones recorded during treatment fractions. The results provide insights into how representative the respiratory signals from the planning scan are for radiation dose partitioning.Materials and methods:The amplitude and frequency of the respiratory signals of 29 patients with lung carcinoma were analysed and compared with the amplitude and frequency of those recorded during their planning scans. Moreover, a cross-correlation analysis was performed between the difference between the planning scan and fractions and features from the planning scan.Results:Two patients showed significantly different amplitude and frequency during treatment fractions compared to those from the planning scan. These patients showed low variances in frequency and amplitude during the different fractions. The difference between planning scan and fractions is correlated with the variances within the planning scan.Findings:Respiratory signals can differ between the planning scan and the fractions. In this case, a new planning scan may be beneficial. The respiratory signals from the planning scan may be predictive of whether the planning scan will be representative and usable as a control measure during radiotherapy fractions.

Objective Transglutaminase (TGM)2 and peroxisome proliferator-activated receptor (PPAR)γ are thought to participate in the pathogenesis of nasal polyp formation in cystic fibrosis (CF). We herein investigated expressions of cystic fibrosis transmembrane conductance regulator (CFTR), TGM2, PPARγ and isopeptide bonds, a reaction product of TGM, in non-CF nasal polyps. Methods Nasal polyps and inferior turbinates were collected from chronic rhinosinusitis patients without CF during transnasal endoscopic sinonasal surgery. Expressions of CFTR, TGM2, isopeptide bonds and PPARγ were examined by fluorescence immunohistochemistry and quantitative RT-PCR. Expression of CFTR was also analyzed by Western blot. Results Immunohistochemical fluorescence of the nasal polyp was significantly lower for CFTR and PPARγ, and significantly higher for TGM2 and isopeptide bonds than that of the turbinate mucosa. Lower expression of CFTR in the nasal polyp than in the turbinate mucosa was also observed in Western blot. Expression of PPARG mRNA was significantly lower in the nasal polyp than in the turbinate mucosa, whereas expressions of CFTR mRNA or TGM2 mRNA did not differ between the two tissues. Immunohistochemical fluorescence for CFTR showed significant negative correlation with that for TGM2 and isopeptide bonds, and significant positive correlation with that for PPARγ. The fluorescence for TGM2 was positively correlated with that for isopeptide bonds and negatively correlated with that for PPARγ. The fluorescence for isopeptide bonds tended to be negatively correlated with that for PPARγ. Conclusions These results suggest a possible role of the CFTR-TGM2-PPARγ cascade in the pathogenesis of nasal polyp formation in non-CF patients as in CF patients.

This study aimed to evaluate the performance of a therapeutic vibrating mesh-type nebulizer for the pulmonary delivery of radioaerosols for lung scintigraphy in healthy subjects. Six healthy subjects (mean age of 28.7 ± 6.2 y) inhaled 2 mL of Tc-99m diethylenetriaminepentaacetic acid (DTPA) and normal saline solution (20 mCi) via the therapeutic vibrating mesh nebulizer (DK010, DELBio, Taipei, Taiwan). The nebulizer’s mass median aerodynamic diameter (MMAD) is between 2.3 μm and 5.0 μm (3.47 ± 0.37 μm) and the nebulization rate is greater than 0.2 ml/min. Scintigraphy was performed to count radioaerosols in the regions of interest to determine the total and regional lung deposition and extrathoracic airway deposition of aerosols, penetration of aerosols, and radioactivity count balance. The total lung deposition of aerosols was 21.2 ± 5.2% (% ex-valve dose), 27.4 ± 8.0% (% ex-device dose) and 13.8 ± 4.1% (% initial dose) in nebulizer. The extrathoracic airway deposition was 4.8 ± 1.1%. The radioactivity count balance was 5.4 ± 3.0%. The ratio of outer vs inner lung deposition (O/I ratio, or penetration index) was 1.89 ± 0.55. The delivery efficiency and the penetration of aerosols to the peripheral lung achieved by the DELBio DK010 vibrating mesh-type nebulizer are similar to the commercialized jet-type nebulizers dedicated for radioaerosol lung scintigraphy nebulizer. The therapeutic vibrating mesh-type nebulizer (DELBio DK010) is feasible for radionuclide lung ventilation scintigraphy.

