Longitudinal Follow-Up of Participants With Tobacco Exposure and Preserved Spirometry.

Importance: People who smoked cigarettes may experience respiratory symptoms without spirometric airflow obstruction. These individuals are typically excluded from chronic obstructive pulmonary disease (COPD) trials and lack evidence-based therapies. Objective: To define the natural history of persons with tobacco exposure and preserved spirometry (TEPS) and symptoms (symptomatic TEPS). Design, Setting, and Participants: SPIROMICS II was an extension of SPIROMICS I, a multicenter study of persons aged 40 to 80 years who smoked cigarettes (>20 pack-years) with or without COPD and controls without tobacco exposure or airflow obstruction. Participants were enrolled in SPIROMICS I and II from November 10, 2010, through July 31, 2015, and followed up through July 31, 2021. Exposures: Participants in SPIROMICS I underwent spirometry, 6-minute walk distance testing, assessment of respiratory symptoms, and computed tomography of the chest at yearly visits for 3 to 4 years. Participants in SPIROMICS II had 1 additional in-person visit 5 to 7 years after enrollment in SPIROMICS I. Respiratory symptoms were assessed with the COPD Assessment Test (range, 0 to 40; higher scores indicate more severe symptoms). Participants with symptomatic TEPS had normal spirometry (postbronchodilator ratio of forced expiratory volume in the first second [FEV1] to forced vital capacity >0.70) and COPD Assessment Test scores of 10 or greater. Participants with asymptomatic TEPS had normal spirometry and COPD Assessment Test scores of less than 10. Patient-reported respiratory symptoms and exacerbations were assessed every 4 months via phone calls. Main Outcomes and Measures: The primary outcome was assessment for accelerated decline in lung function (FEV1) in participants with symptomatic TEPS vs asymptomatic TEPS. Secondary outcomes included development of COPD defined by spirometry, respiratory symptoms, rates of respiratory exacerbations, and progression of computed tomographic-defined airway wall thickening or emphysema. Results: Of 1397 study participants, 226 had symptomatic TEPS (mean age, 60.1 [SD, 9.8] years; 134 were women [59%]) and 269 had asymptomatic TEPS (mean age, 63.1 [SD, 9.1] years; 134 were women [50%]). At a median follow-up of 5.76 years, the decline in FEV1 was -31.3 mL/y for participants with symptomatic TEPS vs -38.8 mL/y for those with asymptomatic TEPS (between-group difference, -7.5 mL/y [95% CI, -16.6 to 1.6 mL/y]). The cumulative incidence of COPD was 33.0% among participants with symptomatic TEPS vs 31.6% among those with asymptomatic TEPS (hazard ratio, 1.05 [95% CI, 0.76 to 1.46]). Participants with symptomatic TEPS had significantly more respiratory exacerbations than those with asymptomatic TEPS (0.23 vs 0.08 exacerbations per person-year, respectively; rate ratio, 2.38 [95% CI, 1.71 to 3.31], P < .001). Conclusions and Relevance: Participants with symptomatic TEPS did not have accelerated rates of decline in FEV1 or increased incidence of COPD vs those with asymptomatic TEPS, but participants with symptomatic TEPS did experience significantly more respiratory exacerbations over a median follow-up of 5.8 years.

Calcificaciones pulmonares metastásicas, 3 casos clínicos / Metastatic pulmonary calcifications: three clinical cases

Las calcificaciones pulmonares metastásicas, hacen referencia a una enfermedad metabólica, caracterizada por depósitos de calcio en tejido pulmonar sano. La etiología es amplia e incluye enfermedades malignas y benignas, siendo la falla renal la causa más frecuente. Es una condición, que, a pesar de ser frecuente, suele ser subdiagnosticada, por presentar pocos o ningún síntoma. Presentamos tres casos clínicos asociados a enfermedad renal crónica, pre y post trasplante.

