[A systematic review and Meta-analysis of Tongfu Xiefei method in the treatment of acute respiratory distress syndrome].

OBJECTIVE: To systematically review the effect of Tongfu Xiefei method on prognosis and respiratory mechanics parameters in patients with acute respiratory distress syndrome (ARDS). METHODS: The randomized controlled trials (RCT) of Tongfu Xiefei method for ARDS published on PubMed, Web of Science, Embase, CNKI and Wanfang database from January 1st 2001 to June 30th 2019 were searched. Conventional treatment for ARDS that included mechanical ventilation, prone ventilation, anti-infection, organ function maintenance and nutritional therapy were used in the control group. While the Tongfu Xiefei method was applied in the experimental group based on the conventional treatment. The main outcome was in-hospital mortality, and the secondary outcomes included mechanic ventilation time, length of intensive care unit (ICU) stay and respiratory mechanics parameters. Two researchers independently searched the literature, collected data and assessed the risk of bias. The bias risk assessment was completed by RevMan 5.3 software. The Meta-analysis was completed by R software. The potential publication bias of main outcome was evaluation. RESULTS: A total of 27 RCTs were included. There were 1 763 patients, including 899 in the experimental group and 864 in the control group. Meta-analysis showed that, compared with the control group, the in-hospital mortality of the experimental group significantly decreased [relative risk (RR) = 0.46, 95% confidence interval (95%CI) was 0.36 to 0.59, P < 0.000 1], the mechanic ventilation time and the length of ICU stay were significantly shortened [mechanical ventilation time: standard mean difference (SMD) = -1.92, 95%CI was -2.56 to -1.29, P < 0.000 1; length of ICU stay: SMD = -1.84, 95%CI was -2.49 to -1.18, P < 0.000 1], oxygenation index was significantly improved (SMD = 2.26, 95%CI was 1.56 to 2.96, P < 0.000 1), airway peak pressure, airway platform pressure, mean airway pressure and airway resistance significantly decreased (airway peak pressure: SMD = -1.26, 95%CI was -2.35 to -0.18, P = 0.021 8; airway platform pressure: SMD = -0.61, 95%CI was -1.08 to -0.14, P = 0.010 7; mean airway pressure: SMD = - 1.67, 95%CI was - 2.93 to -0.42, P = 0.009 1; airway resistance: SMD = -0.88, 95%CI was -1.09 to -0.67, P < 0.000 1), while lung compliance increased (SMD = 1.57, 95%CI was 0.78 to 2.36, P < 0.000 1). The results of publication bias assessment showed that there was no potential publication bias (P = 0.499). CONCLUSIONS: Tongfu Xiefei method is capable of reducing the in-hospital mortality, shortening the mechanical ventilation time and the length of ICU stay, and improving respiratory mechanics parameters for patients with ARDS.

Acupoint Catgut Embedding Improves the Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Rats.

BACKGROUND: This study investigated the potential therapeutic effects of acupoint catgut embedding (ACE) at ST36 and BL13 on lipopolysaccharide- (LPS-) induced acute respiratory distress syndrome (ARDS) in rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomized into the normal saline (NS group with a sham procedure), lipopolysaccharide (LPS group with a sham procedure), and LPS plus ACE (LPS+ACE with ACE at bilateral BL13 and ST36 acupoints one day before LPS injection) groups. After intratracheal instillation of normal saline or LPS (0.5 mg/kg), all rats were subjected to mechanical ventilation for 4 h. Their blood gas was analyzed before and after lung injury, and their lung pressure-volumes were measured longitudinally. The levels of TNF-α, IL-6, IL-10, and phosphatidylcholine (PC) and total proteins (TP) in bronchial alveolar lavage fluid (BALF) were assessed. Their wet to dry lung weight ratios, histology, myeloperoxidase (MPO), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) levels were measured. Their lung aquaporin 1 (AQP1) and Occludin protein levels were analyzed. RESULTS: LPS administration significantly decreased the ratios of PaO2/FiO2 and pressure-volumes and induced lung inflammation and injury by increased concentrations of TNF-α, IL-6, IL-10, and TP in BALF and MPO and MDA in the lung but decreased PC in BALF and SOD activity in the lungs. LPS also reduced AQP1 and Occludin protein levels in the lung of rats. In contrast, ACE significantly mitigated the LPS-induced lung injury, inflammation, and oxidative stress and preserved the AQP1 and Occludin contents in the lung of rats. CONCLUSIONS: ACE significantly improved respiratory function by mitigating inflammation and oxidative stress and preserving AQP1 and Occludin expression in the lung in a rat model of LPS-induced ARDS.

