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Factors that are potentially important in the pulmonary pathogenesis of asbestos and other mineral particles are: 1) morphology, 2) Fe-content, 3) solubility under intraphagosomal conditions, 4) value and sign of the surface potential of the particle, 5) hydrophobicity or hydrophilicity, 6) capacity to activate phagocytic leukocytes, and 7) duration of exposure to the particles. The order of importance of these factors in causing severe or fatal pulmonary pathogenicity is estimated to be: 1 > 3 > 7 > 6 ≫ 5 > 4 > 2. The order of pathogenicity of the minerals is estimated as: amphibole asbestos: crocidolite, tremolite, amosite > erionite > serpentine asbestos: chrysotile > talc > silica > simple metal oxides. Particle length, duration of exposure to the particles, and pre-treatment of the particles may however enhance the pathogenic potential of any of the lower-ranked particles.
In a well-known passage (Juv. 13 (7).473a15–474a24), Aristotle preserves a fragment of Empedocles’ poem dealing with respiration, in which the clepsydra is used as a model for breathing. Although there is a substantial literature on this subject, most scholars have focused on explaining Empedocles’ account of the mode of operation of the clepsydra as well as on assessing the extent to which Aristotle’s interpretation does justice to Empedocles’ fragment. What has received little attention is the fact that Aristotle begins his criticism of Empedocles by offering a specific counterproposal of his own, one that rests on the idea that the mechanism of respiration can be explained in a much clearer fashion through the analogy of a forge bellows. References to bellows are actually already traceable to Homer. At the same time, the bellows–lungs analogy continued to be used for centuries after Aristotle. The aim of this chapter is to provide an overview of the existing literary and archaeological evidence about bellows in Greek antiquity in order to build a complete picture of its function and hence clarify Aristotle’s theory of respiration.
Dromedary camel (Camelus dromedarius) is adapted to survive the harsh environments. It has some key adaptation peculiarities in various organs. In this study, we aimed to map the distribution pattern of unique regulatory devices along the course of the pulmonary vessels using histological and histochemical analyses. Arteries with variable wall thickness and spirally oriented course were recorded within the adventitia of the main pulmonary artery. Throttle arteries and glomus bolsters were found within the wall of the lobar pulmonary artery. The bronchial artery was located within the wall of all bronchi reaching the subsegmental branches and it had elastic longitudinal muscular intima bolsters. Arteries with double muscular media were demonstrated in the pulmonary pleura. These bolsters are suggested to play a complicated role that allows for hemodynamic, humeral, and thermoregulatory activities. The lumen of some subsegmental pulmonary veins revealed occasional constrictions arising from the corresponding muscular pad-like protrusions of the tunica media. These veins may possess occlusive or constrictive mechanisms and their obstruction induces engorgement of the associated capillary bed in addition to restricting venous outflow. Collectively, these data strongly recommend a crucial role for the special regulatory devices in preserving the camel pulmonary function in the harsh desert environment.
Ascaris lumbricoides and Ascaris suum are helminth parasites of humans and pigs, respectively. The life cycle of Ascaris sets it apart from the other soil-transmitted helminths because of its hepato-tracheal migration. Larval migration contributes to underestimated morbidity in humans and pigs. This migration, coupled with a lack of a murine model in which the Ascaris parasite might complete its life cycle, has undoubtedly contributed to the neglected status of the ascarid. Our knowledge of the epidemiology of adult worm infections had led us to an enhanced understanding of patterns of infection such as aggregation and predisposition; however, the mechanisms underlying these complex phenomena remain elusive. Carefully controlled experiments in defined inbred strains of mice – with enhanced recovery of larvae in tandem with measurements of cellular, histopathological and molecular processes – have greatly enhanced our knowledge of the early phase of infection, a phase crucial to the success or failure of adult worm establishment. Furthermore, the recent development of a mouse model of susceptibility and resistance, with highly consistent and diverging Ascaris larval burdens in the murine lungs, represents the extremes of the host phenotype displayed in the aggregated distribution of worms and provides an opportunity to explore the mechanistic basis that confers predisposition to light and heavy Ascaris infection. Certainly, detailed knowledge of the cellular hepatic and pulmonary responses at the molecular level can be accrued from murine models of infection and, once available, may enhance our ability to develop immunomodulatory therapies to elicit resistance to infection.