Metastatic pulmonary calcifications refer to a metabolic disease, characterized by calcium deposits in healthy lung tissue. The etiology is broad and includes malignant and benign diseases, the kidney failure being the most frequent cause. It is a condition, which, despite being frequent, is usually underdiagnosed, because it presents few or no symptoms. We present three clinical cases associated with pre- and post-transplant kidney disease.

Associação entre comprometimento pulmonar, fatores de risco e desfechos em pacientes com covid-19 atendidos em hospital de referência na Paraíba / Association between lung involvement, risk factors and outcomes in COVID-19 patients treated at a reference hospital in Paraíba

Objetivo: Avaliar a associação entre o grau de comprometimento pulmonar (CP) na TC de tórax dos pacientes com COVID-19 com fatores de risco e desfechos. Métodos: Estudo observacional e retrospectivo com 284 pacientes com COVID-19. Avaliou-se idade, sexo, quadro clínico, saturação na admissão, fatores de risco, tempo de sinto-mas, porcentagem de CP, tempo de internação em enfermaria, UTI e de IOT, e óbito. Foram divididos três grupos conforme o grau de CP. Resultados: 167 pacientes possuíam comprometimento <25%; 80, 25-50%; e 37, >50%. O grupo com maior comprometimento pulmonar possuía maior idade, mais homens e maior presença de tosse, dispneia e alguma comorbidade. Também apresentou menor saturação à admissão, maior necessidade de IOT, in-ternação em enfermaria ou UTI e maior mortalidade. O CP, IOT e idade foram fatores preditores de mortalidade.Conclusões: O grau de CP aparenta estar significativamente associado a alguns parâmetros clínicos, necessidade de internação, intubação e óbito (AU)

Objective: To assess the association between the degree of lung involvement (LI) on chest CT scans of COVID-19 patients, risk factors and outcomes. Methods: Observational and retrospective study of 284 COVID-19 patients. Age, sex, clinical presentation, oxygen saturation on admission, risk factors, time after symptom onset, percentage of LI, length of stay in ward and ICU, duration of ETI, and death were assessed. 3 groups were created according to the LI. Results: 167 patients had an involvement of <25%; 80, 25-50%; and 37, >50%. The group with gre-ater LI was older, had more males and a higher incidence of cough, dyspnea and some comorbidity. Moreover, the group with greater LI had lower saturation on admission, more ETI, more admissions to the ward or ICU, and higher mortality. LI, ETI and age were predictors of mortality. Conclusion: The degree of LI appears to be significantly associated with some clinical parameters, need for hospitalization, intubation, and death (AU)

Acute Dyspnea and Hemoptysis in an 84-Year-Old Man With Multiple Comorbidities.

CASE PRESENTATION: An 84-year-old man with an active smoking habit presented to the ED with dyspnea, hemoptysis, and thick phlegm that was difficult to clear. He reported no weight loss, no fever, and no chest pain or dysphonia. He denied both international travel and previous contact with confirmed cases of TB or SARS-CoV-2. He had no known occupational exposures. The patient's personal history included a resolved complete atrioventricular block that required a permanent pacemaker, moderate-to-severe COPD, rheumatoid arthritis (treated with oral prednisone, 2.5 mg/d) and B-chronic lymphocytic leukemia (treated with methotrexate and prophylactic oral supplements of ferrous sulfate). Moreover, he was in medical follow up because of a peptic ulcer, atrophic gastritis, and colonic diverticulosis. The patient also had a history of thoracic surgery after an episode of acute mediastinitis from an odontogenic infection, which required ICU management and temporal tracheostomy.

Pulmonary health effects of wintertime particulate matter from California and China following repeated exposure and cessation.

