Alveolar Level Research Articles

Surfactant Therapy for Bronchiolitis in Critically Ill Infants

Daphne Stannard, the contributing editor for the Cochrane Review Summary, is the chief nurse researcher and director of the Institute for Nursing Excellence at UCSF Medical Center, San Francisco, California. She is also the director of the UCSF JBI Centre.For questions related to this article, contact Daphne Stannard at daphne.stannard@ucsfmedctr.org.How effective is exogenous surfactant administration (ie, intratracheal administration of surfactant of any type, at any dose, and at any time after start of mechanical ventilation) compared with placebo, no intervention, or standard care in reducing mortality and duration of ventilation in infants and children with bronchiolitis requiring mechanical ventilation?Pulmonary surfactant is an endogenous phospholipid compound that is synthesized and secreted by type II alveolar cells. Surfactant greatly reduces surface tension within the alveoli, helping to prevent alveolar collapse. Additionally, low surface tension at the alveolar level increases overall compliance of the lung and reduces the work of breathing. Surfactant is formed late in fetal life, and babies born without adequate amounts often have significant morbidity and mortality.1 Two types of exogenous surfactants are available for clinical use: animal (porcine and bovine) and synthetic. Use of exogenous surfactants in preterm babies with respiratory distress syndrome/hyaline membrane disease has been extensively studied and is now considered the standard treatment for this condition.Surfactant abnormalities have been observed in severe cases of bronchiolitis or inflammation of the small airways in the lung.2 Although bronchiolitis is a frequent cause of respiratory failure in infants and children, there is no effective therapy available except for supportive care (which includes adequate fluid intake, antipyretics, and oxygen supplementation as needed). While many therapeutic interventions other than supportive care have been used to treat bronchiolitis, including exogenous surfactant administration, their effectiveness is not well documented.This summary is based on a Cochrane systematic review containing 3 small randomized controlled trials, which included a total of 79 participants. Primary outcomes included mortality, duration of mechanical ventilation in hours, and adverse effects. For the purposes of this review, adverse effects included desaturation, change in heart rate and/or blood pressure, bronchospasm, and other complications such as pneumothorax. Secondary outcomes included the following:Two of the studies were from Italy, and one was from the United Kingdom (UK). One of the Italian studies was a multicenter trial that included 6 centers. The age of the included participants ranged from 1 week to 2.5 years in the Italian studies and a median age of 2 months in the surfactant group and 1.4 months in the control group in the UK study. No major difference in distribution of the sexes was apparent among the studies, with 40 males and 39 females.Most participants had respiratory syncytial virus–induced respiratory failure except for in 1 Italian study, where the viral origin was known only in 20% of the cases (n=20) and these cases were positive for respiratory syncytial virus. This same study enrolled patients when they were receiving mechanical ventilation for 24 hours without significant clinical improvement, and porcine surfactant was used 50 mg/kg in 2 to 3 doses. The multicenter Italian study included participants who were receiving mechanical ventilation for at least 12 hours without significant improvement, and porcine surfactant was used 50 mg/kg in 2 aliquots over 5 minutes. The UK study enrolled participants who had been receiving mechanical ventilation for less than 24 hours, and bovine surfactant was administered in 2 doses (100 mg/kg) 24 hours apart. The exogenous surfactant was administered through an endotracheal tube in all studies. The Italian studies used no placebo in the control arms, and the UK study used an air placebo.Participants with uncorrected congenital heart disease and neuromuscular diseases were excluded in 2 studies. The Italian multicenter study also excluded children with chronic lung disease, whereas the UK study did not exclude children with chronic lung disease or a history of prematurity. The risk of bias was unclear in some of the included studies, but none of the included studies had a high risk of bias.Dichotomous outcomes were analyzed by calculating the risk ratio and risk difference. Continuous outcomes were analyzed as mean differences. The overall results were expressed with 95% confidence intervals (CIs). Both clinical and methodological heterogeneity was assessed before pooling by using the χ2 test and the I2 statistic. A fixed-effect model was used and statistical analyses were performed by using RevMan 2011 (Cochrane Software).The available evidence is insufficient to establish the effectiveness of surfactant therapy for bronchiolitis in critically ill infants who require mechanical ventilation. Larger trials with adequate power to evaluate the effectiveness of exogenous surfactant therapy for infants with bronchiolitis who require intensive care are needed.3