Fibrotic microtissue array to predict anti-fibrosis drug efficacy.

Fibrosis is a severe health problem characterized by progressive stiffening of tissues which causes organ malfunction and failure. A major bottleneck in developing new anti-fibrosis therapies is the lack of in vitro models that recapitulate dynamic changes in tissue mechanics during fibrogenesis. Here we create membranous human lung microtissues to model key biomechanical events occurred during lung fibrogenesis including progressive stiffening and contraction of alveolar tissue, decline in alveolar tissue compliance and traction force-induced bronchial dilation. With these capabilities, we provide proof of principle for using this fibrotic tissue array for multi-parameter, phenotypic analysis of the therapeutic efficacy of two anti-fibrosis drugs recently approved by the FDA. Preventative treatments with Pirfenidone and Nintedanib reduce tissue contractility and prevent tissue stiffening and decline in tissue compliance. In a therapeutic treatment regimen, both drugs restore tissue compliance. These results highlight the pathophysiologically relevant modeling capability of our novel fibrotic microtissue system.

[Clinical abservations of pulmonary surfactant' s autologous transfusion in massive lung lavage].

Objective: Investigate the pulmonary surfactant autotransfusion effect on the recovery of respiratory function in patients with whole lung lavage, to provide theoretical basis for the clinical application. Methods: We taken 30 patients of pneumoconiosis treated by whole lung lavage as the subjects. We extracted the pulmonary surfactant from lavage fluid, after single postoperative lung lavage for the first time; after one weeks when the second times of lung lavage were performed to the other side of the lung of patients, we put PS into the right side. We taken the patients the second times of lung lavage who were put PS into the right side as returning group, the first times of lung lavage who were not put PS into as on returning group. We observed indi-cators, such as expiratory resistance, respiratory work, lung compliance, airway pressure, PO(2), the pulmonary function recovery time and other indicators, comparing with the changes of pulmonary function before lung la-vage for the first time and at 0、60、90、120 min after the pulmonary surfactant autotransfusion. Results: Com-pared with the no returning group, the expiratory resistance of the returning group decreased significantly at 90 min、120 min after the pulmonary surfactant autotransfusion; the respiratory work and airway pressure of the re-turning group decreased significantly at 60、90、120 min after the pulmonary surfactant autotransfusion, there was statistically significant in the difference between different groups (P<0.05, P<0.01). Compared with the no returning group, the lung compliance and the PO(2) of the returning group increased significantly at 60 min、90 min、120 min after the pulmonary surfactant autotransfusion, there was statistically significant in the difference between different groups (P<0.05, P<0.01). The lung function recovery time of returning group was (155.7 ± 35.2) min, the lung function recovery time of no returning group was (183.71±41.81) min, there was statistical-ly significant in the difference between different groups (P<0.05). Compared with the no returning, there were not statistically significant in the difference of the Heart rate、the systolic blood pressure and the diastolic blood pressure about the returning at 60、90、120 min after the pulmonary surfactant autotransfusion.There was no ad-verse reactions such as pulmonary infection, pulmonary infection and so on. Conclusion: The pulmonary surfac-tant autotransfusion may reduce expiratory resistance, work of breathing, airway pressure; improve lung compliance, alveolar ventilation function; increase oxygen partial pressure and decrease the surgery recovery time in patients with pneumoconiosis.

Effects of Xuanbai Chengqi decoction on lung compliance for patients with exogenous pulmonary acute respiratory distress syndrome.