Epidemiological studies show strong associations between fine particulate matter (PM2.5) air pollution and adverse pulmonary effects. In the present study, wintertime PM2.5 samples were collected from three geographically similar regions-Sacramento, California, USA; Jinan, Shandong, China; and Taiyuan, Shanxi, China-and extracted to form PMCA, PMSD, and PMSX, respectively, for comparison in a BALB/c mouse model. Each of four groups was oropharyngeally administered Milli-Q water vehicle control (50 µL) or one type of PM extract (20 µg/50 µL) five times over two weeks. Mice were necropsied on post-exposure days 1, 2, and 4 and examined using bronchoalveolar lavage (BAL), histopathology, and assessments of cytokine/chemokine mRNA and protein expression. Chemical analysis demonstrated all three extracts contained black carbon, but PMSX contained more sulfates and polycyclic aromatic hydrocarbons (PAHs) associated with significantly greater neutrophil numbers and greater alveolar/bronchiolar inflammation on post-exposure days 1 and 4. On day 4, PMSX-exposed mice also exhibited significant increases in interleukin-1 beta, tumor necrosis factor-alpha, and chemokine C-X-C motif ligands-3 and -5 mRNA, and monocyte chemoattractant protein-1 protein. These combined findings suggest greater sulfate and PAH content contributed to a more intense and progressive inflammatory response with repeated PMSX compared to PMCA or PMSD exposure.

Comparison of biosimilar Tigerase and Pulmozyme in long-term symptomatic therapy of patients with cystic fibrosis and severe pulmonary impairment (subgroup analysis of a Phase III randomized open-label clinical trial (NCT04468100)).

BACKGROUND: Patients with cystic fibrosis (CF) need costly medical care and adequate therapy with expensive medicinal products. Tigerase® is the first biosimilar of dornase alfa, developed by the lead Russian biotechnology company GENERIUM. The aim of the manuscript to present post hoc sub-analysis of patients' data with cystic fibrosis and severe pulmonary impairment of a larger comparative study (phase III open label, prospective, multi-centre, randomized study (NCT04468100)) of a generic version of recombinant human DNase Tigerase® to the only comparable drug, Pulmozyme®. METHODS: In the analyses included subgroup of 46 severe pulmonary impairment patients with baseline FEV1 level 40-60% of predicted (23 patients in each treatment group) out of 100 patients registered in the study phase III open label, prospective, multi-center, randomized study (NCT04468100), and compared efficacy endpoints (FEV1, FVC, number and time of exacerbations, body weight, St.George's Respiratory Questionnaire) as well as safety parameters (AEs, SAEs, anti-drug antibody) within 24 treatment weeks. RESULTS: All outcomes were comparable among the studied groups. In the efficacy dataset, the similar mean FEV1 and mean FVC changes for 24 weeks of both treatment groups were observed. The groups were also comparable in safety, all the secondary efficacy parameters and immunogenicity. CONCLUSIONS: The findings from this study support the clinical Tigerase® biosimilarity to Pulmozyme® administered in CF patients with severe impairment of pulmonary function.

Association Between Preserved Ratio Impaired Spirometry and Clinical Outcomes in US Adults.

