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Lobar atelectasis may be a complication of pulmonary exacerbations in cystic fibrosis (CF). There are no established guidelines on the management of this condition in patients with CF. Therapeutic bronchoscopy with recombinant human deoxyribonuclease (rhDNase) instillation has been described to be successful in patients not responding to conservative measures. We describe a case of a young man with CF, with previously mild impaired lung function, presenting with cough, desaturation, and worsening dyspnea, persisting for over 6 weeks, despite conservative therapy. Thoracic imaging showed right lower lobe atelectasis, which was successfully treated with bronchoscopy and instillation of rhDNase. Long-term resolution of the atelectasis was confirmed with chest magnetic resonance imaging follow-up.

The aim of the study was to study the polymorphism of HIF-1A (rs11549465) and VEGFA (rs2010963) genes and their association with immunological parameters among the miners with lung dust pathology in the Kemerovo region. Material and methods. 200 Kuzbass miners aged from 39 to 58 years, working in the primary occupations with a high risk of occupational pathology, were examined. All the subjects were divided into two groups: the 1st group included 130 cases with a proven diagnosis of dust lung pathology. The 2nd group was a control one represented by 70 workers in the same sanitary and hygienic conditions but without occupational diseases. Polymorphisms of the HIF-1A (rs11549465) and VEGFА (rs2010963) genes were studied by the method of real-time polymerase chain reaction. Immunological parameters were determined by immunoenzyme (immunoglobulins A, M and G) and immunoturbidimetric (haptoglobin, ceruloplasmin and α-1-antitrypsin) methods. Results. The study of the distribution of heterozygous genotypes 1772C/T HIF-1A and -634G/C VEGFA did not reveal statistically significant differences between the miners with dust lung pathology and healthy individuals in the South of the Kemerovo region. However, the study results showed heterozygous polymorphisms HIF-1A and VEGFA, particularly the level of haptoglobin α-1-antitrypsin, ceruloplasmin, and IgM, to affect the immune status of the miners with dust lung pathology. Conclusion. Heterozygous polymorphisms 1772C/T HIF-1A and -634G/C VEGFA can be used to determine the immune response and predict the development of dust lung pathology in miners, as well as the choice of treatment and preventive measures. Contribution: Zhukova A.G. — the concept and design of the study, writing a text; Kazitskaya A.S. — collection and processing of material, statistical processing, editing; Yadykina T.K. — collection and processing of material; Panev N.I. — editing. All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version. Acknowledgement. The study had no sponsorship. Conflict of interest. The authors declare no conflict of interest. Conclusion of the Biomedical Ethics Committee of the Research Institute for Complex Problems of Hygiene and Occupational Diseases: the study was carried out in accordance with the ethical standard of the Bioethical Committee of the Research Institute for Complex Problems of Hygiene and Occupational Diseases, developed in accordance with the Declaration of Helsinki of the World Association “Ethical principles of scientific research with human participation”, as amended in 2013 . and “Rules of Clinical Practice in the Russian Federation” approved by the Order of the Ministry of Health of the Russian Federation No. 266 of June 19, 2003.

Pulmonary infection due to Mycobacterium abscessus occurs in patients with cystic fibrosis, but rarely in immunocompetent children without underlying lung pathology. Treatment is complicated by frequent resistance to many antibiotics. We present a case report of a 4-month-old female infant with 2 months of cough, difficulty feeding, and failure to thrive, with extensive culture-confirmed M. abscessus pulmonary infection without identified immunodeficiency or underlying lung pathology following multidisciplinary evaluation. We describe our complete evaluation including immunodeficiency evaluation incorporating whole-exome sequencing, describe our antibiotic selection and treatment duration given complicated susceptibility pattern of the M. abscessus isolate, and review literature for nontuberculous mycobacterial pulmonary disease in immunocompetent children. A complete multidisciplinary evaluation for underlying lung disease and primary and acquired immunodeficiency should be undertaken in pediatric patients with M. abscessus pneumonia. Confirming macrolide susceptibility through erm(41) gene evaluation is clinically important for isolates with complicated susceptibility pattern.

Background This research characterized mucociliary clearance (MCC) in young children with cystic fibrosis (CF). Methods Fourteen children (5-7 years old) with CF underwent: two baseline MCC measurements (Visits 1 and 2); one MCC measurement approximately 1 year later (Visit 3); and measurements of lung clearance index (LCI), a measure of ventilation inhomogeneity. Results Median (range) percent MCC through 60 min (MCC60) was similar on Visits 1 and 2 with 11.0 (0.9-33.7) and 12.8 (2.7-26.8), respectively (p = 0.95), and reproducible (Spearman Rho = 0.69; p = 0.007). Mucociliary clearance did not change significantly over 1 year with median percent MCC60 on Visit 3 [12.8 (3.7-17.6)] similar to Visit 2 (p = 0.58). Lower percent MCC60 on Visit 3 was significantly associated with higher LCI scores on Visit 3 (N = 14; Spearman Rho = -0.56; p = 0.04). Conclusions Tests of MCC were reproducible and reliable over a 2-week period and stable over a 1-year period in 5-7-year-old children with CF. Lower MCC values were associated with increased ventilation inhomogeneity. These results suggest that measurements of MCC could be used in short-term clinical trials of interventions designed to modulate MCC and as a new, non-invasive test to evaluate early lung pathology in children with CF. Impact This is the first study to characterize mucociliary clearance (MCC) in children with cystic fibrosis (CF) who were 5-7 years old. Measurements of mucociliary clearance were reproducible and reliable over a 2-week period and stable over a 1-year period. Variability in MCC between children was associated with differences in ventilation homogeneity, such that children with lower MCC values had increased ventilation inhomogeneity. These results suggest that measurements of MCC could be used in short-term clinical trials of interventions designed to modulate MCC and as a new, non-invasive test to evaluate early lung pathology in children with CF.

