Compromised Lung Function Research Articles

Pharmaceutical targeting of succinate dehydrogenase in fibroblasts controls bleomycin-induced lung fibrosis

Idiopathic pulmonary fibrosis (IPF) is characterized by excessive deposition of extracellular matrix in the lung with fibroblast-to-myofibroblast transition, leading to chronically compromising lung function and death. However, very little is known about the metabolic alterations of fibroblasts in IPF, and there is still a lack of pharmaceutical agents to target the metabolic dysregulation. Here we show a glycolysis upregulation and fatty acid oxidation (FAO) downregulation in fibroblasts from fibrotic lung, and perturbation of glycolysis and FAO affects fibroblasts transdifferentiation. In addition, there is a significant accumulation of succinate both in fibrotic lung tissues and myofibroblasts, where succinate dehydrogenase (SDH) operates in reverse by reducing fumarate to succinate. Then succinate contributes to glycolysis upregulation and FAO downregulation by stabilizing HIF-1α, which promotes the development of lung fibrosis. In addition, we identify a near-infrared small molecule dye, IR-780, as a targeting agent which stimulates mild inhibition of succinate dehydrogenase subunit A (SDHA) in fibroblasts, and which inhibits TGF-β1 induced SDH and succinate elevation, then to prevent fibrosis formation and respiratory dysfunction. Further, enhanced cell retention of IR-780 is shown to promote severe inhibition of SDHA in myofibroblasts, which may contribute to excessive ROS generation and selectively induces myofibroblasts to apoptosis, and then therapeutically improves established lung fibrosis in vivo. These findings indicate that targeting metabolic dysregulation has significant implications for therapies aimed at lung fibrosis and succinate dehydrogenase is an exciting new therapeutic target to treat IPF.

The Paradox of Happy Hypoxia in COVID 19

Ever since the human race has been exposed to the novel COVID 19 illness, newer and newer intriguing features of the COVID viral plethora are seen with each passing day. Many manifestations of the COVID 19 illness have been baffling and unexplainable to researchers currently. One such unusual presentation seen is ‘happy hypoxia’ or silent hypoxemia in a third of patients' total number. This review article is intending to put some light on the puzzling condition of happy hypoxia. We authors refer you through various theories postulated for happy hypoxia. It has definite clinical implications in the sense that it can be lifesaving if detected early and promptly in a COVID patient. We conclude that happy hypoxia or silent hypoxemia is a new entity and should be diagnosed with a high index of suspicion in COVID suspect patients in both young patients with no co morbidities and the elderly and diabetics. Diagnostic modalities like pulse oximeter should be widely used at hospitals and clinics and for self-monitoring by the patients at homes. Also, chest X-rays or HRCT imaging of the lungs is essential in the early stages to identify the early infective changes with compromised lung function and rule out this happy hypoxia. Also, further research is essential to find the exact ethologic of this subclinical though ominous prognostic entity.

Assessment of risk factors responsible for rapid deterioration of lung function over a period of one year in patients with chronic obstructive pulmonary disease

Compromised lung function is a common feature of COPD patients, but certain factors increase the rate of lung function decline in COPD patients. The objective of the current study was to investigate the effect of different clinically important factors responsible for rapid deterioration of lung function quantified as ≥ 60 ml decline in FEV1 over a period of one year. COPD patients recruited from the chest clinic of Penang hospital were followed-up for one year from August 2018 to August 2019. Rapid deterioration of lung function was defined as greater than 60 ml/year decline in force expiratory volume in one second. Among 367 included patients 73.84% were male, with mean age 65.26 (9.6) years and % predicted FEV1 51.07 (11.84). 30.27% patients showed mean decline of ≥ 60 ml in FEV1. The regression analysis showed that current smoking relative risk (RR) = 2.38 (1.78–3.07), p < 0.001); GOLD Stage III& IV RR = 1.43 (1.27–1.97), p < 0.001); mMRC score 3 to 4 RR = 2.03 (1.74–2.70), p < 0.01); SGRQ-C score ≥ 10 points difference RR = 2.01 (1.58–2.73), p < 0.01); SGRQ-C symptoms Score ≥ 10 points difference RR = 1.48 (1.23–2.29), p < 0.001); 6MWT < 350 m RR = 2.29 (1.87–3.34), p < 0.01); ≥ 3 exacerbation in study year RR = 2.28 (1.58–2.42, p < 0.001); 8 or more hospital admission days (RR = 3.62 (2.66–4.20), p < 0.001); Charlson comorbidity index ≥ 3 RR = 3.18 (2.23–3.76), p < 0.01) and emphysema RR = 1.31 (1.15–1.79), p < 0.01) were significant risk factors for the rapid deterioration of lung function (FEV1 decline ≥ 60 ml). Among different factors CCI score ≥ 3, abrupt decline in health status, exacerbation frequency ≥ 3, hospital admission days ≥ 8 and emphysema were reported as risk factors for rapid deterioration of lung function.