OBJECTIVE: To observe the effects of Xuanbai Chengqi decoction on lung compliance for patients with exogenous pulmonary acute respiratory distress syndrome. SUBJECTS AND METHODS: A total of 53 patients with exogenous pulmonary acute respiratory distress syndrome, who were admitted to the intensive care unit of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine from March 2009 to February 2013, were selected. They were randomly divided into the treatment group (25 cases) and the control group (28 cases). Both the groups were treated with conventional treatment and lung-protective ventilation strategy; apart from these, enema therapy with Xuanbai Chengqi decoction was given to the treatment group. Meanwhile, static lung compliance, dynamic lung compliance, peak airway pressure, plateau pressure, and positive end-expiratory pressure (PEEP) for patients in both the groups were observed and recorded at 24, 48, and 72 hours after the drug was used. Moreover, variations in the duration of parenteral nutrition, incidence rate of complications, and case fatality rate in patients after treatment were recorded. RESULTS: For patients in the treatment group, at 48 and 72 hours after treatment, the static lung compliance and dynamic lung compliance were significantly higher than those in the control group, while plateau pressure, peak airway pressure, and PEEP were significantly lower than those before treatment. At the same time, PEEP for patients in the treatment group at 72 hours after treatment was remarkably lower than that in the control group, showing significant difference (P<0.05). The duration of parenteral nutrition in the treatment group was significantly shorter than that in the control group (P<0.05). Both the incidence rate and the fatality rate of complications, such as abdominal distension and ventilator-associated pneumonia, for patients in the treatment group were distinctly smaller than those in the control group (P<0.05). CONCLUSION: Xuanbai Chengqi decoction not only can improve the static lung compliance and dynamic compliance of patients with exogenous pulmonary distress syndrome but also can shorten the parenteral nutrition duration, as well as reducing the complication incidence rate and fatality rate.

Metabolomics screening identifies reduced L-carnitine to be associated with progressive emphysema.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, small airway remodelling and emphysema. Emphysema is the destruction of alveolar structures, leading to enlarged airspaces and reduced surface area impairing the ability for gaseous exchange. To further understand the pathological mechanisms underlying progressive emphysema, we used MS-based approaches to quantify the lung, bronchoalveolar lavage fluid (BALF) and serum metabolome during emphysema progression in the established murine porcine pancreatic elastase (PPE) model on days 28, 56 and 161, compared with PBS controls. Partial least squares (PLS) analysis revealed greater changes in the metabolome of lung followed by BALF rather than serum during emphysema progression. Furthermore, we demonstrate for the first time that emphysema progression is associated with a reduction in lung-specific L-carnitine, a metabolite critical for transporting long-chain fatty acids into the mitochondria for their subsequent ß-oxidation. In vitro, stimulation of the alveolar epithelial type II (ATII)-like LA4 cell line with L-carnitine diminished apoptosis induced by both PPE and H2O2. Moreover, PPE-treated mice demonstrated impaired lung function compared with PBS-treated controls (lung compliance; 0.067±0.008 ml/cmH20 compared with 0.035±0.005 ml/cmH20, P<0.0001), which improved following supplementation with L-carnitine (0.051±0.006, P<0.01) and was associated with a reduction in apoptosis. In summary, our results provide a new insight into the role of L-carnitine and, importantly, suggest therapeutic avenues for COPD.

Low forced expiratory flow rates and forceful exhalation as a cause for arterial gas embolism during submarine escape training: a case report.

A 26-year-old male U.S. Navy submariner suffered an arterial gas embolism during pressurized submarine escape training. Routine pretraining medical screening revealed no history of asthma, pneumothorax or recent respiratory infection. Pulmonary function testing and posterioranterior/lateral chest X-ray were normal. He forcefully exhaled at the start of his ascent and developed neurological abnormalities including lightheadedness with lower extremity weakness and paresthesias after surfacing. He fully recovered after a U.S. Navy Treatment Table 6. This case represents the first report of an arterial gas embolism since the U.S. Navy resumed pressurized submarine escape training utilizing the Submarine Escape and Immersion Equipment suit. We discuss possible contributing factors and propose that his AGE was caused by pulmonary barotrauma due to a combination of low forced expiratory flow rates and an overly forceful exhalation during his ascent.