Objectives: Sputum acid-fact bacilli (AFB) and Xpert examinations are the most commonly used methods in early diagnosis for pulmonary tuberculosis. It becomes difficult for the clinician to initiate treatment in patients with negative sputum smear and Xpert examinations at the stage of diagnosis. Waiting for culture results for diagnosis causes delay in treatment and increases the risk of disease transmission. We aimed to investigate the contribution of bronchoscopic lavage (BL) obtained with flexible fiberoptic bronchoscopy (FOB) to the diagnosis of tuberculosis. Methods: The BL results of 36 patients hospitalized in the tuberculosis clinic who were clinically suspected of tuberculosis, but whose sputum AFB and Xpert results were negative, and whose bronchoscopic lavages were taken by FOB, were retrospectively evaluated. Results: BL Xpert examination was the method that made the most contribution to the diagnosis with a rate of 27.7%. BL smear AFB results did not contribute to the diagnosis statistically. Sputum and BL tuberculosis culture results were found to be close to each other. In total, the diagnosis of 50% of the patients was confirmed. Conclusions: Performing Xpert examinations on bronchoscopic materials of patients with negative sputum examinations significantly increase the rate of early diagnosis.

INTRODUCCIÓN: La Ecografía Pulmonar es una técnica accesible, de bajo costo y que ha demostrado su utilidad en la estratificación pronostica en pacientes con COVID-19. Además, según estudios previos, nos puede orientar hacia la potencial etiología, especialmente en situaciones epidémicas como la actual. PACIENTES Y MÉTODOS: Se reclutaron prospectivamente 40 pacientes, 30 con neumonía por SARS-CoV-2 y 10 por neumonía adquirida en la comunidad (NAC). A los pacientes incluidos, se les realizó tanto una radiografía como ecografía de tórax. RESULTADOS: No hubo diferencias en los 2 grupos en cuanto a las características clínicas y analíticas. Los principales hallazgos ecográficos fueron en el grupo de SARS-CoV-2 la presencia de líneas B confluyentes y consolidaciones subpleurales y la hepatinización en el grupo de NAC. El derrame pleural fue más frecuente en el grupo de NAC. En ningún caso la ecografía pulmonar fue normal. El análisis de las curvas ROC mostró un área bajo la curva para la Ecografía Pulmonar del 89,2% (IC 95%: 75,0- 100%, p

To differentiate arytenoid subluxation and vocal fold paralysis by CT cine mode scanning combined with three-dimensional (3D) reconstruction image.Seventy-six patients with suspected vocal fold dyskinesia were collected. All patients were examined being asked to inhale deeply and then make "Yi" sound continuously during CT scanning with cine mode. The optimal maximum opening and minimum closing phases of glottis were selected and 3D reconstruction images were performed. The length of vocal fold, the width of glottis, and the subglottal convergence angle, anteversion angle, elevation angle, valgus angle, and varus angle of cricoarytenoid joints were measured. Vocal fold deformation was divided into three types: type I, type II, and type III. Kappa test was used to compare the consistency between CT diagnosis and clinical diagnosis. Single-factor analysis of variance was used to analyze the statistical differences among arytenoid subluxation, vocal fold paralysis, and normal vocal fold.There was high consistency between CT diagnosis and clinical diagnosis (k = 0.731, P0.05), as well as significant differences in the opening width of glottis between type I and type III, the valgus and varus angles of cricoarytenoid joints between type I and type II or type III, and the subglottal convergence angles among the three types of vocal fold deformation.CT scanning with cine mode combined with 3D reconstruction can display the changes of larynx structures in vocal fold dyskinesia, and can be used for the differential diagnosis of arytenoid cartilage subluxation and vocal fold paralysis.