Importance: Chronic lung diseases are a leading cause of morbidity and mortality. Unlike chronic obstructive pulmonary disease, clinical outcomes associated with proportional reductions in expiratory lung volumes without obstruction, otherwise known as preserved ratio impaired spirometry (PRISm), are poorly understood. Objective: To examine the prevalence, correlates, and clinical outcomes associated with PRISm in US adults. Design, Setting, and Participants: The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study was a retrospective study with harmonized pooled data from 9 US general population-based cohorts (enrollment, 65 251 participants aged 18 to 102 years of whom 53 701 participants had valid baseline lung function) conducted from 1971-2011 (final follow-up, December 2018). Exposures: Participants were categorized into mutually exclusive groups by baseline lung function. PRISm was defined as the ratio of forced expiratory volume in the first second to forced vital capacity (FEV1:FVC) greater than or equal to 0.70 and FEV1 less than 80% predicted; obstructive spirometry FEV1:FVC ratio of less than 0.70; and normal spirometry FEV1:FVC ratio greater than or equal to 0.7 and FEV1 greater than or equal to 80% predicted. Main Outcomes and Measures: Main outcomes were all-cause mortality, respiratory-related mortality, coronary heart disease (CHD)-related mortality, respiratory-related events (hospitalizations and mortality), and CHD-related events (hospitalizations and mortality) classified by adjudication or validated administrative criteria. Absolute risks were adjusted for age and smoking status. Poisson and Cox proportional hazards models comparing PRISm vs normal spirometry were adjusted for age, sex, race and ethnicity, education, body mass index, smoking status, cohort, and comorbidities. Results: Among all participants (mean [SD] age, 53.2 [15.8] years, 56.4% women, 48.5% never-smokers), 4582 (8.5%) had PRISm. The presence of PRISm relative to normal spirometry was significantly associated with obesity (prevalence, 48.3% vs 31.4%; prevalence ratio [PR], 1.68 [95% CI, 1.55-1.82]), underweight (prevalence, 1.4% vs 1.0%; PR, 2.20 [95% CI, 1.72-2.82]), female sex (prevalence, 60.3% vs 59.0%; PR, 1.07 [95% CI, 1.01-1.13]), and current smoking (prevalence, 25.2% vs 17.5%; PR, 1.33 [95% CI, 1.22-1.45]). PRISm, compared with normal spirometry, was significantly associated with greater all-cause mortality (29.6/1000 person-years vs 18.0/1000 person-years; difference, 11.6/1000 person-years [95% CI, 10.0-13.1]; adjusted hazard ratio [HR], 1.50 [95% CI, 1.42-1.59]), respiratory-related mortality (2.1/1000 person-years vs 1.0/1000 person-years; difference, 1.1/1000 person-years [95% CI, 0.7-1.6]; adjusted HR, 1.95 [95% CI, 1.54-2.48]), CHD-related mortality (5.4/1000 person-years vs 2.6/1000 person-years; difference, 2.7/1000 person-years [95% CI, 2.1-3.4]; adjusted HR, 1.55 [95% CI, 1.36-1.77]), respiratory-related events (12.2/1000 person-years vs 6.0/1000 person-years; difference, 6.2/1000 person-years [95% CI, 4.9-7.5]; adjusted HR, 1.90 [95% CI, 1.69-2.14]), and CHD-related events (11.7/1000 person-years vs 7.0/1000 person-years; difference, 4.7/1000 person-years [95% CI, 3.7-5.8]; adjusted HR, 1.30 [95% CI, 1.18-1.42]). Conclusions and Relevance: In a large, population-based sample of US adults, baseline PRISm, compared with normal spirometry, was associated with a small but statistically significant increased risk for mortality and adverse cardiovascular and respiratory outcomes. Further research is needed to explore whether this association is causal.

Restrictive Pulmonary Dysfunction May Increase Blood Loss During Liver Resection.

BACKGROUND: Restrictive pulmonary dysfunction (RPD) is a risk factor for perioperative complications during gastrointestinal surgery. We hypothesized that high airway pressure due to RPD results in increased intraoperative blood loss during liver surgery. Thus, we investigated the effects of RPD on perioperative outcomes for liver resection. METHODS: This study included 496 patients who underwent curative liver resection at our hospital between April 2009 and April 2020. Perioperative outcomes for the RPD and control groups were compared. Restrictive pulmonary dysfunction was defined as % vital capacity <80%. RESULTS: Forty-one patients (8.3%) had RPD. No significant differences were observed in intraoperative blood losses (440 mL vs 320 mL, P = .340), overall complication rates (29.3% vs 31.2%, P = .797), or pulmonary complication rates (4.9% vs 9.0%, P = .286) between the RPD and control groups. In the 256 patients who underwent anatomical liver resection, 18 patients (7.0%) had RPD. The intraoperative blood loss was significantly higher in the RPD group (925 mL vs 456 mL, P = .013), but no differences in the overall complication rates (44.4% vs 37.3%, P = .528) or pulmonary complication rates (11.1% vs 10.5%, P = .589) between the two groups were detected. A multivariate analysis showed that RPD was an independent risk factor for intraoperative blood loss ≥500 mL during anatomical liver resection (odds ratio 4.132; 95% confidence interval 1.135-15.045; P = .031). DISCUSSION: Restrictive pulmonary dysfunction may be a risk factor for intraoperative blood loss during anatomical liver resection, which requires exposure of the main hepatic vein.