Medicinas tradicionales andinas y su despenalización: entrevista con Walter Álvarez Quispe / Decriminalizing traditional Andean medicine: an interview with Walter Álvarez Quispe

Walter Álvarez Quispe, terapeuta kallawaya y biomédico especializado en cirugía general y ginecología, presenta la lucha de los terapeutas tradicionales y alternativos por la depenalización de estos sistemas médicos andinos realizada entre 1960 y 1990. Bolivia se torna el primer país en América Latina y el Caribe en despenalizar la medicina tradicional antes de los planteamientos de la Conferencia Internacional sobre Atención Primaria de Salud (Alma-Ata, 1978). Los datos aportados por el entrevistado aseguran que los logros alcanzados, principalmente por los kallawayas, responden a un proyecto propio y autónomo. Estas conquistas no se deben a las políticas oficiales de interculturalidad en salud, aunque busquen atribuirse para sí los logros alcanzados.

Walter Álvarez Quispe, a Kallawaya healer and biomedical practitioner specializing in general surgery and gynecology, presents the struggle of traditional and alternative healers to get their Andean medical systems depenalized between 1960 and 1990. Bolivia was the first country in Latin America and the Caribbean to decriminalize traditional medicine before the proposals of the International Conference on Primary Health Care (Alma-Ata, 1978). The data provided by the interviewee show that the successes achieved, mainly by the Kallawayas, stem from their own independent initiative. These victories are not the result of official policies of interculturality in healthcare, although the successes achieved tend to be ascribed to them.

A review of recent findings about stress-relaxation in the respiratory system tissues.

This article reviews the state of the art about an unclear physiological phenomenon interesting respiratory system tissues, i.e., stress-relaxation. Due to their visco-elastic properties, the tissues do not maintain constant stress under constant deformation. Rather, the stress slowly relaxes and falls to a lower value. The exact molecular basis of this complex visco-elastic behavior is not well defined, but it has been suggested that it may be generated because of the anisotropic mechanical properties of elastin and collagen fibers in the alveolar septa and their interaction phenomena, such as reciprocal sliding, also in relation to interstitial liquid movements. The effects on stress-relaxation of various biochemical and physical factors are reviewed, including the consequences of body temperature variations, respiratory system inflammations and hyperbaric oxygen exposure, endocrinal factors, circulating blood volume variations, changes in inflation volume and/or flow, changes in intra-abdominal pressure because of pneumoperitoneum or Trendelenburg position. The effects of these factors on stress-relaxation have practical consequences because, depending on visco-elastic pressure amount which is requested to inflate the respiratory system in different conditions, respiratory muscles have to produce different values of inspiratory pressure during spontaneous breathing. High inspiratory pressure values might increase the risk of respiratory failure development on mechanical basis.

The volume dependence of stress relaxation in the rat respiratory system.

AIM: To investigate the volume dependence of respiratory system stress relaxation in anesthetized, positive-pressure ventilated rats. MATERIALS AND METHODS: The effects on respiratory system stress relaxation of changing the end inflation volume while keeping tidal volume constant, and of changing the tidal volume while maintaining constant end inflation volume, were separately studied by the end-inflation occlusion method. These changes were obtained by inflating the respiratory system starting from different volumes above functional residual capacity. RESULTS: We found that: (1) a simple exponential equation well describe the visco-elastic pressure drop for different inflation modalities; (2) the stress relaxation-linked, visco-elastic pressure drop, increases with increasing the tidal volume and keeping the end-inflation volume constant, but is independent from the end-inflation lung volume at constant tidal volumes; (3) time constant values show a significant increment with end-inflation volume at constant tidal volume but result independent from tidal volume variation at constant end-inflation volume. CONCLUSIONS: Stress relaxation-linked pressure dissipation increases with increasing tidal volume independently from end-inspiratory volume.