Corbett et al. use the rhesus macaque model to evaluate the ability of the mRNA-1273 (Moderna) COVID-19 vaccine to protect against challenge with the antibody-evading Beta variant of SARS-CoV-2. Their key finding is that the vaccine prevents severe lung pathology, principally because it is able to induce a strong enough antibody resistance to overcome the variant’s relative resistance.

The problem of fibrosing interstitial lung diseases (ILDs) unites specialists from different areas: pulmonologists, radiologists, therapists, rheumatologists, occupational doctors and others. Actual achievements in studying fibrosing ILDs which are connected with development of immunology and molecular biological methods for the determination of biomarkers, new principles of image-diagnostics of lung pathology, search of new therapeutic “targets”, dictate the necessity of integration of knowledge by specialists from different areas of medicine for improvement pharmacotherapy algorithms. These algorithms directed to decrease fibrosis progression in ILDs, improve quality and increase lifespan of the patients.

The study is based on the study of 30 organ complexes from the human thoracic cavity, distributed into 5 age groups with 10-year interval, 6 observations in each group: 1st age group – 20–30 years, 2nd age group – 31–40 years, 3rd age group – 41–50 years, 4th age group – 51–60 years, 5th age group – 61–70 years. All medications were taken from people without heart and lung pathology at forensic autopsy according to the generally accepted method. Based on the results obtained, topographic features of lymph nodes location around the right main bronchus are given, which is of practical interest.

At the beginning of the first wave of the COVID-19 pandemic, a network of outpatient CT centers (OCTC) for lung pathology diagnostics in patients with suspected viral pneumonia with the round-the-clock operation was formed in Moscow. The introduction of the CT 0-4 scale allowed for effective routing. To prevent the spread of infection among patients and staff, OCTC zoning was introduced, dividing into red, buffer, and green zones. As part of the mobilization of the Radiology Service, the Moscow Reference Center was established, aimed at quality control, remote expert consultations, and organizational and methodological support. Several online courses and training webinars have been developed. Artificial Intelligence services were connected to recognize the signs of COVID-19 and assess the severity. The developed strategy of the Moscow Radiology Service ensured readiness for the high burden on the city health care system and minimized losses among medical personnel. The experts significantly contributed to effective infection control through accessible, timely, and high-quality diagnostics and routing.

Key Clinical Points Evaluation and Management of Severe Covid-19 Patients with severe coronavirus disease 2019 (Covid-19) may become critically ill with acute respiratory distress syndrome that typ...

Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a potentially fatal infectious disease requiring long treatment duration with multiple antibiotics and against which there is no reliable cure. Among the factors that have hampered the development of adequate drug regimens is the lack of an animal model that reproduces the NTM lung pathology required for studying antibiotic penetration and efficacy. Given the documented similarities between tuberculosis and NTM immunopathology in patients, we first determined that the rabbit model of active tuberculosis reproduces key features of human NTM-PD and provides an acceptable surrogate model to study lesion penetration. We focused on clarithromycin, a macrolide and pillar of NTM-PD treatment, and explored the underlying causes of the disconnect between its favorable potency and pharmacokinetics and inconsistent clinical outcome. To quantify pharmacokinetic-pharmacodynamic target attainment at the site of disease, we developed a translational model describing clarithromycin distribution from plasma to lung lesions, including the spatial quantitation of clarithromycin and azithromycin in mycobacterial lesions of two patients on long-term macrolide therapy. Through clinical simulations, we visualized the coverage of clarithromycin in plasma and four disease compartments, revealing heterogeneous bacteriostatic and bactericidal target attainment depending on the compartment and the corresponding potency against nontuberculous mycobacteria in clinically relevant assays. Overall, clarithromycin's favorable tissue penetration and lack of bactericidal activity indicated that its clinical activity is limited by pharmacodynamic, rather than pharmacokinetic, factors. Our results pave the way toward the simulation of lesion pharmacokinetic-pharmacodynamic coverage by multidrug combinations to enable the prioritization of promising regimens for clinical trials.

Sepsis is an inflammatory disease characterized by dysregulation of inflammation. Macrophage-mediated inflammation has been implicated in the pathophysiology of sepsis. Itaconate is a metabolite produced in activated macrophages which has anti-inflammatory activities. In the present study, we investigated the potential effects of a cell-permeable itaconate derivative dimethyl itaconate on inflammation in sepsis. We established a lipopolysaccharide (LPS)-induced septic mouse model and administered dimethyl itaconate to the septic mice. The survival rate, serum level of pro-inflammatory cytokines, and lung pathology were evaluated. We also administered dimethyl itaconate to LPS-treated bone marrow–derived macrophages (BMDMs), and measured the cytokine production and Nrf2 expression. We also evaluated the effects of dimethyl itaconate on Nrf2-deficient mice. Administration of dimethyl itaconate enhanced survival rate, decreased serum level of TNF-α and IL-6, and ameliorated lung injury in septic mice. Dimethyl itaconate also suppressed LPS-induced production of TNF-α, IL-6, and NOS2 in BMDMs. Dimethyl itaconate activated Nrf2 and promoted the expression of Nrf2 and its downstream factor HO-1 and NQO-1. The regulatory activities of dimethyl itaconate on inflammatory cytokine production, mouse survival rate were abolished in septic Nrf2−/− mice. Dimethyl itaconate suppressed the inflammatory responses of macrophages in sepsis.