Effect of Aerosolized Colistin as Adjunctive Treatment on the Outcomes of Microbiologically Documented Ventilator-Associated Pneumonia Caused by Colistin-Only Susceptible Gram-Negative Bacteria

The increasing frequency of ventilator-associated pneumonia (VAP) caused by colistin-only susceptible (COS) gram-negative bacteria (GNB) is of great concern. Adjunctive aerosolized (AS) colistin can reportedly increase alveolar levels of the drug without increasing systemic toxicity. Good clinical results have been obtained in patients with cystic fibrosis, but conflicting data have been reported in patients with VAP. We conducted a retrospective, 1:1 matched case-control study to evaluate the efficacy and safety of AS plus IV colistin vs IV colistin alone in 208 patients in the ICU with VAP caused by COS Acinetobacter baumannii, Pseudomonas aeruginosa, or Klebsiella pneumoniae. Compared with the IV colistin cohort, the AS-IV colistin cohort had a higher clinical cure rate (69.2% vs 54.8%, P = .03) and required fewer days of mechanical ventilation after VAP onset (8 days vs 12 days, P = .001). In the 166 patients with posttreatment cultures, eradication of the causative organism was also more common in the AS-IV colistin group (63.4% vs 50%, P = .08). No between-cohort differences were observed in all-cause ICU mortality, length of ICU stay after VAP onset, or rates of acute kidney injury (AKI) during colistin therapy. Independent predictors of clinical cure were trauma-related ICU admission (P = .01) and combined AS-IV colistin therapy (P = .009). Higher mean Simplified Acute Physiology Score II (P = .002) and Sequential Organ Failure Assessment (P = .05) scores, septic shock (P < .001), and AKI onset during colistin treatment (P = .04) were independently associated with clinical failure. Our results suggest that AS colistin might be a beneficial adjunct to IV colistin in the management of VAP caused by COS GNB.

Preliminary study on measuring interdental papilla height and thickness of the maxillary anterior teeth based on cone-beam computed tomography

To investigate the features of the fill of interdental spaces by gingival papillae and the associated factors. Fifteen volunteers with healthy gingiva were involved in this study. The height and thickness on the alveolar crest level of 62 maxillary anterior papilla were measured radiographically with cone-beam computed tomography (CBCT) scans. A standardized periodontal probe with Williams markings was used for measurements of the papilla width on the alveolar crest level. When the papilla was complete fill interdentally, the mean height of papillary tissue on the alveolar crest level (equal to contact point-bone crest) was (3.67 ± 0.51) mm. The mean thickness of papilla on the alveolar crest level was (8.38 ± 0.75) mm. The papilla height had a positive correlation with papilla thickness (r = 0.433, P < 0.001). The cone-beam computed tomography can be used for clear visualization of the papilla profile and the measurements of papilla height and thickness. Thicker and wider tissue was associated with an increased likelihood of having a complete papilla fill.