Anti-asthmatic effects of baicalin in a mouse model of allergic asthma.

The aim of the study was to investigate the anti-asthmatic effects of baicalin (BA) and the possible mechanisms. Asthma model was established by ovalbumin (OVA) intraperitoneal injection. A total of 60 mice were randomly assigned to six experimental groups: control, model, dexamethasone (2 mg/kg), and BA (10 mg/kg, 20 mg/kg, 40 mg/kg). Airway resistance (RI) and lung compliance (Cdyn) were measured, histological studies were evaluated by the hematoxylin and eosin staining, Th1/Th2, OVA-specific serum, and BALF IgE levels and Th17 cytokines were evaluated by enzyme-linked immunosorbent assay, and Th17 cells was evaluated by flow cytometry (FCM). Our study demonstrated that BA inhibited OVA-induced increases in RI and eosinophil count; interleukin (IL)-4, IL-17A levels, and Cdyn were recovered and increased IFN-γ level in bronchoalveolar lavage fluid. Histological studies demonstrated that BA substantially inhibited OVA-induced eosinophilia in lung tissue and airway tissue. FCM studies demonstrated that BA substantially inhibited Th17 cells. These findings suggest that BA may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma.

[Effect of flavonoids from hedysari radix on pulmonary functions of pulmonary fibrosis rat].

OBJECTIVE: To study the effect of flavonoids from Hedysari Radix on pulmonary functions of pulmonary fibrosis rat and its mechanism. METHODS: 72 Wistar rats were randomly divided into 6 groups: blank control group, model group, prednisone group, Hedysari Radix flavonoids low, medium and high dosage group. The rat model was established by propelling bleomycin into bronchial tree through endotracheal intubation with laryngoscope. The pulmonary fanctions were measured. RESULTS: Hedysari Radix flavonoids could normalize the pulmonary functions of rats with bleomycin-induced pulmonary fibrosis. CONCLUSION: Hedysari Radix flavonoids can inhibit the process of pulmonary fibrosis.

The effectiveness of fish oil supplementation in asthmatic rats is limited by an inefficient action on ASM function.

Episodes of acute exacerbation are the major clinical feature of asthma and therefore represent an important focus for developing novel therapies for this disease. There are many reports that the n-3 fatty acids found in fish oil exert anti-inflammatory effects, but there are few studies of the action of fish oil on airway smooth muscle (ASM) function. In the present investigation, we evaluated the effect of fish oil supplementation on smooth muscle force of contraction in ovalbumin-induced asthmatic Wistar rats, and its consequences on static lung compliance, mucus production, leukocyte chemotaxis and production of proinflammatory cytokines. Fish oil supplementation suppressed the infiltration of inflammatory cells into the lung in asthmatic animals (2.04 ± 0.19 × 10(6) cells vs. 3.33 ± 0.43 × 10(6) cells in the control asthmatic group; P < 0.05). Static lung compliance increased with fish oil supplementation in asthmatic rats (0.640 ± 0.053 mL/cm H2O vs. 0.399 ± 0.043 mL/cm H2O; P < 0.05). However, fish oil did not prevent asthma-associated lung eosinophilia and did not affect the concentrations of tumor necrosis factor-α and interleukin-1ß in lung tissue or the proportion of the airways obliterated with mucus. Fish oil had no effect on the force of contraction in asthmatic rats in response to acetylcholine (3.026 ± 0.274 mN vs. 2.813 ± 0.364 mN in the control asthmatic group). In conclusion, although fish oil exerts some benefits in this model of asthma, its effectiveness appears to be limited by an inefficient action on airway smooth muscle function.

[Study of novel artificial lung surfactants incorporating partially fluorinated amphiphiles].