Inflammatory myofibroblastic tumor is a neoplasia of unknown clinical etiology that clinically and radiologically tends to mimic a malignant neoplasm. The tumor is histologically composed of a mixture of inflammatory cells, myofibroblastic spindle cells and plasma cells. It can occur in any part of the body. Although pulmonary inflammatory myofibroblastic tumor is the most common primary lung mass especially in childhood, this entity is usually not considered in differential diagnosis of lung nodules or masses. In this article, we aimed to disscus the pathology and imaging findings of the pulmonary inflammatory myofibroblastic tumor and increase the familiarity of radiologists and clinicians to this entity.

Acute Respiratory Distress Syndrome (ARDS) is a well-recognized clinical problem first described in the late sixties. However, its relevance seems to have increased since the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) outbreak, as 14% (CI 95% 2% to 59%) of patients admitted to the hospital present with this syndrome. Conceptually, a syndrome is a group of symptoms and signs that correspond to several diseases. Although defining disease is much harder than may appear at first glance, we can view it as the association between a syndrome and a pathology pattern. Diffuse alveolar damage (DAD) is the morphological hallmark of ARDS, although studies performed in autopsies and patients have demonstrated that it is present in only half of ARDS patients. The SARS-CoV-2 outbreak and the high incidence of ARDS associated with this infection have triggered a natural question: is the lung pathology similar in patients with ARDS associated with traditional risk factors than to SARS-CoV-2 infection? This review aims to analyze the lung pathology results of patients infected with the novel SARS Cov-2. As this article targets non-intensive care physicians, we will first describe the main characteristics of the novel SARS-Cov-2 and the ARDS definition, and then the lung pathology results from the UCI in this group of patients.

The objective : basing on published data, to highlight the main issues of preparation of patients with concomitant lung pathology and a high risk of developing postoperative pulmonary complications for planned surgical interventions. Results : changes made to international guidelines over the past 5 years based on evidenc e-b ased studies and met a-a nalyzes have been analyzed. The article presents data on preoperative management of patients with concomitant lung pathologies and a high risk of postoperative pulmonary complications, assessment of the risk of developing these complications based on evaluation of the functional status of patients. It analyzes the contemporary recommendations on the perioperative prevention of pulmonary complications, the use of physical exercises and respiratory gymnastics in the perioperative period in patients with a high risk of postoperative pulmonary complications. It is concluded that the implementation of comprehensive strategy aimed at reducing the risk of pulmonary complications should ensure decrease in their frequency and mortality due to them.

The past 5 years have seen an explosion of interest in the use of artificial intelligence (AI) and machine learning techniques in medicine. This has been driven by the development of deep neural networks (DNNs)—complex networks residing in silico but loosely modelled on the human brain—that can process complex input data such as a chest radiograph image and output a classification such as ‘normal’ or ‘abnormal’. DNNs are ‘trained’ using large banks of images or other input data that have been assigned the correct labels. DNNs have shown the potential to equal or even surpass the accuracy of human experts in pattern recognition tasks such as interpreting medical images or biosignals. Within respiratory medicine, the main applications of AI and machine learning thus far have been the interpretation of thoracic imaging, lung pathology slides and physiological data such as pulmonary function tests. This article surveys progress in this area over the past 5 years, as well as highlighting the current limitations of AI and machine learning and the potential for future developments.

Context.—Transbronchial cryobiopsy is an emerging procedure to obtain lung tissue for diagnosis of interstitial lung disease and has gained popularity because it is less invasive and has a lower rate of complications compared with nonselective surgical lung biopsy.Objective.—To provide an overview of the status of the medical literature regarding transbronchial cryobiopsy.Data Sources.—A literature search was performed using PubMed search engine. The terms “cryobiopsy” or “cryoprobe” and “interstitial lung disease” or “diffuse parenchymal lung disease” or “pulmonary fibrosis” were used, with the search concluding at the end of November 2019.Conclusions.—While the diagnostic yield of transbronchial cryobiopsy is slightly lower than surgical lung biopsy, a growing amount of literature suggests that with a multidisciplinary approach cryobiopsy provides diagnostic and prognostic information approaching that of surgical lung biopsy with lower morbidity and mortality.

E-cigarettes are battery-operated devices that heat a liquid and deliver an aerosolized product to the user. Pulmonary illnesses related to e-cigarette use have been reported, but no large series has been described. In July 2019, the Wisconsin Department of Health Services and the Illinois Department of Public Health received reports of lung injury associated with the use of e-cigarettes (also called vaping) and launched a coordinated public health investigation.We defined case patients as persons who reported use of e-cigarette devices and related products in the 90 days before symptom onset and had pulmonary infiltrates on imaging and whose illnesses were not attributed to other causes. Medical record abstraction and case patient interviews were conducted with the use of standardized tools.There were 98 case patients, 79% of whom were male; the median age of the patients was 21 years. The majority of patients presented with respiratory symptoms (97%), gastrointestinal symptoms (77%), and constitutional symptoms (100%). All case patients had bilateral infiltrates on chest imaging. A total of 95% of the patients were hospitalized, 26% underwent intubation and mechanical ventilation, and two deaths were reported. A total of 89% of the patients reported having used tetrahydrocannabinol products in e-cigarette devices, although a wide variety of products and devices was reported. Syndromic surveillance data from Illinois showed that the mean monthly rate of visits related to severe respiratory illness in June through August of 2019 was twice the rate that was observed in the same months in 2018.Case patients presented with similar clinical characteristics. Although the definitive substance or substances contributing to injury have not been determined, this initial cluster of illnesses represents an emerging clinical syndrome or syndromes. Additional work is needed to characterize the pathophysiology and to identify the definitive causes.