A cellular census of human peripheral immune cells identifies novel cell states in lung diseases.

Increasing evidence supports a central role of the immune system in lung diseases. Understanding how immunological alterations between lung diseases provide opportunities for immunotherapy. Exhausted T cells play a key role of immune suppression in lung cancer and chronic obstructive pulmonary disease was proved in our previous study. The present study aims to furthermore define molecular landscapes and heterogeneity of systemic immune cell target proteomic and transcriptomic profiles and interactions between circulating immune cells and lung residential cells in various lung diseases. We firstly measured target proteomic profiles of circulating immune cells from healthy volunteers and patients with stable pneumonia, stable asthma, acute asthma, acute exacerbation of chronic obstructive pulmonary disease, chronic obstructive pulmonary disease and lung cancer, using single-cell analysis by cytometry by time-of-flight with 42 antibodies. The nine immune cells landscape was mapped among those respiratory system diseases, including CD4+ T cells, CD8+ T cells, dendritic cells, B cells, eosinophil, γδT cells, monocytes, neutrophil and natural killer cells. The double-negative T cells and exhausted CD4+ central memory T cells subset were identified in patients with acute pneumonia. This T subset expressed higher levels of T-cell immunoglobulin and mucin domain-containing protein 3 (Tim3) and T-cell immunoreceptor with Ig and ITIM domains (TIGIT) in patients with acute pneumonia and stable pneumonia. Biological processes and pathways of immune cells including immune response activation, regulation of cell cycle and pathways in cancer in peripheral blood immune cells were defined by bulk RNA sequencing (RNA-seq). The heterogeneity among immune cells including CD4+ , CD8+ T cells and NK T cells by single immune cell RNA-seq with significant difference was found by single-cell sequencing. The effect of interstitial telocytes on the immune cell types and immune function was finally studied and the expressions of CD8a and chemokine C-C motif receptor 7 (CCR7) were increased significantly in co-cultured groups. Our data indicate that proteomic and transcriptomic profiles and heterogeneity of circulating immune cells provides new insights for understanding new molecular mechanisms of immune cell function, interaction and modulation as a source to identify and develop biomarkers and targets for lung diseases.

18F-FDG PET/CT imaging in the diagnosis of drug-induced lung disease and pulmonary infection in lymphoma.

OBJECTIVE: Lymphoma is a hematological disease with high prevalence. Multi-cycle chemotherapy (CHT) or local radiotherapy is applied usually; however, adverse events have been reported, such as drug-induced lung disease (DILD). Positron emission tomography/computed tomography (PET/CT) is often used to evaluate the lesion, treatment effect, and prognosis of lymphoma. We investigated DILD and pulmonary infection (PI) after multi-cycle CHT in lymphoma patients, to identify DILD and PI, provide guidance for later treatment for them. METHODS: In all, 677 patients diagnosed with lymphoma and who underwent CHT were included. These patients underwent 18fluorodeoxyglucose (18F-FDG) PET/CT before and after CHT at Shandong Cancer Hospital (affiliated with Shandong University) between April 2015 and November 2019. Fifty patients developed DILD, 41 patients had lung infections; lesion characteristics were analyzed based on clinical characteristics, laboratory examinations, and PET/CT imaging. RESULTS: Among the 677 lymphoma patients, there were 50 cases of DILD, with an incidence rate of 7.4%. PET/CT showed an elevated 18fluorodeoxyglucose uptake lung background, septal thickening and reticulation, multiple ground glass-like shadows, and grid-shaped blur shadows, which were more common in the lung periphery and under the pleura. The maximum standardized uptake value in the lung was 2.45 ±â€Š0.52. Pulmonary infections occurred in 41 patients, and the maximum standardized uptake value was 4.05 ±â€Š1.42. Age, sex, CHT cycle, Ann-Arbor stage, and lymphocyte levels were not significantly different between DILD and PI patients. Leukocyte and neutrophils showed significant differences; the PI patients had increased laboratory indexes of leukocyte and neutrophils. The mean number of CHT cycles was 4 cycles for DILD and PI. CONCLUSIONS: PET/CT imaging has high sensitivity and detection rates for primary and metastatic lymphoma lesions. DILD mostly occurs in the middle and late stages of CHT. Laboratory tests and PET/CT can evaluate the lesions and treatment effects, and provide guidance for subsequent treatment plans for patients.