Background Interstitial lung disease (ILD) patients often develop lung cancer. However, previous studies on the incidences of lung cancer in ILD patients focused on specific aetiologies, such as idiopathic pulmonary fibrosis (IPF). The lung cancer incidences in these patients have not been investigated, and thus, we aimed to evaluate them here. Methods ILD patients at our hospital were retrospectively reviewed. The cumulative incidences of lung cancer in patients with various ILDs were estimated with Kaplan-Meier curves and compared between ILD groups using log-rank tests. The association between several variables at initial diagnosis and lung cancer development was assessed with Cox proportional hazards regression analysis to identify predictors. Results In all, 606 ILD patients, including 161 with IPF, 133 with non-IPF idiopathic interstitial pneumonias, 160 with chronic hypersensitivity pneumonitis, 87 with connective tissue disease-related ILDs, 19 with pulmonary sarcoidosis, and 46 with other ILDs, were included. Twenty-eight patients developed lung cancer. The cumulative incidences of lung cancer at 1, 3, and 5 years were: 1.9, 5.7, and 12.3% with IPF, respectively; 0.8, 0.8, and 4.0% in non-IPF idiopathic interstitial pneumonias; 2.0, 4.6, and 11.0% in chronic hypersensitivity pneumonitis; and 1.1, 1.1, and 2.9% in connective tissue disease-related ILDs. IPF patients had a higher incidence of lung cancer than non-IPF idiopathic interstitial pneumonia patients (p = 0.036). A radiological usual interstitial pneumonia pattern, forced vital capacity value, and pack-years were associated with lung cancer development (hazard ratios 2.959, 1.031, 1.011; 95% confidence intervals 1.257–6.963, 1.006–1.057, 1.002–1.020, p = 0.013, 0.017, 0.020, respectively). Conclusions The lung cancer incidence is higher in IPF patients than in non-IPF idiopathic interstitial pneumonia patients and is equally high in patients with chronic hypersensitivity pneumonitis and IPF.

Mucus hyperconcentration in cystic fibrosis (CF) lung disease is marked by increases in both mucin and DNA concentration. Additionally, it has been shown that half of the mucins present in bronchial alveolar lavage fluid (BALF) from preschool-aged CF patients are present in as non-swellable mucus flakes. This motivates us to examine the utility of mucus flakes, as well as mucin and DNA concentrations in BALF as markers of infection and inflammation in CF airway disease.In this study, we examined the mucin and DNA concentration, as well as mucus flake abundance, composition, and biophysical properties in BALF from three groups; healthy adult controls, and two CF cohorts, one preschool aged and the other school aged. BALFs were characterized via refractometry, PicoGreen, immunofluorescence microscopy, particle tracking microrheology, and fluorescence image tiling.Mucin and DNA BALF concentrations increased progressively from healthy young adult controls to preschool-aged people and school-aged people with CF. Notably, mucin concentrations were increased in bronchoalveolar lavage fluid (BALF) from preschool-aged patients with CF prior to decreased pulmonary function. Infrequent small mucus flakes were identified in normal subjects. A progressive increase in the abundance of mucus flakes in preschool and school-aged CF patients was observed. Compositionally, MUC5B dominated flakes from normal subjects, whereas an increase in MUC5AC was observed in people with CF, reflected in a reduced flaked MUC5B/MUC5AC mucin ratio.These findings suggest mucus composition and flake properties are useful markers of inflammatory and infection-based changes in CF airways.

Background Zinc oxide nanoparticles (ZnO-NPs) are used in various products such as rubber, paint, and cosmetics. Our group reported recently that Nrf2 protein provides protection against ZnO-NPs-induced pulmonary inflammation in male mice. The present study investigated the effect of Nrf2 deletion on the lung inflammatory response in female mice exposed to ZnO-NPs. Methods Twenty-four female Nrf2−/− mice and the same number of female Nrf2+/+ mice were each divided into three equal groups and each exposed to ZnO-NPs at either 0, 10 or 30 µg/mouse by pharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and lungs were collected 14 days later to quantify protein level, number of inflammatory cells, and for scoring inflammation histopathologically. The mRNA levels of Nrf2-depedent antioxidant enzymes and proinflammatory cytokine in lung tissue were measured. Results Exposure to ZnO-NPs increased all types of BALF cells and lung inflammation scores in both of female Nrf2−/− and Nrf2+/+ mice, and Nrf2 deletion enhanced ZnO-NPs-induced increase in the number of eosinophils in BALF. Nrf2 deletion enhanced ZnO-NPs-induced downregulation of GR and upregulation of HO-1 and TNFα. Nrf2 deletion decreased mRNA levels of CAT, GcLc and NQO1 and increased that for GcLm and MT-2. ZnO-NPs dose-dependently increased the level of oxidized glutathione (GSSG), and mRNA levels of proinflammatory cytokines/chemokines; KC, MIP-2, IL-6, IL-1β and MCP-1 only in wild-type mice, and Nrf2 deletion decreased total glutathione levels and upregulated the above proinflammatory cytokines/chemokines regardless of level of exposure to ZnO-NPs. Taken together with our previous results in male mice, our results showed a lower susceptibility of females to lung inflammation, relative to males, irrespective of Nrf2 deletion, and that enhancement of ZnO-NPs-induced upregulation of HO-1 and TNFα and downregulation of GR by deletion of Nrf2 is specific to female mice. Conclusion We conclude that Nrf2 provides protection in female mice against increase in BALF eosinophils, probably through down-regulation of proinflammatory cytokines/chemokines and upregulation of oxidative stress-related genes. The study also suggests lower susceptibility to lung inflammation in female mice relative to their male counterparts and the synergistic effects of sex and exposure to ZnO-NPs on mRNA expression of GR, HO-1 or TNFα.