Is Time the Missing Component in Protective Ventilation Strategies?*

Is Time the Missing Component in Protective Ventilation Strategies?*

Syndecan-2 Exerts Antifibrotic Effects by Promoting Caveolin-1–mediated Transforming Growth Factor-β Receptor I Internalization and Inhibiting Transforming Growth Factor-β1 Signaling

Alveolar transforming growth factor (TGF)-β1 signaling and expression of TGF-β1 target genes are increased in patients with idiopathic pulmonary fibrosis (IPF) and in animal models of pulmonary fibrosis. Internalization and degradation of TGF-β receptor TβRI inhibits TGF-β signaling and could attenuate development of experimental lung fibrosis. To demonstrate that after experimental lung injury, human syndecan-2 confers antifibrotic effects by inhibiting TGF-β1 signaling in alveolar epithelial cells. Microarray assays were performed to identify genes differentially expressed in alveolar macrophages of patients with IPF versus control subjects. Transgenic mice that constitutively overexpress human syndecan-2 in macrophages were developed to test the antifibrotic properties of syndecan-2. In vitro assays were performed to determine syndecan-2-dependent changes in epithelial cell TGF-β1 signaling, TGF-β1, and TβRI internalization and apoptosis. Wild-type mice were treated with recombinant human syndecan-2 during the fibrotic phase of bleomycin-induced lung injury. We observed significant increases in alveolar macrophage syndecan-2 levels in patients with IPF. Macrophage-specific overexpression of human syndecan-2 in transgenic mice conferred antifibrotic effects after lung injury by inhibiting TGF-β1 signaling and downstream expression of TGF-β1 target genes, reducing extracellular matrix production and alveolar epithelial cell apoptosis. In vitro, syndecan-2 promoted caveolin-1-dependent internalization of TGF-β1 and TβRI in alveolar epithelial cells, which inhibited TGF-β1 signaling and epithelial cell apoptosis. Therapeutic administration of human syndecan-2 abrogated lung fibrosis in mice. Alveolar macrophage syndecan-2 exerts antifibrotic effects by promoting caveolin-1-dependent TGF-β1 and TβRI internalization and inhibiting TGF-β1 signaling in alveolar epithelial cells. Hence, molecules that facilitate TβRI degradation via endocytosis represent potential therapies for pulmonary fibrosis.

Guidance on the use of respiratory and facial protection equipment

Infectious micro-organisms may be transmitted by a variety of routes, and some may be spread by more than one route. Respiratory and facial protection is required for those organisms that are usually transmitted via the droplet/airborne route, or when airborne particles have been artificially created, such as during ‘aerosol-generating procedures’. A range of personal protective equipment that provides different degrees of facial and respiratory protection is available. It is apparent from the recent experiences with severe acute respiratory syndrome and pandemic (H1N1) 2009 influenza that healthcare workers may have difficulty in choosing the correct type of facial and respiratory protection in any given clinical situation. To address this issue, the Scientific Development Committee of the Healthcare Infection Society established a short-life working group to develop guidance. The guidance is based upon a review of the literature, which is published separately, and expert consensus.

Alveolar epithelial cells: Master regulators of lung homeostasis

The lung interfaces with the environment across a continuous epithelium composed of various cell types along the proximal and distal airways. At the alveolar structure level, the epithelium, which is composed of type I and type II alveolar epithelial cells, represents a critical component of lung homeostasis. Indeed, its fundamental role is to provide an extensive surface for gas exchange. Additional functions that act to preserve the capacity for such unique gas transfer have been progressively identified. The alveolar epithelium represents a physical barrier that protects from environmental insults by segregating inhaled foreign agents and regulating water and ions transport, thereby contributing to the maintenance of alveolar surface fluid balance. The homeostatic role of alveolar epithelium relies on the regulated/controlled production of the pulmonary surfactant, which is not only a key determinant of alveolar mechanical stability but also a complex structure that participates in the cross-talk between local cells and the lung immune and inflammatory response. In regard to these critical functions, a major point is the maintenance of alveolar surface integrity, which relies on the renewal capacity of type II alveolar epithelial cells, and the contribution of progenitor populations within the lung.

