Clinical and functional status of patients with severe COVID-19 pneumonia: an observational study at 2-3 months following discharge.

Introduction: Critically ill COVID-19 patients present long-term sequelae that affect their everyday life. This study aimed to describe the clinical and functional status of patients with severe COVID-19 pneumonia at 2-3 months post discharge from a Spanish critical care unit. Methods: We collected retrospective data from 58 patients admitted to the critical care unit with diagnosis of severe respiratory failure due to COVID-19. Only patients who required invasive (IMV) or noninvasive ventilation (NIV) during their hospital stay were included. The following data were collected 2-3 months after hospital discharge: respiratory signs and symptoms, lung ultrasound (LUS) and diaphragm ultrasound images, blood test analysis, lung function parameters (spirometry and DLCO), exercise capacity (6 min walk test and sit-to-stand test), level of physical activity and health-related quality of life. Results: We found clinical symptoms and lung structural alterations in LUS images of 26 patients (48.1%). Those presenting LUS abnormalities had longer length of stay in hospital (p = 0.026), functional alterations in spirometry (p < 0.01) and decreased diaphragm excursion (p = 0.029). No significant alterations were observed in blood test analysis, exercise capacity, level of physical activity and health-related quality of life. Conclusions: A significant part of the patients admitted to a critical care unit continue to present clinical symptoms, pulmonary morphological abnormalities, and lung function alterations 2-3 months post discharge. This study corroborates that assessing the functional status of the survivors is essential to monitor the evolution of pulmonary sequelae.

How did the COVID-19 pandemic affect urinary incontinence and its management in the nursing homes? A descriptive phenomenological study.

BACKGROUND: Management of urinary incontinence (UI) in nursing homes (NHs) represents a complex process that may have become more challenging during a period in which front-line health professionals (HPs) must deal with the outbreak of a new infectious disease. We aimed to investigate how UI and its management was affected in NHs during the COVID-19 pandemic based on the perception of health professionals. METHODS: This qualitative study was conducted between January and March 2021 with 16 health professionals working in nine NHs in the Osona county (Barcelona, Spain) during the COVID-19 pandemic. The individual interviews were conducted via online videoconferencing and each session was audio recorded. RESULTS: The HPs highlighted that the COVID-19 pandemic affected the management of continence in NHs, resulting in increased UI. Two main factors were identified: workforce-related and resident-related factors. Considering the workforce, three main topics emerged: pandemic as the priority, lack of personnel and use of personal protective equipment as an obstacle to communication with residents and attending to their needs. CONCLUSION: Managing UI in NHs always has been a challenging point of care, and these challenges were worsened by the restrictions and additional difficulties that arose during the COVID-19 pandemic.

Incidence and Predictive Factors of Functional Decline in Older People Living in Nursing Homes: A Systematic Review.

OBJECTIVES: To review the evidence on incidence and predictive factors of functional decline (FD) in nursing home (NH) residents. DESIGN: A systematic review of the literature. SETTING AND PARTICIPANTS: Longitudinal studies involving individuals age 60 years and older living in a NH and with at least 2 functional capacity assessments were eligible. METHODS: The search was carried out up to June 2021 and was conducted in Embase, PubMed, Web of Science, Cochrane Library, CINAHL, Scopus, SciELO, and Google Scholar databases. RESULTS: A total of 27 studies met the eligibility criteria, most of which were prospective, recruiting participants in more than 1 NH, and conducted in a single country. Studies reported a high rate of functional dependency at baseline and FD at follow-up; in 1 year, 38.9% to 50.6% of residents experienced FD. Predictive factors of FD that were significant in at least 2 of the included studies were cognitive impairment, functional status at baseline, urinary incontinence, length of institutionalization, age, depression, being married, being male, and stroke disease. Protective factors were licensed nursing hours and presence of a geriatrician within the NH staff. CONCLUSIONS AND IMPLICATIONS: This review highlights the high incidence of FD in NH residents and identifies risk and protective factors of FD that may support the design of preventative strategies for this vulnerable and frail population.

Early Life Microbial Exposure and Immunity Training Effects on Asthma Development and Progression.

Asthma is the most common inflammatory disease affecting the lungs, which can be caused by intrauterine or postnatal insults depending on the exposure to environmental factors. During early life, the exposure to different risk factors can influence the microbiome leading to undesired changes to the immune system. The modulations of the immunity, caused by dysbiosis during development, can increase the susceptibility to allergic diseases. On the other hand, immune training approaches during pregnancy can prevent allergic inflammatory diseases of the airways. In this review, we focus on evidence of risk factors in early life that can alter the development of lung immunity associated with dysbiosis, that leads to asthma and affect childhood and adult life. Furthermore, we discuss new ideas for potential prevention strategies that can be applied during pregnancy and postnatal period.