The knowledge on molecular alterations in lung cancer have increased during the last decade considerably. Almost every year new genes were detected being targetable, and drugs have been developed and provided for those patients being diagnosed with such a lung cancer. Therefore, it was necessary to update previous recommendations to facilitate a uniform handling for the diagnosis and molecular tests of lung cancer specimen all over Austria. Originally mutation of the epidermal growth factor receptor (EGFR) was the only actionable molecular alteration, now there are more than 10 driver mutations known, and more are detected, and clinical studies are performed. In addition, the technique to test for these mutations have improved, next generation sequencing has opened the option to test several genes in one test. Immuno-oncology has entered the field, and besides the checkpoint death receptor and ligand molecules PD-1/PD-L1 more molecules have been detected and are also tested in clinical studies. To provide equal opportunities to our patients the tests have to be implemented in all pathological institutes involved in lung cancer management. Because pathologists as part of the tumor board have to explain the diagnosis and the molecular alterations and suggest possible treatment options, the tests should be performed in-house, which will provide the optimal quality control.

T he presented recommendations were developed using own experience of Sechenov University employers (Moscow) and the analysis of international sources related to radiological diagnosis of COVID-19 lung pathology Since the beginning of the pandemic till June 2020, more than 5,000 patients were hospitalized to Sechenov University Clinics and more than 11,000 examinations were performed The recommendations propose patients’ stratification, generalize the radiological patterns of lung changes in COVID-19 patients, provide an extended protocol for describing CT and X-ray data as well as an algorithm for radiological examination in this category of patients П редставленные рекомендации разработаны на основе собственного опыта сотрудников Сеченовского Университета (г Москва) и анализа международных источников, посвященных лучевой диагностике поражений легких при COVID-19 С начала пандемии до июня 2020 года в Клиниках Сеченовского Университета было госпитализировано более 5000 заболевших, которым было выполнено более 11000 исследований В рекомендациях предлагается стратификация пациентов, обобщаются лучевые признаки изменений легких при COVID-19, представляется расширенный протокол описания МСКТ и рентгенографии, а также приводится алгоритм лучевого обследования у данной категории пациентов

Abstract. Anti-inflammatory effect of Curcuma longa ( C. longa) was shown previously. In the present study, the effect of the plant on tracheal responsiveness and lung pathological features in ovalbumin-sensitized rats was evaluated. Six groups of rats including control (C), ovalbumin (OVA)-sensitized (S), S groups treated with C. longa (CL; 0.75, 1.50, and 3.00 mg/ml equal to 150, 300 and 600 mg/kg/day) and dexamethasone (D; 1.25 μg/ml) were studied (n=8 in each group). The extract of C. longa and dexamethasone were administered with daily drinking water of animals during sensitization period (for 21 days). Following the treatment period, tracheal responsiveness to methacholine and ovalbumin and lung pathological features was investigated. Tracheal responsiveness to methacholine and OVA and lung pathological scores were increased in group S compared to controls (p

Background: The smoking of tobacco is one of the most important confounding factors contributing to lung pathology. It is therefore essential to know the degree of prevalence of smoking in the community of former mineworkers of the Transkei, who constitute one of the groups in South Africa most affected by smoking. Objective: Prevalence study of smoking among former mineworkers of Transkei, South Africa Method: This is a record review study from the Benefit Examination Clinic, which was carried out once a week at the chest section of Mthatha Hospital in Transkei. Results: 466 ex-mineworkers were studied for their smoking habits. Non-smokers were lower in number at 97 (21%), the number of ex-smokers was 226 (48%) and smokers numbered 143 (31%). Little more than three-fifth were smokers - 89 (20%) - and ex-smokers - 142 (30%) - who were in their middle age (40-59yrs). Between 1% and 5% were observed to be in the extreme ends of their age groups ( 60). It was observed that among the ex-miners who had worked in the mines for a period of 10 to 19 years, the ex-smokers constituted 26%, the smokers 17% and non-smokers 9%. The ex-smokers, smokers and non-smokers were in a proportion of about 5:3:2. The population of smokers peaked from 15% for those with a mining history of nine or fewer year’s underground to 42% for those who had been mining for 10 to 19 years and fell almost at the same rate from 42% to 22% in the group with 20 or more years of mining. Non-smokers among the sample increased from 5% (nine or fewer years) to 9% in the 10 to 19 years group, and ultimately settled at 7% when they had worked 20 years or more. Conclusion: The prevalence of smoking among ex-mineworkers is high (79%) in the Transkei region of South Africa.

Cigarette smoke, the major risk factor for COPD in developed countries, causes pulmonary inflammation that persists long after smoking cessation, suggesting self-perpetuating adaptive immune responses similar to those that occur in autoimmune diseases. Increases in the number and size of B cell–rich lymphoid follicles (LFs) have been shown in patients in severe stages of COPD (4), and increased B-cell products (autoantibodies) have been observed in the blood and lungs of patients with COPD (5, 6). Oligoclonal rearrangement of the immunoglobulin genes has been observed in B cells isolated from COPD LFs, suggesting that a specific antigenic stimulation drives B-cell proliferation. Consistently, we have shown that in the COPD lung, there is an overexpression of BAFF (B-cell activation factor of the TNF family), which is a key regulator of B-cell homeostasis in several autoimmune diseases (7) and is involved in the growth of LFs in COPD. However, a network analysis of lung transcriptomics showed that a prominent B-cell molecular signature characterized emphysema preferentially but was absent in AD independently of the degree of airflow limitation (8). In the current study, we investigated the correlation between B-cell responses in lung tissue from patients with COPD and healthy smokers, and the extent of emphysema versus airflow limitation.