Myofibroblast expression in airways and alveoli is affected by smoking and COPD

BackgroundChronic obstructive pulmonary disease (COPD) is characterized by structural changes in alveoli and airways. Our aim was to analyse the numbers of alpha-smooth muscle actin (α-SMA) positive cells, as a marker of myofibroblasts, in different lung compartments in non-smokers and smokers with normal lung function or COPD.Methodsα-SMA, tenascin-C (Tn-C) and EDA-fibronectin in alveolar level and airways were assayed by immunohistochemistry and quantified by image analysis. Immunohistochemical findings were correlated with clinical data. α-SMA protein was also analysed by Western blotting from fibroblastic cells cultured from peripheral lung of non-smokers, smokers without COPD and smokers with COPD.ResultsIn many cases, the endings of the detached alveolar walls were widened, the structures of which were named as widened alveolar tips. Widened alveolar tips contained α-SMA positive cells, which were obviously myofibroblasts. There were less alveolar tips containing positive cells for α-SMA in alveoli and α-SMA positive cells in bronchioles in smokers and in COPD compared to non-smokers. The quantity of α-SMA positive cells was increased in bronchi in COPD. Tn-C was elevated in bronchi in COPD and smokers’ lung. The α-SMA protein level was 1.43-fold higher in stromal cells cultured from non-smokers than in those of smokers.ConclusionsMyofibroblasts are localized variably in normal and diseased lung. This indicates that they have roles in both regeneration of lung and pathogenesis of COPD. The widened alveolar tips, these newly characterized histological structures, seemed to be the source of myofibroblasts at the alveolar level.

Influence of presence or absence of keratinized mucosa on the alveolar bony crest level as it relates to different buccal marginal bone thicknesses. An experimental study in dogs

To investigate the influence of the presence or absence of keratinized mucosa on the alveolar bony crest level as it relates to different buccal marginal bone thicknesses. In six beagle dogs, the mandibular premolars and first molars were extracted bilaterally. In the right side of the mandible (test), flaps were elevated, and the buccal as well as part of the lingual masticatory mucosa was removed. The flap was released coronally to allow a primary wound closure. In the left side, the wounds were left unsutured with the keratinized mucosa remaining (control). After 3months of healing, a complete absence of keratinized mucosa was found at the test sites. Two recipient sites were prepared at each side of the mandible, one in the premolar and one in the molar region. A buccal bony ridge width of approximately 1 and 2mm was obtained at the premolar and molar region, respectively. Implants were installed with the shoulder flush with the buccal alveolar bony crest, and abutments were connected to allow a nonsubmerged healing. At least 2mm of keratinized mucosa was surrounding the control sites, while at the test sites, the implants were bordered by alveolar mucosa. After 3months, the animals were euthanized and ground sections obtained. A higher vertical bony crest resorption was observed at the test compared with the control sites both at the premolar and molar regions, the differences being statistically significant. The top of the peri-implant mucosa was located more coronally at the control compared with the test sites. The horizontal resorption measured 1mm below the implant shoulder was similar at the test and control sites. Only limited differences were found between premolar and molar sites, with the exclusion of the horizontal resorption that was higher at the test compared with the control sites. A higher alveolar buccal bony crest resorption and a more apical soft tissue marginal position should be expected, when implants are surrounded with thin alveolar mucosa at the time of installation, independently of the thickness of the buccal bony crest.

Tobacco consumption induces alveolar crest height loss independently of mandibular bone mass and bone density

To investigate the relationship of tobacco consumption with alveolar crest height (ACH) loss and mandibular bone mass estimated by digital panoramic radiography and cone-beam computed tomography (CBCT). We studied 315 patients (43.2% [n=136] men and 56.8% [n=179] women) with mean age of 36.6±5.3 (range 21-30years (16.2%), range 31-46years (83.8%); 9% (n=71) were smokers (>10cig./day). A mean of 13.0±2.0 mandibular teeth were present: 37.5% of patients had 6-12 teeth and 62.5% 13-16 teeth. We analyzed 315 digital panoramic radiographs (2D) and calculated the ACH, mandibular cortical width, and basal and alveolar bone gray level values. ACH and bone density were also measured on CBCT (3D) in the 110 patients scheduled for implantation. In the univariate analysis, ACH loss was greater in older patients (P=0.012) and in those with fewer mandibular teeth (P<0.001) and showed a relationship with tobacco consumption that was close to significant (P=0.079). In the multivariate analysis, the number of mandibular teeth (P<0.001) and tobacco consumption (P=0.048) were significantly associated with ACH. Alveolar and basal bone densities were associated, respectively, with number of mandibular teeth (P=0.012) and cortical width (P=0.030). In a Caucasian population aged 21-46years, tobacco consumption was significantly associated with ACH loss. However, ACH loss showed no significant relationship with mandibular bone mass estimated either as mandibular cortical width index or bone density on digital panoramic radiographs or as bone density on CBCT. ACH loss was a local event independent of mandibular bone mass status.