Lung surfactants (LS), a complex of ∼90 wt% lipids (mainly dipalmitoylphosphatidylcholine or DPPC) and ∼10 wt% surfactant proteins (SP-A, -B, -C, and -D), adsorb to an air-alveolar fluid interface and then lower its surface tension down to near zero during expiration. Intratracheal instillation of exogenous LS preparations can effectively compensate for surfactant deficiency in premature infants with respiratory distress syndrome (RDS). Surfacten® (Mitsubishi Tanabe Pharma Corporation, Osaka, Japan), a modified bovine lung extract and an effective surfactant replacement in treatment for RDS patients, is supplemented with DPPC, palmitic acid, and tripalmitin. For the premature infants suffering from RDS, instillation of Surfacten® leads to a dramatic improvement in lung function and compliance. Herein, the author reviews potential use of newly designed preparations containing a mimicking peptide of SP-B and also introduces the current research on the preparations incorporated with partially fluorinated amphiphiles to improve their efficacy.

Role of airway recruitment and derecruitment in lung injury.

The mechanical forces generated during the ventilation of patients with acute lung injury causes significant lung damage and inflammation. Low-volume ventilation protocols are commonly used to prevent stretch-related injury that occurs at high lung volumes. However, the cyclic closure and reopening of pulmonary airways at low lung volumes, i.e., derecruitment and recruitment, also causes significant lung damage and inflammation. In this review, we provide an overview of how biomedical engineering techniques are being used to elucidate the complex physiological and biomechanical mechanisms responsible for cellular injury during recruitment/derecruitment. We focus on the development of multiscale, multiphysics computational models of cell deformation and injury during airway reopening. These models, and the corresponding in vitro experiments, have been used to both elucidate the basic mechanisms responsible for recruitment/derecruitment injury and to develop alternative therapies that make the epithelium more resistant to injury. For example, models and experiments indicate that fluidization of the cytoskeleton is cytoprotective and that changes in cytoskeletal structure and cell mechanics can be used to mitigate the mechanotransduction of oscillatory pressure into inflammatory signaling. The continued application of biomedical engineering techniques to the problem of recruitment/derecruitment injury may therefore lead to novel and more effective therapies.

Pulmonary function and histological impairment in mice after acute exposure to aluminum dust.

Along the aluminum refining process, alumina (Al2O3) constitutes the main source of dust. Although aluminum refinery workers present respiratory symptoms with lung functional changes, no conclusive data about lung function impairment after alumina exposure has been so far reported. We examined the pulmonary alterations of exposure to material collected in an aluminum refinery in Brazil. BALB/c mice were exposed in a whole-body chamber for 1 h to either saline (CTRL, n = 11) or to a suspension (in saline) of 8 mg/m(3) of the dust (ALUM, n = 11) both delivered by an ultrasonic nebulizer. Twenty-four hours after exposure lung mechanics were measured by the end-inflation method. Lungs were prepared for histology. ALUM showed significantly higher static elastance (34.61 +/- 5.76 cmH2O/mL), elastic component of viscoelasticity (8.16 +/- 1.20 cmH2O/mL), pressure used to overcome the resistive component of viscoelasticity (1.62 +/- 0.24 cmH2O), and total resistive pressure (2.21 +/- 0.49 cmH2O) than CTRL (27.95 +/- 3.63 cmH2O/mL, 6.12 +/- 0.99 cmH2O/mL, 1.23 +/- 0.19 cmH2O, and 1.68 +/- 0.23 cmH2O, respectively). ALUM also presented significantly higher fraction area of alveolar collapse (69.7 +/- 1.2%) and influx of polymorphonuclear cells (27.5 +/- 1.1%) in lung parenchyma than CTRL (27.2 +/- 1.1% and 14.6 +/- 0.7%, respectively). The composition analysis of the particulate matter showed high concentrations of aluminum. For the first time it was demonstrated in an experimental model that an acute exposure to dust collected in an aluminum producing facility impaired lung mechanics that could be associated with inflammation.

Intracerebroventricular injection of leukotriene B4 attenuates antigen-induced asthmatic response via BLT1 receptor stimulating HPA-axis in sensitized rats.