Bovine respiratory disease (BRD) is the most important and costly health issue of the feedlot industry worldwide. Remote monitoring of reticulorumen temperature has been suggested as a potential tool to improve the diagnostic accuracy of BRD. The present study aimed to evaluate 1) the difference and degree of reticulorumen hyperthermia episodes between healthy and subclinical BRD feedlot steers, and 2) determine the correlation between reticulorumen hyperthermia and lung pathology, performance, and carcass traits. Mixed-breed feedlot steers (n = 148) with a mean arrival weight of 321 ± 3.34 kg were administered a reticulorumen bolus at feedlot entry and monitored for visual and audible signs of BRD until slaughter when lungs were examined and scored for lesions indicative of BRD. Post-slaughter animals with no record of BRD treatment were assigned to one of three case definitions. Healthy steers had no visual or audible signs of BRD (i.e., CIS=1), and total lung consolidation score < 5% or pleurisy score < 3 at slaughter. Subclinical BRD cases had a CIS of 1, and a lung consolidation score ≥ 5% or a pleurisy score of 3 at slaughter. Mild CIS cases had at least one CIS of 2, and a lung consolidation score < 5% and a pleurisy score < 3 at slaughter. Subclinical BRD and mild CIS cases had longer total duration of reticulorumen hyperthermia, more episodes and longer average episode duration above 40.0 °C compared to healthy steers (P < 0.05). A moderate positive correlation was found between lung consolidation and total duration (r = 0.27, P < 0.001), episode duration (r = 0.29, P < 0.001), and number of episodes (r = 0.20, P < 0.05). Pleurisy score was also found to be moderately and positively correlated with total duration (r = 0.23, P < 0.01), episode duration (r = 0.37, P < 0.001), and number of episodes (r = 0.26, P < 0.01). Moderate negative correlations were found between reticulorumen hyperthermia and carcass traits including hot standard carcass weight (HSCW) (−0.22 ≤ r ≤ −0.23, P < 0.05) and P8-fat depth (−0.18 ≤ r ≤ −0.32, P < 0.05). Subclinical BRD reduced carcass weight by 22 kg and average daily gain (ADG) by 0.44 kg/day compared to healthy steers (P < 0.05), but mild CIS cases had no effect on performance (P > 0.05). The reticulorumen bolus technology appears promising for detection of subclinical BRD cases in feedlot cattle as defined by lung pathology at slaughter.

BACKGROUND: The RAM cannula (Neotech, Valencia, CA) has become a commonly used interface for CPAP in neonatal intensive care. Performance characteristics of this interface used with a critical care ventilator are not well described. METHODS: This was a bench study utilizing a lung simulator configured as an actively breathing infant (weights of 800 g, 1.5 kg, and 3 kg) with moderate lung disease and a critical care ventilator in CPAP mode with leak compensation on. Three sizes of the RAM cannulae (preemie, newborn, and infant) were compared to 3 BabyFlow nasal prongs (Dräger Medical, Lübeck, Germany) (medium, large, and extra-large). Fabricated nasal models produced a 70% occlusive fit for the RAM cannula and an occlusive fit with the Dräger prongs. Delivered flow and pressure levels were recorded at 9 CPAP levels between 5 and 20 cm H(2)O. RESULTS: The Dräger prongs produced a mean airway pressure ([Formula: see text]) within 0.20 cm H(2)O (range –0.10 to 0.35) of the set CPAP across all evaluated prong sizes and CPAP levels. In contrast, the RAM cannula produced [Formula: see text] values that averaged 8.5 cm H(2)O (range –15 to –3.5) below the set CPAP levels. The deficit in delivered versus target CPAP level for the RAM cannula increased with greater set CPAP. Set CPAP of 5 cm H(2)O delivered [Formula: see text] values that ranged from 0.6 to 1.5 cm H(2)O (difference of 3.5–4.4 cm H(2)O). Set CPAP of 20 cm H(2)O delivered [Formula: see text] values that ranged from 5.0 to 8.4 cm H(2)O (difference of 11.7–15 cm H(2)O). Inspiratory flow required to achieve set CPAP levels did not differ between interfaces, suggesting high resistance in the RAM cannula device masks the delivered CPAP levels. CONCLUSIONS: Use of the RAM cannula with a 30% leak on a critical care ventilator delivered [Formula: see text] values lower than set CPAP. This may be clinically meaningful and should be considered when choosing a nasal interface.

Inhaled RNA is coming soon for countermeasures against respiratory pathogens, including COVID-19.

INTRODUCTION Hybrid single photon emission computed tomography (SPECT) with CT (SPECT/CT) may improve diagnostic accuracy in suspected acute pulmonary embolism, but further research is needed. We evaluated whether the use of attenuation correction and/or the depiction of lung pathology with hybrid SPECT/CT could significantly reduce potentially false-positive ventilation-perfusion (VQ) SPECT studies or obviate the need for a ventilation study. METHODS Two specialists (S1 and S2) reviewed prospectively acquired VQ SPECT/CT in 165 patients. Studies were reported using standard criteria and compared to VQ SPECT and Q SPECT/CT. RESULTS S1 and S2 recorded positive VQ SPECT in 54 (32.7%) and 42 (25.6%) cases, respectively. Hybrid SPECT/CT showed non-embolic pathology in 41 (S1) and 46 (S2) patients, but compared to VQ SPECT, neither hybrid SPECT/CT nor attenuation correction SPECT/CT had significantly fewer positive studies. Intra-observer agreement with VQ SPECT/CT was almost perfect (k = 0.91 for S1 and k = 0.95 for S2; P