Breastfeeding in Cystic Fibrosis: A Systematic Review on Prevalence and Potential Benefits.

Breastfeeding (BF) is considered the normative standard of feeding for all infants. However, the impact of BF in patients with cystic fibrosis (CF) is not completely defined. Therefore, we conducted a systematic review to evaluate BF prevalence in the CF population and its impact on anthropometric and pulmonary outcomes. We searched MEDLINE, Embase and the Cochrane Library for original articles published in English up to 4 December 2020 that report the prevalence of BF and/or any measure of association between BF and anthropometric or pulmonary outcomes. Nine observational studies were identified (six retrospective cohort studies, one prospective cohort study, one survey and one case-control study within a retrospective cohort). The BF rate in CF patients is lower than that of the healthy population (approximately 50-60% of infants were breastfed at any time). The benefits in anthropometric outcomes of BF for >2 months in this at-risk population are unclear. A few relatively small studies suggest a potential benefit of BF in reducing lung infections, although data are inconsistent. The currently available data are insufficient to draw definite conclusions on the benefits of exclusive BF in anthropometric and pulmonary outcomes in CF. Clinical trials evaluating well-defined BF promotion interventions are needed.

Basal epithelial stem cells cross an alarmin checkpoint for postviral lung disease.

Epithelial cells are charged with protection at barrier sites, but whether this normally beneficial response might sometimes become dysfunctional still needs definition. Here, we recognized a pattern of imbalance marked by basal epithelial cell growth and differentiation that replaced normal airspaces in a mouse model of progressive postviral lung disease due to the Sendai virus. Single-cell and lineage-tracing technologies identified a distinct subset of basal epithelial stem cells (basal ESCs) that extended into gas-exchange tissue to form long-term bronchiolar-alveolar remodeling regions. Moreover, this cell subset was selectively expanded by crossing a cell-growth and survival checkpoint linked to the nuclear-localized alarmin IL-33 that was independent of IL-33 receptor signaling and instead connected to autocrine chromatin accessibility. This mechanism creates an activated stem-progenitor cell lineage with potential for physiological or pathological function. Thus, conditional loss of Il33 gene function in basal epithelial cells disrupted the homeostasis of the epithelial barrier at skin and gut sites but also markedly attenuated postviral disease in the lung based on the downregulation of remodeling and inflammation. Thus, we define a basal ESC strategy to deploy innate immune machinery that appears to overshoot the primordial goal of self-defense. Our findings reveal new targets to stratify and correct chronic and often deadly postviral disease.

Telemonitoring of daily activities compared to the six-minute walk test further completes the puzzle of oximetry-guided interventions.

Pulmonary rehabilitation is based on a thorough patient assessment, including peripheral oxygen saturation (SpO2) and heart rate (HR) at rest and on exertion. To understand whether exercise-field tests identify patients who desaturate (SpO2 < 90%) during physical activities, this study compared the six-minute walk test (6MWT) and daily-life telemonitoring. Cross-sectional study including 100 patients referred for pulmonary rehabilitation. The 6MWT was performed in hospital with continuous assessment of SpO2, HR, walked distance and calculated metabolic equivalent of tasks (METs). Patients were also evaluated in real-life by SMARTREAB telemonitoring, a combined oximetry-accelerometery with remote continuous assessment of SpO2, HR and METs. SMARTREAB telemonitoring identified 24% more desaturators compared with the 6MWT. Moreover, there were significant mean differences between 6MWT and SMARTREAB in lowest SpO2 of 7.2 ± 8.4% (P < 0.0005), in peak HR of - 9.3 ± 15.5% (P < 0.0005) and also in activity intensity of - 0.3 ± 0.8 METs (P < 0.0005). The 6MWT underestimates the proportion of patients with exercise-induced oxygen desaturation compared to real-life telemonitoring. These results help defining oximetry-guided interventions, such as telemedicine algorithms, oxygen therapy titration and regular physical activity assessment in pulmonary rehabilitation.