Although abundant evidence exists that adverse events during pregnancy lead to chronic conditions, there is limited information on the impact of acute insults such as sepsis. This study tested the hypothesis that impaired fetal development leads to altered organ responses to a septic insult in both male and female adult offspring. Fetal growth restricted (FGR) rats were generated using a maternal protein-restricted diet. Male and female FGR and control diet rats were housed until 150–160 d of age when they were exposed either a saline (control) or a fecal slurry intraperitoneal (Sepsis) injection. After 6 h, livers and lungs were analyzed for inflammation and, additionally, the amounts and function of pulmonary surfactant were measured. The results showed increases in the steady-state mRNA levels of inflammatory cytokines in the liver in response to the septic insult in both males and females; these responses were not different between FGR and control diet groups. In the lungs, cytokines were not detectable in any of the experimental groups. A significant decrease in the relative amount of surfactant was observed in male FGR offspring, but this was not observed in control males or in female animals. Overall, it is concluded that FGR induced by maternal protein restriction does not impact liver and lung inflammatory response to sepsis in either male or female adult rats. An altered septic response in male FGR offspring with respect to surfactant may imply a contribution to lung dysfunction.
The main objective was to study different clinical presentations and outcomes of patients after acute industrial chlorine gas exposure in Oman with evaluation of overall incident management to help develop a chemical exposure incident protocol.
Methods:
This was a retrospective observational study of 15 patients exposed to chlorine gas after an accidental chlorine gas leak in a metal melting factory in Oman.
Results:
Six (40%) patients were admitted and nine (60%) patients were discharged from the emergency department (ED) after initial management. The important post-chlorine gas exposure clinical symptoms were eye irritation (66.6%), cough (73.3%), shortness of breath (40.0%), chest discomfort (66.6%), rhinorrhea (66.6%), dizziness (40.0%), vomiting (46.6%), sore throat (13.3%), and stridor (53.3%). Important signs included tachycardia (40.0%), tachypnea (40.0%), wheeze (20.0%), and use of accessory muscles for breathing (20.0%). Signs and symptoms of eye irritation, rhinorrhea, tachycardia, tachypnea, wheeze, and use of accessory muscles for breathing have shown significant correlation with outcome (admission) having P value of <.05.
Conclusion:
In the presented acute chlorine gas exposure incidence, 15 exposed persons were brought to the ED, out of which six were admitted and nine were discharged after symptomatic treatment. Signs and symptoms of eye irritation, rhinorrhea, tachycardia, tachypnea, wheeze, and use of accessory muscles of breathing show significant relation with the outcome of admission.
Chest CT evaluation is often vital to determine patients suspected of COVID-19 pneumonia. The aim of this study was to determine the evolution of lung abnormalities evaluated by quantitative CT techniques in patients with COVID-19 infection from initial diagnosis to recovery. This retrospective study included 16 patients with COVID-19 infection from 30 January 2020 through 11 March 2020. Repeat chest CT examinations were obtained for three or more scans per patient. We measured total volume and mean CT value of lung lesions in each patient per scan, and then calculated the mass, which equals to volume × (CT value + 1000). Dynamic evolution of chest CT imaging as a function of time was fitted by non-linear regression model in terms of mass, volume and CT value, respectively. According to the fitting curves, we redefined the evolution of lung abnormalities: progressive stage (0–5 days), infection emerged and rapidly aggravated; peak stage (5–15 days), the greatest severity at approximate 7–8 days after onset; and absorption stage (15–30 days), the lesions slowly and gradually resolved.
Lung tumours, especially those in the lower lobes, can move a lot during respiration; this motion needs to be accounted for during radiotherapy. In cases where 4D CT simulation scans are not performed, the current protocol at our centre is to apply a generic (internal motion + setup) margin of 0·70 cm in the axial plane and 1·20 cm in the longitudinal plane to all lung tumours, regardless of location. We analyse the tumour motions of a cohort of our local patients and categorise them into different locations in the lung. We seek to assess the adequacy of the current margins and to derive a more accurate set of standard margins which are specific for lung tumour locations.