[ABSTRACT] BACKGROUND: Pulmonary alveolar proteinosis is a disease characterized by abnormal accumulation of surfactant in the alveoli. Most cases are autoimmune and are associated with an autoantibody against granulocyte?macrophage colony-stimulating factor (GM-CSF) that prevents clearing of pulmonary surfactant by alveolar macrophages. An open-label, phase 2 study showed some therapeutic efficacy of inhaled recombinant human GM-CSF in patients with severe pulmonary alveolar proteinosis; however, the efficacy in patients with mild-to-moderate disease remains unclear. METHODS: We conducted a double-blind, placebo-controlled trial of daily inhaled recombinant human GM-CSF (sargramostim), at a dose of 125 μg twice daily for 7 days, every other week for 24 weeks, or placebo in 64 patients with autoimmune pulmonary alveolar proteinosis who had a partial pressure of arterial oxygen (Pao2) while breathing ambient air of less than 70 mm Hg (or, Funded by the Japan Agency for Medical Research and Development and the Ministry of Health, Labor, and Welfare of Japan; PAGE ClinicalTrials.gov number, NCT02835742; Japan Medical Association Center for Clinical Trials number, JMA-IIA00205.

Optimal strategies to detect early interstitial lung disease (ILD) are unknown. ILD is frequently subpleural in distribution and affects lung elasticity. Lung ultrasound surface wave elastography (LUSWE) is a noninvasive method of quantifying superficial lung tissue elastic properties. In LUWSE a handheld device applied at the intercostal space vibrates the chest at a set frequency, and the lung surface wave velocity is measured by an ultrasound probe 5 mm away in the same intercostal space. We explored LUWSE's ability to detect ILD and correlated LUSWE velocity with physiological, quantitative, and visual radiologic features of subjects with known ILD and of healthy controls.Seventy-seven subjects with ILD, mostly caused by connective tissue disease, and 19 healthy controls were recruited. LUSWE was performed on all subjects in 3 intercostal lung regions bilaterally. Comparison of LUSWE velocities pulmonary function testing, visual assessment, and quantitative analysis of recent computed tomographic imaging with Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER) software.Sonographic velocities were higher in all lung regions for cases, with the greatest difference in the lateral lower lung. Median velocity in m/s was 5.84 versus 4.11 and 5.96 versus 4.27 (P0.00001) for cases versus controls, left and right lateral lower lung zones, respectively. LUSWE velocity correlated negatively with vital capacity and positively with radiologist and CALIPER-detected interstitial abnormalities.LUSWE is a safe and noninvasive technique that shows high sensitivity to detect ILD and correlated with clinical, physiological, radiologic, and quantitative assessments of ILD. Prospective study in detecting ILD is indicated.

Usual interstitial pneumonia (UIP) pattern is the histologic marker of idiopathic pulmonary fibrosis (IPF), but usefulness of ancillary histologic findings may discriminate idiopathic from secondary UIP.Alternative less invasive procedures may identify UIP pattern preventing conventional surgical lung biopsy, whereas genomic analysis may recognize UIP pattern from otherwise poorly diagnostic samples.High-resolution computed tomography identifies a 'definite' UIP pattern in about half of cases, failing to recognize UIP in the absence of honeycombing or in limited disease. Although radiologic criteria for UIP need redefinition to improve their diagnostic yield, histologic features of UIP did not significantly change from the 1960s but continue to represent a major diagnostic tool, particularly in challenging interstitial lung diseases. A careful recognition of some histologic ancillary findings in UIP (e.g., cellular/follicular bronchiolitis with germinal centers, chronic pleuritis, interstitial granulomas/giant cells, bridging fibrosis) may be helpful in supporting secondary forms (e.g., connective tissue disease, chronic hypersensitivity pneumonia) from IPF. Cryobiopsy and awake-biopsy are promising approaches to obtain representative lung tissue preventing conventional surgical lung biopsy. Genomic techniques have recently demonstrated good-to-high sensitivity and specificity to disclose UIP pattern starting from RNA obtained in transbronchial biopsy, possibly replacing and/or flanking soon traditional histology.

A 52-Year-Old Man with Fever, Cough, and Hypoxemia A 52-year-old man presented to the hospital for evaluation and treatment of hypoxemia. Seven days before presentation, nonproductive cough and a t...

Pleuroparenchymal fibroelastosis (PPFE) is characterized by upper lobe-predominant subpleural fibroelastosis. Despite its characteristic uneven distribution, detailed whole-lung pathological features of PPFE have rarely been studied. We investigated PPFE in the explanted lungs from a 19-year-old male patient with a history of chemotherapy. Grossly, the explanted lungs showed upper lobe-predominant shrinkage with subpleural and central consolidation. Histologically, fibroelastosis was prominent in the perilobular areas and along the bronchovascular bundles. The other areas of the lung showed diffuse, non-specific interstitial pneumonia (NSIP)-like change with a characteristic increase of septal elastic fibers. In the digital image analysis, the ratio of elastic fibers to whole fibrosis (EF score) was lower in the subpleural areas than in the NSIP-like lesions, but the EF scores of the latter showed no significant difference between upper and middle/lower lobes. In the present case, the diffusely distributed elastic fiber-rich NSIP-like change, probably caused by the earlier chemotherapy, may have been conducive to the development of PPFE. This suggests that some unknown vulnerability of the upper lobe may exist, various primary lesions converging to the upper lobe predominance of PPFE.