Non-intubated uniportal VATS right upper sleeve lobectomy in a patient with compromised lung function

Non-intubated uniportal VATS right upper sleeve lobectomy in a patient with compromised lung function

Effect of Dietary Nitrate Supplementation on Sleep in Chronic Obstructive Pulmonary Disease Patients.

PurposePoor sleep quality in chronic obstructive pulmonary disease (COPD) is a result of oxygen desaturation secondary to compromised lung function. Nitrate supplementation with dietary beetroot juice is known to elevate plasma nitrate and to increase the efficiency of oxygen utilization in non-COPD individuals; whether it is of therapeutic benefit for sleep quality in COPD has not been reported.Patients and MethodsIn a counterbalanced within-subjects design involving 15 COPD patients as subjects, the subjects consumed either beetroot juice containing nitrate (BJ; ∼6.2 mmol NO3–) or placebo (NO3– -depleted juice) immediately before a night of polysomnographic monitoring. Nitrate was measured in plasma collected immediately after waking.ResultsWhile BJ consumption had no effect on the amount of time spent in any sleep stages, wake-to-N2 transitions and direct wake-to-rapid eye movement sleep (REMS) transitions, hallmarks of disordered sleep, were less frequent on the BJ night than on the placebo night. In the last two hours of the BJ night, percent time in REMS increased and delta power during deep (N3) non-REMS decreased, relative to the placebo night. Collectively, the reduced frequency of atypical transitions and the normalization of non-REMS/REMS dynamics after BJ are indicative of an improvement of sleep quality. BJ also resulted in sustained elevation of peripheral oxygen saturation (SpO2), during episodes of wake after sleep onset. Plasma nitrate was elevated nearly tenfold on the morning after BJ relative to placebo.ConclusionBJ has a normalizing effect on disordered sleep in COPD, which may be related to improved oxygen delivery.Clinical Trial RegistrationThe activities of the Regional Committees for Medical and Health Research Ethics (REC) are founded on the Norwegian law on research ethics and medical research. This study was approved by NTNU/REK midt, Det medisinske fakultet, Postboks 8905, 7491 Trondheim (REK midt 2016/1360).

A proposed molecular mechanism for pathogenesis of severe RNA-viral pulmonary infections.

Background: Certain riboviruses can cause severe pulmonary complications leading to death in some infected patients. We propose that DNA damage induced-apoptosis accelerates viral release, triggered by depletion of host RNA binding proteins (RBPs) from nuclear RNA bound to replicating viral sequences. Methods: Information theory-based analysis of interactions between RBPs and individual sequences in the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), Influenza A (H3N2), HIV-1, and Dengue genomes identifies strong RBP binding sites in these viral genomes. Replication and expression of viral sequences is expected to increasingly sequester RBPs - SRSF1 and RNPS1. Ordinarily, RBPs bound to nascent host transcripts prevents their annealing to complementary DNA. Their depletion induces destabilizing R-loops. Chromosomal breakage occurs when an excess of unresolved R-loops collide with incoming replication forks, overwhelming the DNA repair machinery. We estimated stoichiometry of inhibition of RBPs in host nuclear RNA by counting competing binding sites in replicating viral genomes and host RNA. Results: Host RBP binding sites are frequent and conserved among different strains of RNA viral genomes. Similar binding motifs of SRSF1 and RNPS1 explain why DNA damage resulting from SRSF1 depletion is complemented by expression of RNPS1. Clustering of strong RBP binding sites coincides with the distribution of RNA-DNA hybridization sites across the genome. SARS-CoV-2 replication is estimated to require 32.5-41.8 hours to effectively compete for binding of an equal proportion of SRSF1 binding sites in host encoded nuclear RNAs. Significant changes in expression of transcripts encoding DNA repair and apoptotic proteins were found in an analysis of influenza A and Dengue-infected cells in some individuals. Conclusions: R-loop-induced apoptosis indirectly resulting from viral replication could release significant quantities of membrane-associated virions into neighboring alveoli. These could infect adjacent pneumocytes and other tissues, rapidly compromising lung function, causing multiorgan system failure and other described symptoms.