Probe-based confocal laser endomicroscopy of the respiratory tract: A data consistency analysis

Probe-based confocal laser endomicroscopy is a novel imaging tool in the field of respiratory medicine. It enables a real-time and bedside qualitative characterization at the level of small airways but due to a relatively small field of view the reliability of quantification remains uncertain. Twenty-six lung transplant recipients were subjected to two consecutive alveoloscopic imaging procedures within a median time interval of 90 days to analyze test-retest reliability. Only patients in a stable clinical condition were analyzed. We studied alveolar duct diameter, elastic fiber thickness at the alveolar level, the number of autofluorescent cells at the level of the alveolar space, the diameter of autofluorescent alveolar cells and their autofluorescence intensity. Intraclass correlation coefficients ranged from 0.56 for elastic fiber thickness, 0.62 for alveolar duct diameter, 0.29 for alveolar cell diameter, 0.74 for cellularity to 0.78 for alveolar cell autofluorescence. Probe-based confocal laser endomicroscopy enables imaging and quantitative measurements at the level of small airways and alveolar ducts. Test-retest reliability is good for cellularity and autofluorescence quantification but only moderate for morphometric analysis of elastic fibers and alveolar ducts.

Ronald Ogier Ward, urologist, hero &amp; first president of BAUS

Ronald Ogier Ward, urologist, hero &amp; first president of <scp>BAUS</scp>

To BIS or Not to BIS

To the Editor:I read with interest the study by Mashour et al.1 The authors are to be congratulated for having performed this large randomized trial to answer an important question regarding the utility of bispectral index monitor and comparing that to minimum alveolar concentration level alarm system.There are few points that warrant clarification. First, the author included patients who received total intravenous anesthesia. However, the details of this subgroup of patients were not provided. The method of determining the minimum alveolar concentration level in the no bispectral index total intravenous anesthesia patients, the alarm limits, and the incidence of awareness in these patients were not described.Second, the inter-rater agreement using Fleiss κ statistic for the three blinded assessments of awareness showed fair agreement (0.25). Can the authors comment on the low level of agreement and provide the confidence interval for κ?Third, 36% of patients did not have bispectral index data recorded because of technical issues. While this could provide a third arm for comparison, it may also create some bias. Providers who did not receive an alarm might have decreased vigilance as they could have depended on the alarm system. Adding a third arm of routine care in the design might have provided valuable information.Finally, it would have been interesting to learn more about the 19 definite awareness cases in this large sample which could help in refining the characteristics of high-risk patients.