Emerging Cell-Based Therapies in Chronic Lung Diseases: What About Asthma?

Asthma is a widespread disease characterized by chronic airway inflammation. It causes substantial disability, impaired quality of life, and avoidable deaths around the world. The main treatment for asthmatic patients is the administration of corticosteroids, which improves the quality of life; however, prolonged use of corticosteroids interferes with extracellular matrix elements. Therefore, cell-based therapies are emerging as a novel therapeutic contribution to tissue regeneration for lung diseases. This study aimed to summarize the advancements in cell therapy involving mesenchymal stromal cells, extracellular vesicles, and immune cells such as T-cells in asthma. Our findings provide evidence that the use of mesenchymal stem cells, their derivatives, and immune cells such as T-cells are an initial milestone to understand how emergent cell-based therapies are effective to face the challenges in the development, progression, and management of asthma, thus improving the quality of life.

Biomechanical Response of Lung Epithelial Cells to Iron Oxide and Titanium Dioxide Nanoparticles.

Increasing evidence shows that lungs can be damaged by inhalation of nanoparticles (NPs) at environmental and occupational settings. Recent findings have associated the exposure to iron oxide (Fe2O3) and titanium dioxide (TiO2) - NPs widely used in biomedical and clinical research - with pulmonary oxidative stress and inflammation. Although changes on cellular mechanics could contribute to pulmonary inflammation, there is no information regarding the effects of Fe2O3 and TiO2 on alveolar epithelial cell biomechanics. The aim was to investigate the NPs-induced biomechanical effects in terms of cell stiffness and traction forces exerted by human alveolar epithelial cells. Cell Young's modulus (E) measured by atomic force microscopy in alveolar epithelial cells significantly decreased after exposure to Fe2O3 and TiO2 (∼28 and ∼25%, respectively) compared to control conditions. Moreover, both NPs induced a similar reduction in the traction forces exerted by the alveolar epithelial cells in comparison to the control conditions. Accordingly, immunofluorescence images revealed a reduction of actomyosin stress fibers in response to the exposure to NPs. However, no inflammatory response was detected. In conclusion, an acute exposure of epithelial pulmonary cells to Fe2O3 and TiO2 NPs, which was mild since it was non-cytotoxic and did not induce inflammation, modified cell biomechanical properties which could be translated into damage of the epithelial barrier integrity, suggesting that mild environmental inhalation of Fe2O3 and TiO2 NPs could not be innocuous.

Escherichia coli lipopolysaccharide induces alveolar epithelial cell stiffening.

INTRODUCTION: Application of lipopolysaccharide (LPS) is a widely employed model to mimic acute respiratory distress syndrome (ARDS). Available data regarding LPS-induced biomechanical changes on pulmonary epithelial cells are limited only to P. aeruginosa LPS. Considering that LPS from different bacteria could promote a specific mechanical response in epithelial cells, we aim to assess the effect of E. coli LPS, widely employed as a model of ARDS, in the biomechanics of alveolar epithelial cells. METHODS: Young's modulus (E) of alveolar epithelial cells (A549) was measured by atomic force microscopy every 5 min throughout 60 min of experiment after treatment with LPS from E. coli (100 µg/mL). The percentage of cells presenting actin stress fibers (F-actin staining) was also evaluated. Control cells were treated with culture medium and the values obtained were compared with LPS-treated cells for each time-point. RESULTS: Application of LPS induced significant increase in E after 20 min (77%) till 60 min (104%) in comparison to controls. Increase in lung epithelial cell stiffness induced by LPS was associated with a higher number of cells presenting cytoskeletal remodeling. CONCLUSIONS: The observed effects of E. coli LPS on alveolar epithelial cells suggest that this widely-used LPS is able to promote a quick formation of actin stress fibers and stiffening cells, thereby facilitating the disruption of the pulmonary epithelial barrier.

Lung and liver responses to 1- and 7-day treatments with LASSBio-596 in mice subchronically intoxicated by microcystin-LR.

Microcystin-LR (MC-LR) can cause serious injuries upon short- and long-term exposures that can be prevented by LASSBio-596 (LB-596), an anti-inflammatory compound. We aimed to test LB-596 following subchronic exposure to MC-LR. Swiss mice received 10 intraperitoneal injections of distilled water (DW) or MC-LR (20 µg/kg bw) every 2 days. On the 10th injection animals receiving DW were gavaged with DW or 50 mg/kg bw of LB-596 for 1 or 7 days (C1D, C7D, CL1D and CL7D groups), whereas those exposed to MC-LR received either DW or 50 mg/kg of LB-596 for 1 or 7 days (T1D, T7D, TL1D and TL7D groups). Twelve hours after the last gavage we assessed respiratory mechanics, and extracted lung and liver for histology, apoptosis, inflammatory biomarkers and MC-LR content. C1D, C7D, CL1D and CL7D were all similar. Mechanical parameters were significantly higher in T1D and T7D compared to the other groups. LB-596 reversed these changes on day 1 of administration. LB-596 reduced inflammatory mediators in lung and liver on day 1 of treatment. On day 7 apoptosis in liver and lung fell even more. Briefly, 7-day administration completely reversed lung and liver changes.