Serum Nickel Levels Compromise the Oxidative Status and Lung Functions in Ceramic Workers

Nickel, in the form of various alloys and compounds, has been in widespread commercial use for over 100 years. Several million workers worldwide are exposed to airborne fumes, dust, and mist containing nickel and its compounds. Further, exposures by inhalation, ingestion, or skin contact occur in nickel-producing industries, like mining, milling, melting, and refining, and in nickel-using industries, like electroplating, welding, and grinding. Insoluble nickel is the predominant exposure in nickel-producing industries, whereas soluble nickel is the predominant exposure in nickel-using industries like the ceramics industry. This study was designed to extrapolate the levels of serum nickel, antioxidant compounds, and stress markers and correlate them with lung function status in craft workers in the ceramics industry. The study included 50 fiber craft workers from the ceramics industry who met the inclusion criteria. The control group consisted of subjects from the general population with no disease. Blood samples from the workers were collected by a phlebotomist. The levels of nickel and biological antioxidants, i.e. serum glutathione (GSH) and stress marker malondialdehye (MDA), were determined. Estimation of oxidants and haptoglobin (Hp) levels were assessed. The level of nickel was measured by atomic absorption spectrophotometry. A spirometer was used to measure lung functions. The calculated levels of these parameters were compared with those in the control subjects. An overall increase in nickel and MDA levels and a decrease in GSH level were observed. When these workers were classified into groups, it was observed that prolonged employment in the ceramics industry was associated with an increased nickel concentration in the serum, which in turn increased oxidative stress biomarkers and thus decreased the antioxidant levels to the lower limit. The decrease in GSH level compromises lung function. Our findings of an increase the Hp level is noteworthy, as it increased by 89% in the group with over 10 years of service in the industry compared with the group working for less than 5 years. Prolonged exposure of nickel increases the oxidative stress, in terms of increased MDA level and decreased GSH level. These findings can compromise the lung function and increase the Hp level.

Inhaled Antifungal Agents for the Treatment and Prophylaxis of Pulmonary Mycoses.

Pulmonary mycoses are associated with high morbidity and mortality. The current standard treatment by systemic administration is limited by inadequate local bioavailability and systemic toxic effects. Aerosolisation of antifungals is an attractive approach to overcome these problems, but no inhaled antifungal formulation is currently available for the treatment of pulmonary mycoses. Hence, the development of respirable antifungals formulations is of interest and in high demand. In this review, the recent advances in the development of antifungal formulations for pulmonary delivery are discussed, including both nebulised and dry powder formulations. Although the clinical practices of nebulised parenteral amphotericin B and voriconazole formulations (off-label use) are reported to show promising therapeutic effects with few adverse effects, there is no consensus about the dosage regimen (e.g. the dose, frequency, and whether they are used as single or combination therapy). To maximise the benefits of nebulised antifungal therapy, it is important to establish standardised protocol that clearly defines the dose and specifies the device and the administration conditions. Dry powder formulations of antifungal agents such as itraconazole and voriconazole with favourable physicochemical and aerosol properties are developed using various powder engineering technologies, but it is important to consider their suitability for use in patients with compromised lung functions. In addition, more biological studies on the therapeutic efficacy and pharmacokinetic profile are needed to demonstrate their clinical potential.

Fucoidan and Lung Function: Value in Viral Infection.

Compromised lung function is a feature of both infection driven and non-infective pathologies. Viral infections—including the current pandemic strain SARS-CoV-2—that affect lung function can cause both acute and long-term chronic damage. SARS-CoV-2 infection suppresses innate immunity and promotes an inflammatory response. Targeting these aspects of SARS-CoV-2 is important as the pandemic affects greater proportions of the population. In clinical and animal studies, fucoidans have been shown to increase innate immunity and decrease inflammation. In addition, dietary fucoidan has been shown to attenuate pulmonary damage in a model of acute viral infection. Direct inhibition of SARS-CoV-2 in vitro has been described, but is not universal. This short review summarizes the current research on fucoidan with regard to viral lung infections and lung damage.