Bayesian inference of the lung alveolar spatial model for the identification of alveolar mechanics associated with acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is acute lung failure secondary to severe systemic inflammation, resulting in a derangement of alveolar mechanics (i.e. the dynamic change in alveolar size and shape during tidal ventilation), leading to alveolar instability that can cause further damage to the pulmonary parenchyma. Mechanical ventilation is a mainstay in the treatment of ARDS, but may induce mechano-physical stresses on unstable alveoli, which can paradoxically propagate the cellular and molecular processes exacerbating ARDS pathology. This phenomenon is called ventilator induced lung injury (VILI), and plays a significant role in morbidity and mortality associated with ARDS. In order to identify optimal ventilation strategies to limit VILI and treat ARDS, it is necessary to understand the complex interplay between biological and physical mechanisms of VILI, first at the alveolar level, and then in aggregate at the whole-lung level. Since there is no current consensus about the underlying dynamics of alveolar mechanics, as an initial step we investigate the ventilatory dynamics of an alveolar sac (AS) with the lung alveolar spatial model (LASM), a 3D spatial biomechanical representation of the AS and its interaction with airflow pressure and the surface tension effects of pulmonary surfactant. We use the LASM to identify the mechanical ramifications of alveolar dynamics associated with ARDS. Using graphical processing unit parallel algorithms, we perform Bayesian inference on the model parameters using experimental data from rat lung under control and Tween-induced ARDS conditions. Our results provide two plausible models that recapitulate two fundamental hypotheses about volume change at the alveolar level: (1) increase in alveolar size through isotropic volume change, or (2) minimal change in AS radius with primary expansion of the mouth of the AS, with the implication that the majority of change in lung volume during the respiratory cycle occurs in the alveolar ducts. These two model solutions correspond to significantly different mechanical properties of the tissue, and we discuss the implications of these different properties and the requirements for new experimental data to discriminate between the hypotheses.

Abstract 3606: Effect of anatase type nanosized titanium dioxide particles on the rat lung and cultured macrophage.

Abstract Nanosized titanium dioxide is mainly categorized into anatase type (anatase type nTiO2) and rutile type (rutile type nTiO2), and widely used in industry, commercial products and biosystems. Previous our report indicated that rutile type nTiO2 caused the growth of A549 human lung carcinoma cells, induction of macrophage, an increase of 8-hydroxydeoxyguanosine (8-OHdG) and overexpression of Macrophage inflammatory protein 1α(MIP1α). Furthermore, under ultraviolet irradiation, anatase type nTiO2 is 100 times more toxic than rutile type nTiO2 in vitro. In the present study, we compared the pulmonary toxic effects induced by anatase type nTiO2 and rutile type nTiO2. Female SD rats were treated with anatase type nTiO2 or rutile type nTiO2 by intrapulmonary spraying for 8 times over a two week period. Obvious lung inflammation foci were not observed in the rats treated with anatase type nTiO2 or rutile type nTiO2. Infiltration of alveolar macrophages was observed throughout the lung tissues and anatase type nTiO2 or rutile type nTiO2 particles were exclusively phagocytosed by alveolar macrophages. Treatment with both anatase type nTiO2 and rutile type nTiO2 also increased number of alveolar macrophage and the production of 8-OHdG in the lung tissue, with a littler higher in the rutile type nTiO2 treated group than in the anatase type nTiO2 treated group. Importantly, expression of MIP1α in the lung tissue treated with anatase type nTiO2 and rutile type nTiO2 as either mRNA level and protein level was significantly up-regulated compared with that of the control group, with significantly lower in the anatase type nTiO2 treated group than in the rutile type nTiO2 treated group. Similarly, anatase type nTiO2 induced significantly lower mRNA expression of MIP1α in primary alveolar macrophages (PAM) and protein level of MIP1α in the supernatants of PAM cell culture than rutile type nTiO2. Additionally, supernatants of PAM cell culture treated with anatase type nTiO2 had less effect on the growth of A549 cell than those treated with rutile type nTiO2. Conclusively, treatment with both anatase type nTiO2 and rutile type nTiO2 did not cause notable lung inflammation. Analysis of alveolar macrophage induction, production of 8-OHdG in the lung tissue, and MIP1α expression both in vivo in the lung and in vitro in PAM indicated that anatase type nTiO2 was less effective than rutile type nTiO2, partly due to low photocatalytic effect in the lung tissue. Citation Format: Takamasa Numano, Jiegou Xu, Mitsuru Futakuchi, Katsumi Fukamachi, Fumio Furukawa, Masumi Suzui, Hiroyuki Tsuda. Effect of anatase type nanosized titanium dioxide particles on the rat lung and cultured macrophage. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3606. doi:10.1158/1538-7445.AM2013-3606

Alcohol causes alveolar epithelial oxidative stress by inhibiting the nuclear factor (erythroid-derived 2)-like 2-antioxidant response element signaling pathway.