Solubility between ethanol and diesel impedes the application of ethanol in diesel engines. The objective of the experiment is to compare combustion and emission characteristics of ethanol/diesel fuels using biodiesel, n-pentanol, tetrahydrofuran (THF) as cosolvents respectively on a diesel engine under variable engine loads, exhaust gas recirculation (EGR) rates, and injection timings. The results show: All tested blends increase the indicated thermal efficiency (ITE) except at low load, and THF/ethanol/diesel fuel exhibits a higher ITE. The Coefficient of Variations of Indicated Mean Effective Pressure (COVIMEP) of ethanol/diesel blends is higher than that of diesel at low load. Under EGR conditions, ethanol/diesel blends run at lower COVIMEP, especially for biodiesel/ethanol/diesel fuel. At higher loads, all ethanol/diesel blends can decrease carbon monoxide (CO) emissions, especially for THF/ethanol/diesel fuel. Excessive retard of injection timing will increase CO and total hydrocarbon (THC) emissions of ethanol/diesel fuels. The soot emissions of THF/ethanol/diesel fuel are lower than those of n-pentanol/ethanol/diesel fuel under higher EGR rates. The effect of injection timing on soot emissions becomes more pronounced at slightly higher EGR rates. Compared to diesel, biodiesel/ethanol/diesel fuel increases nitrogen oxide (NOx) emissions, especially at medium-low load, whereas n-pentanol/ethanol/diesel and THF/ethanol/diesel fuels reduce NOxat low and high loads, slightly increase NOxemissions at medium loads. In conclusion, THF may be a more promising ethanol/diesel cosolvent compared with high alcohols and biodiesel in terms of fuel economy and emissions, especially under EGR and heavy load conditions.

The object of the research is the painting, Portrait of a Musician’’. Upon closer examination of the painting, we discovered three details. Two have the shape of trachea and bronchi and the third a larynx. By moving the details through the program Paint X we got an image of the larynx, trachea and bronchi. The larynx is presented by thyroid and cricoid cartilage. The characteristic cartilaginous rings are distinguished on the trachea. The right and left main bronchi are also seen. In our opinion, Leonardo da Vinci reflected the elements of the respiratory system in the, Portrait of a Musician’’, thus emphasizing the fact that the bronchi, trachea and larynx are involved in the production of sound.

Cancer cachexia is defined as a multi-factorial syndrome characterised by an ongoing loss of skeletal muscle mass and progressive functional impairment, estimated to affect 50–80% of patients and responsible for 20% of cancer deaths. Elevations in the morbidity and mortality rates of cachectic cancer patients has been linked to respiratory failure due to atrophy and dysfunction of the ventilatory muscles. Despite this, there is a distinct scarcity of research investigating the structural and functional condition of the respiratory musculature in cancer, with the majority of studies exclusively focussing on limb muscle. Treatment strategies are largely ineffective in mitigating the cachectic state. It is now widely accepted that an efficacious intervention will likely combine elements of pharmacology, nutrition, and exercise. However, of these approaches, exercise has received comparatively little attention. Therefore, it is unlikely to be implemented optimally, whether in isolation or combination. In consideration of these limitations, the current review describes the mechanistic basis of cancer cachexia, and subsequently explores the available respiratory- and exercise-focussed literature within this context. The molecular basis of cachexia is thoroughly reviewed. The pivotal role of inflammatory mediators is described. Unravelling the mechanisms of exercise-induced support of muscle via antioxidant and anti-inflammatory effects in addition to promoting efficient energy metabolism via increased mitochondrial biogenesis, mitochondrial function, and muscle glucose uptake provide avenues for interventional studies. Currently available pre-clinical mouse models including novel transgenic animals provide a platform for the development of multi-modal therapeutic strategies to protect respiratory muscles in people with cancer.