A proposed molecular mechanism for pathogenesis of severe RNA-viral pulmonary infections

Background: Certain riboviruses can cause severe pulmonary complications leading to death in some infected patients. We propose that DNA damage induced-apoptosis accelerates viral release, triggered by depletion of host RNA binding proteins (RBPs) from nuclear RNA bound to replicating viral sequences. Methods: Information theory-based analysis of interactions between RBPs and individual sequences in the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), Influenza A (H3N2), HIV-1, and Dengue genomes identifies strong RBP binding sites in these viral genomes. Replication and expression of viral sequences is expected to increasingly sequester RBPs - SRSF1 and RNPS1. Ordinarily, RBPs bound to nascent host transcripts prevents their annealing to complementary DNA. Their depletion induces destabilizing R-loops. Chromosomal breakage occurs when an excess of unresolved R-loops collide with incoming replication forks, overwhelming the DNA repair machinery. We estimated stoichiometry of inhibition of RBPs in host nuclear RNA by counting competing binding sites in replicating viral genomes and host RNA. Results: Host RBP binding sites are frequent and conserved among different strains of RNA viral genomes. Similar binding motifs of SRSF1 and RNPS1 explain why DNA damage resulting from SRSF1 depletion is complemented by expression of RNPS1. Clustering of strong RBP binding sites coincides with the distribution of RNA-DNA hybridization sites across the genome. SARS-CoV-2 replication is estimated to require 32.5-41.8 hours to effectively compete for binding of an equal proportion of SRSF1 binding sites in host encoded nuclear RNAs. Significant changes in expression of transcripts encoding DNA repair and apoptotic proteins were found in an analysis of influenza A and Dengue-infected cells in some individuals. Conclusions: R-loop-induced apoptosis indirectly resulting from viral replication could release significant quantities of membrane-associated virions into neighboring alveoli. These could infect adjacent pneumocytes and other tissues, rapidly compromising lung function, causing multiorgan system failure and other described symptoms.

Effects of bronchial blockers on gas exchange in infants with one-lung ventilation: a single-institutional experience of 22 cases.

BackgroundOne-lung ventilation (OLV) in infants is a commonly used airway technique during thoracic surgery. Current research has primarily focused on the operation of the airways and the occurrence of complications. However, there has been minimal data on the pulmonary gas exchange in infants before and after OLV. This study aimed to assess the efficacy of bronchial blockers (BBs) on the pulmonary gas exchange in infants with OLV.MethodsA total of 22 infants requiring OLV from January 2017 to August 2019 were included in this study. OLV was achieved by placing BBs outside the endotracheal tube, and all surgeries were performed by the same experienced anesthesiologist. Numerous clinical features, including the oxygenation index (OI), alveolar-arterial oxygen tension gradient (PA-aO2), pulmonary dynamic compliance (Cdyn), OLV time, pulmonary collapse time, degree of pulmonary collapse at the operative side, operative time, and immediate hemodynamic indexes before and after intubation were assessed. Data from the arterial blood gases and the ventilator’s parameters were obtained at three time points: 15 minutes before OLV (pre-OLV), 15 minutes after the initiation of OLV (during OLV), and 15 minutes after the termination of OLV (post-OLV).ResultsFor all patients, the pulmonary gas exchange during OLV was significantly different from both pre-OLV and post-OLV. However, no significant changes of pulmonary function were observed before and after OLV. Extended OLV time was associated with decreased OI and Cdyn, and increased PA-aO2 gradient (P<0.001). In addition, no significant changes of hemodynamic indexes before and after intubation were detected. The degree of lung collapse on the operational side during OLV was optimal.ConclusionsIn this study, the efficacy of BBs on the pulmonary gas exchange in infants with OLV was assessed. The results suggested that although each parameter of pulmonary function pre-OLV were similar to those of post-OLV, an extended period of OLV may lead to compromised lung function.