Excessive alcohol use increases the risk of acute lung injury and pneumonia. Chronic alcohol ingestion causes oxidative stress within the alveolar space, including near depletion of glutathione (GSH), which impairs alveolar epithelial and macrophage function, in experimental animals and human subjects. However, the fundamental mechanism(s) by which alcohol induces such profound lung oxidative stress is unknown. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a redox-sensitive master transcription factor that regulates activation of the antioxidant response element (ARE). As the alveolar epithelium controls GSH levels within the alveolar space, we hypothesized that alcohol also decreases Nrf2 expression and/or activation within the alveolar epithelium. In this study, we determined that alcohol ingestion in vivo or direct alcohol exposure in vitro down-regulated the Nrf2-ARE pathway in lung epithelial cells, decreased the expression of antioxidant genes, and lowered intracellular GSH levels. RNA silencing of Nrf2 gene expression in alveolar epithelial cells in vitro decreased expression of these same antioxidant genes, and likewise lowered intracellular GSH levels, findings that mirrored the effects of alcohol. In contrast, treating alcohol-exposed alveolar epithelial cells in vitro with the Nrf2 activator, sulforaphane, preserved Nrf2 expression, ARE activation, intracellular GSH levels, and epithelial barrier function. These new experimental findings implicate down-regulation of the Nrf2-ARE signaling pathway as a fundamental mechanism by which alcohol causes profound oxidative stress and alveolar epithelial dysfunction, and suggest that treatments, such as sulforaphane, that activate this pathway could mitigate the pathophysiological consequences of alcohol on the lung and other organs.

Putting Evidence Into Nursing Practice: Four Traditional Practices Not Supported by the Evidence

Evidence-based nursing practice is essential to the delivery of high-quality care that optimizes patients' outcomes. Studies continue to show improved outcomes when best evidence is used in the delivery of patient care. Despite awareness of the importance of practicing by using best evidence, achieving and sustaining evidence-based practice within practice environments can be challenging, and research suggests that integration of evidence-based practice into daily clinical practice remains inconsistent. This article addresses 4 practice issues that, first, are within the realm of nursing and if changed might improve care of patients and, second, are areas in which the tradition and the evidence do not agree and practice continues to follow tradition. The topics addressed are (1) noninvasive measurement of blood pressure in children, (2) oxygen administration for patients with chronic obstructive pulmonary disease, (3) intravenous catheter size and blood administration, and (4) infection control practices to prevent infections. The related beliefs, current evidence, and recommendations for practice related to each topic are described.

Dexamethasone Attenuates VEGF Expression and Inflammation but Not Barrier Dysfunction in a Murine Model of Ventilator–Induced Lung Injury