A Woman with Abdominal Pain and Fever A 38-year-old woman with a history of Crohn’s disease was admitted to the hospital because of abdominal pain and fever. She reported 7 months of progressive sy...

Objective — to analyze medical records, clinical and laboratory research data and autopsies of deceased HIV­infected adults in the hospital, to assess the level of coincidences and discrepancies of clinical and pathologic diagnoses.Materials and methods. A retrospective study of fatal outcomes was conducted at the NIFP NAMS of Ukraine clinic with a verified diagnosis of HIV infection over a 5­year period. In total, 157 people died during this period, 20 of them (12.7 %) had HIV infection. The analysis included a number of clinical and anamnestic data, laboratory parameters presented in the patient’s case histories, as well as the results of macroscopic and microscopic examination at autopsy according to autopsy protocols. Comparison of the final clinical and pathologic diagnoses was made; the main cause of death was established in each case. We took into account the stage of HIV infection at the time of hospitalization of patients, the time of its detection.Results and discussion. Among all the deceased patients with HIV infection, Pneumocystis pneumonia was the most frequent diagnosis — 12 (60.0) % of cases, and it was quite often (10 cases, 83.3 %) combined with other infections — fungal, not identified in vivo (2 cases), cytomegalovirus infection (4 cases), mycobacteriosis (1 case), aspergillosis (2 cases), generalized tuberculosis (1 case). Only in 2 cases without autopsy, pneumocystic pneumonia was diagnosed without indicating other significant lung pathologies. In other cases mycobacterial infection was diagnosed, 5 cases (25.0 %), including verified tuberculosis (2 cases), and two cases — cryptococcal infection, invasive aspergillosis, hepatitis C and fungal infection without laboratory verification of a specific infection. Fatalities with HIV infection occurred at the AIDS stage, with a CD4 cell count below 250/µL. The proportion of discrepancies in the final clinical and pathologic diagnoses was 6 (54.5 %) of 11 cases according to the autopsy results. Moreover, in 5 cases from all 6 discrepancies, this was associated with the development of a fungal/mycobacterial infection. Almost all of the deceased patients had a significant amount of both background diseases and comorbidities, which made their timely intravital diagnostics very difficult.Conclusions. Pathological analysis of fatal outcomes among adult patients with HIV infection in a highly specialized hospital showed that in the vast majority of cases (70 % of our data) there was a combined or competing pathology as the main cause of death. Currently, the proportion of tuberculosis lesions as the main fatal disease has decreased, and fungal infections predominate. In the differential diagnosis of lung lesions in HIV-­associated diseases, there is an urgent needing to use a wide range of modern various methods of studying biological material in order to identify one or more etiological agents and adequately assess the activity of inflammatory changes caused by different pathogens., Цель работы — проанализировать истории болезни, данные клинико-лабораторных исследований и материалы аутопсий умерших в стационаре ВИЧ-инфицированных взрослых, оценить уровень совпадений и несоответствия клинического и патологоанатомического диагнозов.Материалы и методы. Проведено ретроспективное исследование летальных исходов в клинике Национального института фтизиатрии и пульмонологии имени Ф.Г. Яновского НАМН Украины с верифицированным диагнозом ВИЧ-инфекции за 5-летний период. Всего за указанный период умерло 157 лиц, из них 20 (12,7 %) с ВИЧ-инфекцией. Проанализирован ряд клинико-анамнестических данных и лабораторные показатели, приведенные в истории болезни пациентов, а также результаты макроскопического и микроскопического исследования при аутопсии согласно протоколам вскрытий. Выполнено сопоставление заключительного клинического и патологоанатомического диагнозов. Уста­новлена основная причина смерти в каждом случае. Учитывали стадию ВИЧ-инфекции на момент госпитализации пациентов и время ее выявления.Результаты и обсуждение. Среди всех умерших пациентов с ВИЧ-инфекцией наиболее частым диагнозом основного вторичного заболевания была пневмоцистная пневмония — 12 (60,0) % случаев, причем она достаточно часто (10 случаев (83,3 %)) сочеталась с другими инфекциями — грибковой, прижизненно не идентифицированной (2 случая), цитомегаловирусной инфекцией (4), микобактериозом (1), аспергиллезом (2), генерализованным туберкулезом (1). Только в 2 случаях без аутопсии был установлен диагноз пневмоцистной пневмонии без указания других значимых патологий легких. В остальных случаях диагностированы микобактериальная инфекция (5 случаев (25,0 %)), в том числе по 2 случая верифицированного туберкулеза, криптококковой инфекции, инвазивного аспергиллеза, гепатита С и грибковой инфекции без лабораторной верификации конкретного инфекта. Летальный исход произошел на стадии СПИДа при уровне CD4+­клеток < 250 кл./мкл. Количество случаев несо­ответствия заключительного клинического и патологоанатомического диагноза по результатам аутопсии составило 6 (54,5 %) из 11. В 5 случаях из 6 это было связано с развитием грибковой/микобактериальной инфекции. Практически у всех умерших больных было значительное количество как фоновых заболеваний, так и сопутствующей патологии, что весьма затрудняло их своевременную прижизненную диагностику.Выводы. Патологоанатомический анализ летальных исходов у взрослых пациентов с ВИЧ-ин­­фекцией в высокоспециализированном стационаре показал, что в 70 % случаев имела место сочетанная или конкурирующая патология как основная причина смерти. В настоящее время удельный вес туберкулезного поражения как основного смертельного заболевания уменьшился, а возросло количество грибковых инфекций. Для дифференциальной диагностики поражений легких при ВИЧ-ассоци­и­ро­ванных заболеваниях необходимо использовать широкий спектр современных методов исследования биологического материала для выявления одного или нескольких этиологических агентов и адекватной оценки активности воспалительных изменений, вызванных разными возбудителями., Мета роботи — проаналізувати історії хвороби, дані клініко-лабораторних досліджень та матеріали автопсій померлих у стаціонарі ВІЛ-інфікованих дорослих, оцінити рівень збігів і невідповідності клінічного та патологоанатомічного діагнозів.Матеріали та методи. Проведено ретроспективне дослідження летальних наслідків у клініці Національного інституту фтизіатрії і пульмонології імені Ф.Г. Яновського НАМН України з верифікованим діагнозом ВІЛ-інфекції за 5-річний період. Загалом за цей період часу померло 157 осіб, із них 20 (12,7 %) з ВІЛ-інфекцією. Проаналізовано низку клініко-анамнестичних та лабораторних показників, наведених в історії хвороби пацієнтів, а також результати макроскопічного і мікроскопічного дослідження при автопсії згідно із протоколами розтину. Виконано зіставлення остаточного клінічного та патологоанатомічного діагнозів. Установлено основну причину смерті в кожному випадку. Враховували стадію ВІЛ-інфекції на момент госпіталізації пацієнтів і час її виявлення.Результати та обговорення.Серед усіх померлих пацієнтів з ВІЛ-інфекцією найчастішим діагнозом основного вторинного захворювання була пневмоцистна пневмонія — 12 (60,0) % випадків, причому вона досить часто (10 випадків (83,3 %)) поєднувалася з іншими інфекціями — грибковою, прижиттєво не ідентифікованою (2 випадки), цитомегаловірусною інфекцією (4), мікобактеріозом (1), аспергільозом (2), генералізованим туберкульозом (1). Лише в 2 випадках без автопсії було встановлено діагноз пневмоцистної пневмонії без зазначення інших значущих хвороб легень. В інших випадках діагностовано мікобактеріальну інфекцію (5 випадків (25,0 %)), зокрема по 2 випадки верифікованого туберкульозу, криптококової інфекції, інвазивного аспергільозу, гепатиту С і грибкової інфекції без лабораторної верифікації конкретного збудника. Летальний наслідок відбувся на стадії СНІДу з рівнем CD4+­клітин < 250 кл./мкл. Кількість випадків невідповідності остаточного клінічного і патологоанатомічного діагнозів за результатами автопсії становила 6 (54,5 %) з 11 випадків. У 5 випадках із 6 це було пов’язано з розвитком грибкової/мікобактеріальної інфекції. Практично в усіх померлих хворих була значна кількість як фонових захворювань, так і супутньої патології, що значно утруднювало їх своєчасну прижиттєву діагностику.Висновки. Патологоанатомічний аналіз летальних наслідків у дорослих пацієнтів з ВІЛ-інфекцією у високоспеціалізованому стаціонарі показав, що у 70 % випадків мала місце поєднана або конкуруюча патологія як основна причина смерті. Нині питома вага туберкульозного ураження як основної смертельної хвороби зменшилася, а зросла кількість грибкових інфекцій. Для диференційної діагностики уражень легень при ВІЛ-асоційованих хворобах необхідно використовувати широкий спектр сучасних методів дослідження біологічного матеріалу для виявлення одного або кількох етіологічних чинників та адекватної оцінки активності запальних змін, спричинених різними збудниками.