Lymphopenia in hospitalized patients and its relationship with severity of illness and mortality.

BACKGROUND: Lymphopenia is associated with various pathologies such as sepsis, burns, trauma, general anesthesia and major surgeries. All these pathologies are clinically expressed by the so-called Systemic Inflammatory Response Syndrome which does not include lymphopenia into defining criteria. The main objective of this work was to analyze the diagnosis of patients admitted to a hospital related to lymphopenia during hospital stay. In addition, we investigated the relationship of lymphopenia with the four levels of the Severity of Illness (SOI) and the Risk of Mortality (ROM). METHOD AND FINDINGS: Lymphopenia was defined as Absolute Lymphocyte Count (ALC) <1.0 x109/L. ALC were analyzed every day since admission. The four levels (minor, moderate, major and extreme risk) of both SOI and ROM were assessed. A total of 58,260 hospital admissions were analyzed. More than 41% of the patients had lymphopenia during hospital stay. The mean time to death was shorter among patients with lymphopenia on admission 65.6 days (CI95%, 57.3-73.8) vs 89.9 (CI95%, 82.4-97.4), P<0.001. Also, patients with lymphopenia during hospital stay had a shorter time to the mortality, 67.5 (CI95%, 61.1-73.9) vs 96.9 (CI95%, 92.6-101.2), P<0.001. CONCLUSIONS: Lymphopenia had a high prevalence in hospitalized patients with greater relevance in infectious pathologies. Lymphopenia was related and clearly predicts SOI and ROM at the time of admission, and should be considered as clinical diagnostic criteria to define SIRS.

Airway-On-A-Chip: Designs and Applications for Lung Repair and Disease.

The lungs are affected by illnesses including asthma, chronic obstructive pulmonary disease, and infections such as influenza and SARS-CoV-2. Physiologically relevant models for respiratory conditions will be essential for new drug development. The composition and structure of the lung extracellular matrix (ECM) plays a major role in the function of the lung tissue and cells. Lung-on-chip models have been developed to address some of the limitations of current two-dimensional in vitro models. In this review, we describe various ECM substitutes utilized for modeling the respiratory system. We explore the application of lung-on-chip models to the study of cigarette smoke and electronic cigarette vapor. We discuss the challenges and opportunities related to model characterization with an emphasis on in situ characterization methods, both established and emerging. We discuss how further advancements in the field, through the incorporation of interstitial cells and ECM, have the potential to provide an effective tool for interrogating lung biology and disease, especially the mechanisms that involve the interstitial elements.

Patient with H syndrome, cardiogenic shock, multiorgan infiltration, and digital ischemia.