Adenosine and ATP\u03b3S protect against bacterial pneumonia-induced acute lung injury

Lipopolysaccharide (LPS), a component of the outer membrane of gram-negative bacteria, disrupts the alveolar-capillary barrier, triggering pulmonary vascular leak thus inducing acute lung injury (ALI). Extracellular purines, adenosine and ATP, protected against ALI induced by purified LPS. In this study, we investigated whether these purines can impact vascular injury in more clinically-relevant E.coli (non-sterile LPS) murine ALI model. Mice were inoculated with live E. coli intratracheally (i.t.) with or without adenosine or a non-hydrolyzable ATP analog, adenosine 5′-(γ-thio)-triphosphate (ATPγS) added intravenously (i.v.). After 24 h of E. coli treatment, we found that injections of either adenosine or ATPγS 15 min prior or adenosine 3 h after E.coli insult significantly attenuated the E.coli-mediated increase in inflammatory responses. Furthermore, adenosine prevented weight loss, tachycardia, and compromised lung function in E. coli-exposed mice. Accordingly, treatment with adenosine or ATPγS increased oxygen saturation and reduced histopathological signs of lung injury in mice exposed to E. coli. Lastly, lung-targeting gene delivery of adenosine or ATPγS downstream effector, myosin phosphatase, significantly attenuated the E. coli-induced compromise of lung function. Collectively, our study has demonstrated that adenosine or ATPγS mitigates E. coli-induced ALI in mice and may be useful as an adjuvant therapy in future pre-clinical studies.

Allogeneic administration of human umbilical cord-derived mesenchymal stem/stromal cells for bronchopulmonary dysplasia: preliminary outcomes in four Vietnamese infants

BackgroundBronchopulmonary dysplasia (BPD) is a severe condition in premature infants that compromises lung function and necessitates oxygen support. Despite major improvements in perinatal care minimizing the devastating effects, BPD remains the most frequent complication of extreme preterm birth. Our study reports the safety of the allogeneic administration of umbilical cord-derived mesenchymal stem/stromal cells (allo-UC-MSCs) and the progression of lung development in four infants with established BPD.MethodsUC tissue was collected from a healthy donor, followed by propagation at the Stem Cell Core Facility at Vinmec Research Institute of Stem Cell and Gene Technology. UC-MSC culture was conducted under xeno- and serum-free conditions. Four patients with established BPD were enrolled in this study between May 25, 2018, and December 31, 2018. All four patients received two intravenous doses of allo-UC-MSCs (1 million cells/kg patient body weight (PBW) per dose) with an intervening interval of 7 days. Safety and patient conditions were evaluated during hospitalization and at 7 days and 1, 6 and 12 months postdischarge.ResultsNo intervention-associated severe adverse events or prespecified adverse events were observed in the four patients throughout the study period. At the time of this report, all patients had recovered from BPD and were weaned off of oxygen support. Chest X-rays and CT scans confirmed the progressive reductions in fibrosis.ConclusionsAllo-UC-MSC administration is safe in preterm infants with established BPD.Trial registration This preliminary study was approved by the Vinmec International Hospital Ethics Board (approval number: 88/2019/QĐ-VMEC; retrospectively registered March 12, 2019).

Adherence to Dietary Recommendations, Nutrient Intake Adequacy and Diet Quality among Pediatric Cystic Fibrosis Patients: Results from the GreeCF Study.

Nutrition is an important component of cystic fibrosis (CF) therapy, with a high-fat diet being the cornerstone of treatment. However, adherence to the dietary recommendations for CF appears suboptimal and burdensome for most children and adolescents with CF, leading to malnutrition, inadequate growth, compromised lung function and increased risk for respiratory infections. A cross-sectional approach was deployed to examine the degree of adherence to the nutrition recommendations and diet quality among children with CF. A total of 76 children were recruited from Aghia Sophia’s Children Hospital, in Athens, Greece. In their majority, participants attained their ideal body weight, met the recommendations for energy and fat intake, exceeding the goal for saturated fatty acids consumption. Carbohydrate and fiber intake were suboptimal and most participants exhibited low or mediocre adherence to the Mediterranean diet prototype. It appears that despite the optimal adherence to the energy and fat recommendations, there is still room for improvement concerning diet quality and fiber intake.