Nicholas B Tiller,1 April Kinninger,2 Asghar Abbasi,1 Richard Casaburi,1 Harry B Rossiter,1 Matthew J Budoff,2 Alessandra Adami3 1Institute of Respiratory Medicine and Exercise Physiology, Division of Respiratory and Critical Care Physiology and Medicine, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA; 2Division of Cardiology, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA; 3Department of Kinesiology, University of Rhode Island, Kingston, RI, USACorrespondence: Harry B Rossiter, Institute of Respiratory Medicine and Exercise Physiology, Division of Respiratory and Critical Care Physiology and Medicine, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, 1124 W. Carson Street, CDCRC Building, Torrance, CA, 90502, USA, Tel +1 310-222-8200, Email hrossiter@lundquist.orgIntroduction: Severe chronic obstructive pulmonary disease (COPD) is partly characterized by diminished skeletal muscle oxidative capacity and concurrent dyslipidemia. It is unknown whether such metabolic derangements increase the risk of cardiovascular disease. This study explored associations among physical activity (PA), muscle oxidative capacity, and coronary artery calcium (CAC) in COPDGene participants.Methods: Data from current and former smokers with COPD (n = 75) and normal spirometry (n = 70) were retrospectively analyzed. Physical activity was measured for seven days using triaxial accelerometry (steps/day and vector magnitude units [VMU]) along with the aggregate of self-reported PA amount and PA difficulty using the PROactive D-PPAC instrument. Muscle oxidative capacity (k) was assessed via near-infrared spectroscopy, and CAC was assessed via chest computerized tomography.Results: Relative to controls, COPD patients exhibited higher CAC (median [IQR], 31 [0– 431] vs 264 [40– 799] HU; p = 0.003), lower k (mean ± SD = 1.66 ± 0.48 vs 1.25 ± 0.37 min− 1; p < 0.001), and lower D-PPAC total score (65.2 ± 9.9 vs 58.8 ± 13.2; p = 0.003). Multivariate analysis—adjusting for age, sex, race, diabetes, disease severity, hyperlipidemia, smoking status, and hypertension—revealed a significant negative association between CAC and D-PPAC total score (β, − 0.05; p = 0.013), driven primarily by D-PPAC difficulty score (β, − 0.03; p = 0.026). A 1 unit increase in D-PPAC total score was associated with a 5% lower CAC (p = 0.013). There was no association between CAC and either k, steps/day, VMU, or D-PPAC amount.Conclusion: Patients with COPD and concomitantly elevated CAC exhibit greater perceptions of difficulty when performing daily activities. This may have implications for exercise adherence and risk of overall physical decline.Keywords: coronary artery calcium, COPD, muscle, oxidative capacity, physical activity, respiratory

A 70-year-old woman who had been taking oral steroids with tapering after an acute exacerbation of idiopathic pulmonary fibrosis (IPF) was diagnosed with stage IIIB squamous cell lung cancer by transbronchial lung biopsy from left hilum 6 months before admission. At the time, she had anorexia due to

A 45-year-old man, with poorly controlled diabetes (HbA1c-10.1), presented with fever and gluteal pain for 3 days. On examination, there was a swelling over left gluteal region with induration and an overlying discharging sinus. Ultrasonography of the swelling showed subcutaneous oedema with

The mucus clearance system is the dominant mechanical host defense system of the human lung. Mucus is cleared from the lung by cilia and airflow, including both two-phase gas-liquid pumping and cough-dependent mechanisms, and mucus transport rates are heavily dependent on mucus concentration. Importantly, mucus transport rates are accurately predicted by the gel-on-brush model of the mucociliary apparatus from the relative osmotic moduli of the mucus and periciliary-glycocalyceal (PCL-G) layers. The fluid available to hydrate mucus is generated by transepithelial fluid transport. Feedback interactions between mucus concentrations and cilia beating, via purinergic signaling, coordinate Na+absorptive vs Cl−secretory rates to maintain mucus hydration in health. In disease, mucus becomes hyperconcentrated (dehydrated). Multiple mechanisms derange the ion transport pathways that normally hydrate mucus in muco-obstructive lung diseases, e.g., cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis (NCFB), and primary ciliary dyskinesia (PCD). A key step in muco-obstructive disease pathogenesis is the osmotic compression of the mucus layer onto the airway surface with the formation of adherent mucus plaques and plugs, particularly in distal airways. Mucus plaques create locally hypoxic conditions and produce airflow obstruction, inflammation, infection, and, ultimately, airway wall damage. Therapies to clear adherent mucus with hydrating and mucolytic agents are rational, and strategies to develop these agents are reviewed.