BACKGROUND: H syndrome (HS) is a rare autoinflammatory disease caused by a mutation in the solute carrier family 29, member 3 (SCL29A3) gene. It has a variable clinical presentation and little phenotype-genotype correlation. The pathognomonic sign of HS is cutaneous hyperpigmentation located mainly in the inner thighs and often accompanied by other systemic manifestations. Improvement after tocilizumab treatment has been reported in a few patients with HS. We report the first patient with HS who presented cardiogenic shock, multiorgan infiltration, and digital ischemia. CASE PRESENTATION: 8-year-old boy born to consanguineous parents of Moroccan origin who was admitted to the intensive care unit during the Coronavirus Disease-2019 (COVID-19) pandemic with tachypnoea, tachycardia, and oliguria. Echocardiography showed dilated cardiomyopathy and severe systolic dysfunction compatible with cardiogenic shock. Additionally, he presented with multiple organ dysfunction syndrome. SARS-CoV-2 polymerase chain reaction (PCR) and antibody detection by chromatographic immunoassay were negative. A previously ordered gene panel for pre-existing sensorineural hearing loss showed a pathological mutation in the SCL29A3 gene compatible with H syndrome. Computed tomography scan revealed extensive alveolar infiltrates in the lungs and multiple poor defined hypodense lesions in liver, spleen, and kidneys; adenopathy; and cardiomegaly with left ventricle subendocardial nodules. Invasive mechanical ventilation, broad antibiotic and antifungal coverage showed no significant response. Therefore, Tocilizumab as compassionate use together with pulsed intravenous methylprednisolone was initiated. Improvement was impressive leading to normalization of inflammation markers, liver and kidney function, and stabilising heart function. Two weeks later, he was discharged and has been clinically well since then on two weekly administration of Tocilizumab. CONCLUSIONS: We report the most severe disease course produced by HS described so far in the literature. Our patient's manifestations included uncommon, new complications such as acute heart failure with severe systolic dysfunction, multi-organ cell infiltrate, and digital ischemia. Most of the clinical symptoms of our patient could have been explained by SARS-CoV-2, demonstrating the importance of a detailed differential diagnosis to ensure optimal treatment. Although the mechanism of autoinflammation of HS remains uncertain, the good response of our patient to Tocilizumab makes a case for the important role of IL-6 in this syndrome and for considering Tocilizumab as a first-line treatment, at least in severely affected patients.

Flexible bronchoscopy in Ghana: initial experience in a tertiary hospital.

INTRODUCTION: the use of flexible bronchoscopy in developing countries is limited. We report our initial experience and outcome with the use of flexible bronchoscopy at the Tamale Teaching Hospital in Ghana. This is the first reported case series of flexible bronchoscopy in Ghana. METHODS: a retrospective review of patients who had flexible bronchoscopy from 2017-2019 was analyzed. Patient demographics and outcomes were summarized using frequency distribution and percentages. RESULTS: we performed flexible bronchoscopies in 33 patients with mean age of 43 years. All patients were symptomatic at the time of presentation with the most common symptoms being chest pain (63.6%), dyspnea (57.6%) and cough (48.5%). The indication for bronchoscopy in most of the cases were suspected malignancy in 16 (48.5%) followed by infection 9 (27.3%), trauma 4 (12.1%) and others 4 (12.1%). We observed abnormal bronchoscopic findings in 25 (75.8%) of the cases with most of the pathologies in the right main bronchus. Twelve patients had toilet bronchoscopy, 6 had biopsy, 5 had no intervention and 4 patients had bronchoalveolar lavage (BAL). Culture and sensitivity results were available for 11 patients, of which 7 patients had negative results. Thirteen (13) malignancies and 11 inflammatory/infectious diseases were diagnosed in this case series. The mean procedure time was 32 minutes with mean hospital stay of 7 days. There was no complication or mortality in our series. Conclusion: flexible bronchoscopy is a safe procedure and indispensable in Ghana where there is an increasing incidence of lung diseases.

A 44-Year-Old Woman With Multiple Neoplasms and Cystic Lung Disease.

CASE PRESENTATION: A 44-year-old woman with a history of renal cell carcinoma and thyroid cancer was referred to our institution for evaluation of cystic lung disease. She was an active smoker with a 15-pack-year of tobacco use. Two years before her presentation, she underwent a left nephrectomy for renal cell carcinoma, clear cell type. Four months before, she had a total thyroidectomy that showed nodules consistent with noninvasive follicular thyroid neoplasm with papillary like nuclear features. She had no previous pulmonary complaints. Her family history was positive for breast cancer in her grandmother. There was no family history of pneumothorax. She complained of mild shortness of breath with exertion and occasional nonproductive cough. As part of her oncologic work up, she underwent a chest CT scan of the lungs (Fig 1).