The Potential Role and Regulatory Mechanisms of MUC5AC in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality globally. Studies show that airway mucus hypersecretion strongly compromises lung function, leading to frequent hospitalization and mortality, highlighting an urgent need for effective COPD treatments. MUC5AC is known to contribute to severe muco-obstructive lung diseases, worsening COPD pathogenesis. Various pathways are implicated in the aberrant MUC5AC production and secretion MUC5AC. These include signaling pathways associated with mucus-secreting cell differentiation [nuclear factor-κB (NF-κB)and IL-13-STAT6- SAM pointed domain containing E26 transformation-specific transcription factor (SPDEF), as well as epithelial sodium channel (ENaC) and cystic fibrosis transmembrane conductance regulator (CFTR)], and signaling pathways related to mucus transport and excretion-ciliary beat frequency (CBF). Various inhibitors of mucus hypersecretion are in clinical use but have had limited benefits against COPD. Thus, novel therapies targeting airway mucus hypersecretion should be developed for effective management of muco-obstructive lung disease. Here, we systematically review the mechanisms and pathogenesis of airway mucus hypersecretion, with emphasis on multi-target and multi-link intervention strategies for the elucidation of novel inhibitors of airway mucus hypersecretion.

A proposed molecular mechanism for pathogenesis of severe RNA-viral pulmonary infections.

Background: Certain riboviruses can cause severe pulmonary complications leading to death in some infected patients. We propose that DNA damage induced-apoptosis accelerates viral release, triggered by depletion of host RNA binding proteins (RBPs) from nuclear RNA bound to replicating viral sequences. Methods: Information theory-based analysis of interactions between RBPs and individual sequences in the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), Influenza A (H3N1), HIV-1, and Dengue genomes identifies strong RBP binding sites in these viral genomes. Replication and expression of viral sequences is expected to increasingly sequester RBPs - SRSF1 and RNPS1. Ordinarily, RBPs bound to nascent host transcripts prevents their annealing to complementary DNA. Their depletion induces destabilizing R-loops. Chromosomal breakage occurs when an excess of unresolved R-loops collide with incoming replication forks, overwhelming the DNA repair machinery. We estimated stoichiometry of inhibition of RBPs in host nuclear RNA by counting competing binding sites in replicating viral genomes and host RNA. Results: Host RBP binding sites are frequent and conserved among different strains of RNA viral genomes. Similar binding motifs of SRSF1 and RNPS1 explain why DNA damage resulting from SRSF1 depletion is complemented by expression of RNPS1. Clustering of strong RBP binding sites coincides with the distribution of RNA-DNA hybridization sites across the genome. SARS-CoV-2 replication is estimated to require 32.5-41.8 hours to effectively compete for binding of an equal proportion of SRSF1 binding sites in host encoded nuclear RNAs. Significant changes in expression of transcripts encoding DNA repair and apoptotic proteins were found in an analysis of influenza A and Dengue-infected cells in some individuals. Conclusions: R-loop-induced apoptosis indirectly resulting from viral replication could release significant quantities of membrane-associated virions into neighboring alveoli. These could infect adjacent pneumocytes and other tissues, rapidly compromising lung function, causing multiorgan system failure and other described symptoms.

Surgical treatment of bilateral vanishing lung syndrome: a case report

BackgroundVolume reduction surgery is a routine treatment method for lung emphysema in chronic obstructive pulmonary disease (COPD) patients. The formation of giant bullous emphysema is an indication for surgical bullectomy. Bilateral giant bullae severely compromise lung function and complicate surgical treatment.Case presentationWe present the algorithm for surgical treatment and correction of complications in a 38-year-old male with bilateral giant bullae (vanishing lung syndrome), severe COPD. Primarily the patient was admitted with a mild cough, mucopurulent sputum and dyspnea. A CT scan revealed bilateral giant bullae, displacing up to 50% of lung volume. A two-stage surgical bullectomy was planned, yet postoperative complications due to secondary bullae rupture prompted urgent revision with contralateral bullae resection. After complete bullectomy, severely reduced lung volume was successfully managed throughout a long postoperative rehabilitation period. At 5 year follow-up, spirometry indicators and radiological examination show significantly improved and stable lung function.ConclusionThis clinical case demonstrates the technical difficulties and possible complications of extended bilateral lung resections in patients with severe vanishing lung syndrome. Single-stage treatment of bilateral giant bullous emphysema is recommended to minimize postoperative complications and reduce risk of bullae rupture. Positive long-term outcome outweighs possible complications of surgical treatment.