Time-dependency of mice lung recovery after a 4-week exposure to traffic or biomass air pollutants.

The time-dependency of lung recovery after 3 intranasal instillations per week during four weeks of distilled water (C groups) or particles (15µg) from traffic (U groups) or biomass burning (B groups) was observed in BALB/c mice. Lung mechanics [static elastance (Est), viscoelastic component of elastance (ΔE), lung resistive (ΔP1) and viscoelastic/inhomogeneous (ΔP2) pressures] and histology were analyzed 1 (C1, U1, B1), 2 (C2, U2, B2), 7 (C7, U7, B7) or 14 days (C14, U14, B14) after the last instillation. Est, ΔE, ΔP1 and ΔP2 were higher in U1 and B1 than in C1, returning to control values at day 2, except for ΔP1 that normalized after 7 days. Alveolar collapse, bronchoconstriction index and alveolar lesion were larger in U1 and B1 than in C1, however collapse returned to baseline at 7 days, while the others normalized in 2 days. A 4-week exposure to U and B induced lung impairment that resolved 7 days after the last exposure.

Pulmonary and hepatic injury after sub-chronic exposure to sublethal doses of microcystin-LR.

We had previously shown that microcystin-LR (MCLR) could induce lung and liver inflammation after acute exposure. The biological outcomes following prolonged exposure to MCLR, although more frequent, are still poorly understood. Thus, we aimed to verify whether repeated doses of MCLR could damage lung and liver and evaluate the dose-dependence of the results. Male Swiss mice received 10 intraperitoneal injections (i.p.) of distilled water (60 µL, CTRL) or different doses of MCLR (5 µg/kg, TOX5), 10 µg/kg (TOX10), 15 µg/kg (TOX15) and 20 µg/kg (TOX20) every other day. On the tenth injection respiratory mechanics (lung resistive and viscoelastic/inhomogeneous pressures, static elastance, and viscoelastic component of elastance) was measured. Lungs and liver were prepared for histology (morphometry and cellularity) and inflammatory mediators (KC and MIP-2) determination. All mechanical parameters and alveolar collapse were significantly higher in TOX5, 10, 15 and 20 than CTRL, but did not differ among them. Lung inflammatory cell content increased dose-dependently in all TOX groups in relation to CTRL, being TOX20 the largest. The production of KC was increased in lung and liver homogenates. MIP-2 increased in the liver of all TOX groups, but in lung homogenates it was significantly higher only in TOX20 group. All TOX mice livers showed steatosis, necrosis, inflammatory foci and a high degree of binucleated hepatocytes. In conclusion, sub-chronic exposure to MCLR damaged lung and liver in all doses, with a more important lung inflammation in TOX20 group.

Investigating the therapeutic effects of LASSBio-596 in an in vivo model of cylindrospermopsin-induced lung injury.

The cyanotoxin cylindrospermopsin (CYN) has lately been reported with a notorious toxicity to mammals. LASSBio-596 is a compound with anti-inflammatory actions. We aimed at evaluating the therapeutic effects of LASSBio-596 in a model of CYN-induced lung injury. Protocol #1: BALB/c mice received intratracheally (i.t.) 50-µL of saline or semi-purified extract of CYN (70 µg/kg). 18 h later, animals that received saline were gavaged with saline (SALSAL) or 50 mg/kg of LASSBio-596 (SALLAS), and mice that received CYN were gavaged with either saline (TOXSAL) or 50 mg/kg of LASSBio-596 (TOXLAS). Pulmonary mechanics was measured 6 h after gavage. Lungs were prepared for histology and inflammatory mediators determination. Protocol #2: Mice received 50-µL of CYN (70 µg/kg, i.t.) and 18 h later were gavaged with saline (NOT TREATED), or 50 mg/kg of LASSBio-596 (TREATED). Survival rates and pulmonary mechanics of the survivors were assessed. CYN exposure increased mechanical components, alveolar collapse, PMN cells and fiber deposition in the lungs, as well as the production of IL-1ß, IL-6 and KC in Protocol #1. LASSBio-596 attenuated those changes. TREATED mice in Protocol #2 presented significantly higher survival rates and tended to improve lung mechanics. Briefly, LASSBio-596 showed positive effects in mice exposed to CYN.