BACKGROUND: Basic and clinical studies suggest that hypothalamic-pituitary-adrenal (HPA) axis is the neuroendocrine-immune pathway that functionally regulates the chronic inflammatory disease including asthma. Our previous studies showed corresponding changes of cytokines and leukotriene B4 (LTB4) between brain and lung tissues in antigen-challenged asthmatic rats. Here, we investigated how the increased LTB4 level in brain interacts with HPA axis in regulating antigen-induced asthmatic response in sensitized rats. METHODS: Ovalbumin-sensitized rats were challenged by inhalation of antigen. Rats received vehicle, LTB4 or U75302 (a selective LTB4 BLT1 receptor inhibitor) was given via intracerebroventricular injection (i.c.v) 30 min before challenge. Lung resistance (RL) and dynamic lung compliance (Cdyn) were measured before and after antigen challenge. Inflammatory response in lung tissue was assessed 24 h after challenge. Expression of CRH mRNA and protein in hypothalamus were evaluated by RT-PCR and Western Blot, and plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were measured using the ELISA kits. RESULTS: Antigen challenge decreased pulmonary function and induced airway inflammation, evoked HPA axis response in sensitized rats. Administration of LTB4 via i.c.v markedly attenuated airway contraction and inflammation. Meanwhile, LTB4 via i.c.v markedly increased CORT and ACTH level in plasma before antigen challenge, and followed by further increases in CORT and ACTH levels in plasma after antigen challenge in sensitized rats. Expression of CRH mRNA and protein in hypothalamus were also significantly increased by LTB4 via i.c.v in sensitized rats after antigen challenge. These effect were completely blocked by pre-treatment with BLT1 receptor antagonist U75302 (10 ng), but not by BLT2 antagonist LY255283. CONCLUSIONS: LTB4 administered via i.c.v down-regulates the airway contraction response and inflammation through activation of the HPA axis via its BLT1 receptor. This study expands our concept of the regulatory role of intracranial inflammatory mediators in inflammatory diseases including asthma. The favourable effects of LTB4 on the HPA axis may help to explain the phenomenon of self-relief after an asthmatic attack.

Surfactant pretreatment decreases long-term damage after ischemia-reperfusion injury of the lung.

OBJECTIVE: Lung ischemia-reperfusion injury (LIRI) is a risk factor for primary acute graft failure following lung transplantation. LIRI hereby contributes to morbidity and mortality after lung transplantation. We have previously shown that surfactant pretreatment ameliorates LIRI up to 1 week after reperfusion. However, the impact of surfactant pretreatment on long-term outcome following LIRI is unknown. Therefore, the objective of this study was to investigate the effect of surfactant pretreatment on long-term outcome following LIRI. METHODS: Male Sprague-Dawley rats (n=63) were randomized to receive intratracheally administered porcine surfactant (400mg/kg) or no pretreatment. One hour thereafter, animals underwent 120min of warm ischemia by clamping the bronchus, pulmonary artery and vein of the left lung. A third group was sham-operated; a fourth group served as unoperated controls. Animals were killed on day 30 or 90 after surgery. Arterial oxygenation and lung compliance were determined. Broncho-alveolar lavage fluid (BALf) was collected to assess surfactant function and alveolar protein. Leukocyte infiltration was determined by flowcytometry in BALf, lung tissue and thoracic lymph nodes. Lungs of three animals per group were used for histological assessment. RESULTS: Lung compliance was lower on day 30 and day 90 after LIRI than in sham-operated controls (day 30 V(max) 6.1+/-2.1 vs 12.6+/-1.3, day 90 6.9+/-3.0 vs 12.1+/-1.6; C(max) day 30 0.49+/-0.17 vs 1.08+/-0.21, day 90 0.67+/-0.31 vs 1.11+/-0.17). Furthermore, the number of CD45RA(+)-lymphocytes in left lung tissue was decreased on day 90 compared to unoperated animals (230.633+/-96.770 vs 696.347+/-202.909) and the number of macrophages elevated in left BALf on day 90. HE slides of LIRI animals were scored as fibroproliferative with moderate atelectasis. Surfactant pretreatment improved lung compliance (V(max) day 30 11.7+/-1.8, day 90 11.1+/-1.2; C(max) day 30 1.04+/-0.23, day 90 1.16+/-0.21) and normalized the number of CD45RA(+)-lymphocytes (769.555+/-421.016) in left lung tissue. Furthermore lung architecture on HE slides was on return to normal. However, more CD5(+)CD4(+)-lymphocytes on day 30 (754.788+/-97.269 vs 430.409+/-109.909) and more macrophages on day 90 (2.144.000+/-630.633 vs 867.454+/-383.220) were measured in pretreated lung tissue compared to LIRI animals. CONCLUSIONS: Severe LIRI caused extensive pulmonary injury up to 90 days postoperatively. Surfactant pretreatment normalized pulmonary function, but resulted in an increased number of CD5(+)CD4(+)-cells and macrophages in lung tissue.