Lung transplantation (LTx) can be a life saving treatment in end-stage pulmonary diseases, but survival after transplantation is still limited. Posttransplant development of chronic lung allograft dysfunction with bronchiolits obliterans syndrome (BOS) as the major subphenotype, is the main cause of morbidity and mortality. Early identification of high-risk patients for BOS is a large unmet clinical need. In this review, we discuss gene polymorphisms and gene expression related to the development of BOS.Candidate gene studies showed that donor and recipient gene polymorphisms affect transplant outcome and BOS-free survival after LTx. Both selective and nonselective gene expression studies revealed differentially expressed fibrosis and apoptosis-related genes in BOS compared with non-BOS patients. Significantly, recent microarray expression analysis of blood and broncho-alveolar lavage suggest a role for B-cell and T-cell responses prior to the development of BOS. Furthermore, 6 months prior to the development of BOS differentially expressed genes were identified in peripheral blood cells.Genetic polymorphisms and gene expression changes are associated with the development of BOS. Future genome wide studies are needed to identify easily accessible biomarkers for prediction of BOS toward precision medicine.

A Man with Progressive Dyspnea A 69-year-old man was evaluated at this hospital because of progressively worsening dyspnea. Results of chest imaging were consistent with fibrotic lung disease, and ...

The lung is a complex organ; it is both the initial barrier for inhaled agents and the site of metabolism and therapeutic effect for a subset of systemically administered drugs. Comprised of more than 40 cell types that are responsible for various important functions, the lung's complexity contributes to the subsequent challenges in developing complex in vitro co-culture models (also called microphysiological systems (MPS), complex in vitro models or organs-on-a-chip). Although there are multiple considerations and limitations in the development and qualification of such in vitro systems, MPS exhibit great promise in the fields of pharmacology and toxicology. Successful development and implementation of MPS models may enable mechanistic bridging between non-clinical species and humans, and increase clinical relevance of safety endpoints, while decreasing overall animal use. This article summarizes, from a biopharmaceutical industry perspective, essential elements for the development and qualification of lung MPS models. Its purpose is to guide MPS developers and manufacturers to expedite MPS utilization for safety assessment in the biopharmaceutical industry.