BackgroundVentilator–induced lung injury (VILI) is characterized by vascular leakage and inflammatory responses eventually leading to pulmonary dysfunction. Vascular endothelial growth factor (VEGF) has been proposed to be involved in the pathogenesis of VILI. This study examines the inhibitory effect of dexamethasone on VEGF expression, inflammation and alveolar–capillary barrier dysfunction in an established murine model of VILI.MethodsHealthy male C57Bl/6 mice were anesthetized, tracheotomized and mechanically ventilated for 5 hours with an inspiratory pressure of 10 cmH2O (“lower” tidal volumes of ∼7.5 ml/kg; LVT) or 18 cmH2O (“higher” tidal volumes of ∼15 ml/kg; HVT). Dexamethasone was intravenously administered at the initiation of HVT–ventilation. Non–ventilated mice served as controls. Study endpoints included VEGF and inflammatory mediator expression in lung tissue, neutrophil and protein levels in bronchoalveolar lavage fluid, PaO2 to FiO2 ratios and lung wet to dry ratios.ResultsParticularly HVT–ventilation led to alveolar–capillary barrier dysfunction as reflected by reduced PaO2 to FiO2 ratios, elevated alveolar protein levels and increased lung wet to dry ratios. Moreover, VILI was associated with enhanced VEGF production, inflammatory mediator expression and neutrophil infiltration. Dexamethasone treatment inhibited VEGF and pro–inflammatory response in lungs of HVT–ventilated mice, without improving alveolar–capillary permeability, gas exchange and pulmonary edema formation.ConclusionsDexamethasone treatment completely abolishes ventilator–induced VEGF expression and inflammation. However, dexamethasone does not protect against alveolar–capillary barrier dysfunction in an established murine model of VILI.

Small-airways dysfunction associates with respiratory symptoms and clinical features of asthma: A systematic review

Traditionally, asthma has been considered a disease that predominantly involves the large airways. Today, this concept is being challenged, and increasing evidence has become available showing that abnormalities in the small airways also contribute to the clinical expression of asthma. The small airways can be affected by inflammation, remodeling, and changes in the surrounding tissue, all contributing to small-airways dysfunction. In this article we have performed a systematic review of the literature on the association between small-airways dysfunction and clinical signs and symptoms of asthma. This review shows that small-airways dysfunction associates with worse control of asthma, higher numbers of exacerbations, the presence of nocturnal asthma, more severe bronchial hyperresponsiveness, exercise-induced asthma, and the late-phase allergic response. Importantly, small-airways dysfunction can already be present in patients with mild asthma. Our review provides suggestive evidence that a better response of the small airways to inhaled steroids or montelukast associates with better asthma control. For this reason, an early recognition of small-airways dysfunction is important because it enables the physician to start timely treatment to target the small airways. It is important to develop simpler and more reliable tools (eg, questionnaires or bronchial provocation tests with small-particle stimuli) to assess the presence and extent of small-airways dysfunction in daily clinical practice.

Pulmonary toxicity of instilled cadmium-doped silica nanoparticles during acute and subacute stages in rats.

Potential risk associated with new nanomaterial exposure needs to be assessed. This in vivo study investigated pulmonary effects of engineered cadmium-containing silica nanoparticles Cd/SiNPs (1 mg/rat), silica SiNPs (600 μg/rat) and CdCl₂ (400 μg/rat) 1, 7 and 30 days after intratracheal instillation. Comprehensive histopathological and immunocytochemical characterization of lung damage in terms of apoptosis, cell proliferation, inflammation, fibrosis and metabolism were obtained. After exposure to all treatments, lung parenchyma showed injury patterns characterized by collapsed alveoli, inflammation, granuloma formation, thickened alveolar septa and bronchiolar epithelium exfoliation. Type II pneumocytes, containing scarcely surfactant-lamellated bodies, were also observed. Apoptotic phenomena enhanced as following, Cd/SiNPs>CdCl₂> SiNPs. In parallel with these findings, a significant increase of PCNA-immunoreactive cells was detected together with high mitotic activity. Cellular localization and distribution of IL-6, IP-10 and TGF-β1 revealed an increased expression of these cytokines as evidence of an enhanced cellular inflammatory response. CYP450-immunoreactivity was also enhanced, at bronchiolar (e.g. Clara cells) and alveolar (e.g. macrophages) level after both Cd/SiNPs and CdCl₂. These overall effects were observed acutely and lasted until the 30th day, with Cd/SiNPs producing the most marked effects. Collagen-immunolabelling changed particularly 7 and 30 days after Cd/SiNPs, when a strong stromal fibrogenic reaction occurred. The present findings suggest that Cd/SiNPs produce significantly greater pulmonary alterations than either SiNPs or CdCl₂ under the present experimental conditions.