The extracellular matrix and mechanotransduction in pulmonary fibrosis.

Pulmonary fibrosis is characterised by excessive scarring in the lung which leads to compromised lung function, serious breathing problems and in some diseases, death. It includes several lung disorders with idiopathic pulmonary fibrosis (IPF) the most common and most severe. Pulmonary fibrosis is considered to be perpetuated by aberrant wound healing which leads to fibroblast accumulation, differentiation and activation, and deposition of excessive amounts of extracellular matrix (ECM) components, in particular, collagen. Recent studies have identified the importance of changes in the composition and structure of lung ECM during the development of pulmonary fibrosis and the interaction between ECM and lung cells. There is strong evidence that increased matrix stiffness induces changes in cell function including proliferation, migration, differentiation and activation. Understanding how changes in the ECM microenvironment influence cell behaviour during fibrogenesis, and the mechanisms regulating these changes, will provide insight for developing new treatments.

Comparison of reduced-toxicity conditioning protocols using fludarabine, melphalan combined with thiotepa or carmustine in allogeneic hematopoietic cell transplantation.

The age of patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) has increased during the last decades, mainly due to improved reduced-intensity/toxicity conditioning protocols. A reduced-intensity conditioning based on fludarabin, carmustin/BCNU and melphalan (FBM) has been previously developed at our institution. Since we observed detrimental effects in individual patients with compromised lung function, efforts have been made in order to replace BCNU by thiotepa (FTM) to reduce toxicity. In this study, we retrospectively analyzed the outcome, GvHD incidence, lung function and organ toxicity of patients with a median age of 62 years (range 21–79) transplanted for malignant disease (96.7%, 62.3% in intermediate/advanced disease stage) at our institution after conditioning with FBM (n = 136) or FTM (n = 105) between 2013 and 2017. Median follow-up was 868 days (range 0–2615). In multivariate analysis for overall survival, no difference was detected between both conditioning protocols in the presence of impaired lung function, age, lower performance, and liver disease previous allo-HCT. In the subgroup analysis, FTM was not inferior to FBM in patients with pulmonary disease prior allo-HCT, lymphoid malignancies, and higher comorbidity index. In conclusion, the reduced-intensity FBM and FTM conditioning protocols show adequate antineoplastic efficacy and are suitable for patients with impaired lung function.

Use of Procalcitonin for Identification of Cobacterial Pneumonia in Pediatric Patients.

To evaluate the utility of procalcitonin (PCT) in identifying cobacterial pneumonia in pediatric patients with known viral respiratory infection. A retrospective cohort study was conducted in a stand-alone children's hospital during 2 time periods (period 1: October 1, 2014, to March 31, 2015; period 2: October 1, 2015, to March 31, 2016). Patients admitted with any upper respiratory tract infection were included. Exclusion criteria included any condition compromising lung function, age <30 days or >18 years, or lack of PCT (period 2). PCT values of <0.5 ng/mL were considered normal, whereas values of >1.5 ng/mL were used to identify cobacterial pneumonia. Receiver-operator characteristic curves were used with multiple logistic regression to evaluate patient variables. Of the 374 pediatric patients evaluated, 64% were classified as having viral pneumonia and 23% as having cobacterial pneumonia across both study time periods. Non-significant predictors of cobacterial pneumonia included temperature (p = 0.0795, p = 0.1466), WBC count (p = 0.8774, p = 0.6675), and C-reactive protein (p = 0.7115, p = 0.3835). Median initial PCT for patients with viral pneumonia was 0.14 ng/mL compared with 1.41 ng/mL in patients with cobacterial pneumonia; median second PCTs were 0.26 ng/mL (viral pneumonia) and 4.55 ng/mL (cobacterial pneumonia). Patients with an elevated PCT had 17.5 times (95% CI, 5.2, 59.1) greater odds of having a cobacterial pneumonia. PCT was found to be strongly associated with cobacterial pneumonia with an underlying viral etiology. Temperature, WBC, and C-reactive protein failed to be significant predictors in differentiating between viral and cobacterial pneumonia.