Oxygenation and static compliance is improved immediately after early manual hyperinflation following myocardial revascularisation: a randomised controlled trial.

QUESTION: Are oxygenation and static compliance improved immediately after manual hyperinflation following myocardial revascularisation? Does this lead to earlier extubation and shorter hospital stay? Does it reduce postoperative pulmonary complications? DESIGN: Randomised controlled trial with concealed allocation, blinded assessment and intention-to-treat analysis. PARTICIPANTS: Fifty-five patients who underwent myocardial revascularisation. INTERVENTION: After an hour in recovery, the experimental group received manual hyperinflation with positive end expiratory pressure followed by suction while the control group received suction only. OUTCOME MEASURES: Oxygenation (PaO(2) in mmHg) and static lung compliance (in ml/cmH(2)O) were measured immediately after suction. Time to extubation (in minutes) and length of hospital stay (in days) were collected and postoperative pulmonary complications were confirmed by X-ray. RESULTS: PaO(2) was 11.7 mmHg (95% CI 9.4 to 14.0) greater in the experimental group while static compliance was 8.5 ml/cmH(2)0 (95% CI 6.4 to 10.6) greater than in the control group. The experimental group was extubated 76 minutes (95% CI 24 to 128) earlier than the control group but did not have a shorter length of stay (mean difference 0.5 days, 95% CI -0.2 to 1.2). The relative risk of postoperative pulmonary complications was no greater (RR 0.57, 95% Cl 0.20 to 1.60) in the experimental group than in the control group. CONCLUSION: The group that received early manual hyperinflation had markedly better oxygenation and static compliance as well as shorter mechanical ventilation times than the control group. The length of hospital stay and incidence of postoperative pulmonary complications were similar in the two groups.

Characteristics of the respiratory mechanical and muscle function of competitive breath-hold divers.

Competitive breath-hold divers (BHD) employ glossopharyngeal insufflation (GI) to increase intrapulmonary oxygen stores and prevent the lungs from dangerous compressions at great depths. Glossopharyngeal insufflation is associated with inflation of the lungs beyond total lung capacity (TLC). It is currently unknown whether GI transiently over-distends the lungs or adversely affects lung elastic properties in the long-term. Resting lung function, ventilatory drive, muscle strength, and lung compliance were measured in eight BHD who performed GI since 5.5 (range 2-6) years on average, eight scuba divers, and eight control subjects. In five BHD subsequent measures of static lung compliance (Cstat) were obtained after 1 and 3 min following GI. Breath-hold divers had higher than predicted ventilatory flows and volumes and did not differ from control groups with regard to gas transfer, inspiratory muscle strength, and lung compliance. A blunted response to CO2 was obtained in BHD as compared to control groups. Upon GI there was an increase in mean vital capacity (VCGI) by 1.75 +/- 0.85 (SD) L compared to baseline (p < 0.001). In five BHD Cstat raised from 3.7 (range 2.9-6.8) L/kPa at baseline to 8.1 (range 3.4-21.2) L/kPa after maximal GI and thereafter gradually decreased to 5.6 (range 3.3-8.1) L/kPa after 1 min and 4.2 (range 2.7-6.6) L/kPa after 3 min (p < 0.01). We conclude that in experienced BHD there is a transient alteration in lung elastic recoil. Resting lung function did not reveal a pattern indicative of altered lung ventilatory or muscle function.