Methods:
All cases of lung tumours treated with stereotactic ablative radiotherapy between 2012 and 2016 were identified retrospectively and 4D CT scan data analysed. These tumours were grouped into the following locations: upper zone (UZ), middle zone (MZ) and lower zone (LZ). The treatment planning system was used to generate the displacements of the centre of mass of the tumours in the right–left, anterior–posterior and superior–inferior axes; these were compared with the current generic margins. Median displacements were calculated for each axis in each location. New planning target volume (PTV) margins were derived by summing the median displacement, median absolute deviation (MAD) and 0·5 cm (for setup error).
Results:
Sixty-three cases were eligible for analyses. Motion in the superior–inferior direction was the greatest for all tumour locations, ranging from a median of 0·17 cm (MAD 0·12 cm) in UZ to 0·77 cm (MAD 0·27 cm) in LZ. Median tumour displacements in the anterior–posterior and right–left axes were similar for all locations, <0·30 and 0·20 cm, respectively. The current generic margins were adequate for only one-third of the cases in this study. A new PTV margin of 2·10 cm in the superior–inferior axis may be required for LZ tumours, while an additional 1–2 mm should be added to the current radial margins.
Conclusion:
The current generic margins are inadequate for the majority of cases. Tumour motion is the greatest in LZ in the superior–inferior axis. Motion mitigation strategies are essential for large LZ tumours.
Lung ultrasound has value in diagnosing dyspnea. The main objective of this study was to evaluate the accuracy of a modified lung ultrasound (MLUS) score to predict the severity of acute dyspnea in elderly patients.
Methods
This was an observational single-centre study including patients over age 64 admitted to the emergency department for acute dyspnea with hypoxia. Participants had an early lung ultrasound performed by a dedicated emergency physician, followed by the usual care by a team blinded to the lung ultrasound results. Patients were allocated by disposition to either a critical care (CC) group (patients who needed admission to the intensive care unit [ICU] and/or who died within 48 h) or a standard care group.
Results
Among 137 patients analysed (mean age 79 ± 13 years, 74 [54%] women), 43 (31%) were categorized into the CC group. The time taken to obtain the MLUS was 30 ± 22 min. The area under the receiver operating characteristic curve of the MLUS for predicting the CC group was 0.97 (0.92–0.99; p < 0.01) with a cut-off set strictly above 17 for 93% sensitivity (81–99), 99% specificity (94–100), a positive predictive value of 98% (87–100), a negative predictive value of 97% (91–99), a positive likelihood ratio of 86, a negative likelihood ratio of 0.07, and a diagnostic accuracy of 97% (93–99). In a multivariate analysis, the MLUS was the only independent associated factor for the CC group.
Conclusion
An early lung ultrasound score can predict the need for ICU admission and/or death within 48 hours in elderly dyspneic patients.
Elevated levels of organochlorines (OC) have been reported in Inuit populations in the Arctic. We hypothesized that prenatal exposure to a Canadian Arctic OC mixture adversely affects male reproductive function and health with age. Sprague–Dawley female rats (F0) were gavaged with an environmentally relevant concentration of an Arctic OC mixture or corn oil (Control) during mating with untreated males until parturition (F1 litters). After postnatal day (PND) 90, the weights of the OC F1 males differed dramatically relative to Controls (P<0.05; n=10) and they exhibited respiratory distress. Except for possible thinning of the alveolar barrier, histological observation of the lungs revealed no apparent pathology to explain the respiratory distress. At PND 365, OC F1 males had reduced relative reproductive organ weights and lower sperm quality than Controls (P<0.05). At PND 90, OC F1 males were subfertile (P<0.05), but were infertile at PND 365. In conclusion, environmentally relevant prenatal OC exposure reduced reproductive function and health in aging male rats, providing new insight into the effects of early-life exposures to these contaminants.
This review details a selection of occupational lung diseases, particularly fibrosis (scarring) and tumours that can arise following exposure to mineral dusts. Also described are the sequential repair processes of the lung including oedema, inflammation, epithelial changes and finally scarring. The features by which a dust can be considered bioreactive including shape, size, surface area, durability and surface chemistry is discussed together with the importance of the mass deposited in the lung and particle clearance, particularly through lymphatic drainage. Emphasis is given to the importance of surface chemistry in that crystalline minerals, especially silicas, are often highly bioreactive whereas amorphous silicas or crystalline forms that have aged in the laboratory have lesser activity. Nevertheless, all forms of crystalline silica are particularly hazardous with the long-term ability to produce irreversible disease (fibrosis) when administered to experimental animals.
Heterogeneity in pulmonary microvascular blood flow (perfusion) provides an early indicator of lung disease or disease susceptibility. However, most computational models of the pulmonary vasculature neglect structural heterogeneities, and are thus not accurate predictors of lung function in disease that is not diffuse (spread evenly through the lung). Models that do incorporate structural heterogeneity have either neglected the temporal dynamics of blood flow, or the structure of the smallest blood vessels. Larger than normal oscillations in pulmonary capillary calibre, high oscillatory stress contribute to disease progression. Hence, a model that captures both spatial and temporal heterogeneity in pulmonary perfusion could provide new insights into the early stages of pulmonary vascular disease. Here, we present a model of the pulmonary vasculature, which captures both flow dynamics, and the anatomic structure of the pulmonary blood vessels from the right to left heart including the micro-vasculature. The model is compared to experimental data in normal lungs. We confirm that spatial heterogeneity in pulmonary perfusion is time-dependent, and predict key features of pulmonary hypertensive disease using a simple implementation of increased vascular stiffness.
Deep inspiration breath hold (DIBH) is a method of motion management used in stereotactic ablative body radiotherapy (SABR) for lung tumours. An external gating block marker can be used as a tumour motion surrogate, however, inter-fraction gross target volume (GTV) displacement within DIBH occurs. This study measured this displacement during a reproducible breath hold regime. In addition, factors such as position of the gating block marker were analysed.
Methods and materials
A total of 121 cone beam computed tomography scans (CBCTs) from 22 patients who received DIBH SABR were retrospectively evaluated and the magnitude of inter-fraction GTV displacement was calculated for each fraction. This data was analysed to assess if any correlation existed between tumour displacement and variation in the gating block marker position on the patient, the amplitude of breath hold (BH) at computed tomography (CT), the amplitude of BH at treatment and the tumour location.
The measured tumour displacement was applied to the original planning CT to evaluate the dosimetric effect on surrounding organs at risk (OARs) using cumulative dose volume histograms (DVHs).
Results
BH amplitude was reproducible within 0·13±0·1 cm (mean±standard deviation). The magnitude of tumour displacement within BH ranged from 0 to 1·52 cm (0·41±0·28 cm). Displacement in the superior-inferior, anterior-posterior and left-right planes were 0·31±0·26 cm, 0·16±0·18 cm and 0·07±0·12 cm, respectively. No statistically significant correlation was detected between tumour displacement within DIBH and the factors investigated. The range of variation in OAR dose was −7·0 to +3·6 Gy with one statistically significant increase in OAR dose observed (oesophagus mean dose increasing by 0·16 Gy).
Findings
Reproducible BH was achievable across a range of patients. Inter-fraction GTV displacement measured 0·41±0·28 cm. Due to this low level of motion, the correction of soft tissue moves did not adversely affect OAR dose.
Asbestos bodies are the histological hallmarks of asbestos exposure. Both conventional and advanced techniques are used to evaluate abundance and composition in histological samples. We previously reported the possibility of using synchrotron X-ray fluorescence microscopy (XFM) for analyzing the chemical composition of asbestos bodies directly in lung tissue samples. Here we applied a high-performance synchrotron X-ray fluorescence (XRF) set-up that could allow new protocols for fast monitoring of the occurrence of asbestos bodies in large histological sections, improving investigation of the related chemical changes. A combination of synchrotron X-ray transmission and fluorescence microscopy techniques at different energies at three distinct synchrotrons was used to characterize asbestos in paraffinated lung tissues. The fast chemical imaging of the XFM beamline (Australian Synchrotron) demonstrates that asbestos bodies can be rapidly and efficiently identified as co-localization of high calcium and iron, the most abundant elements of these formations inside tissues (Fe up to 10% w/w; Ca up to 1%). By following iron presence, we were also able to hint at small asbestos fibers in pleural spaces. XRF at lower energy and at higher spatial resolution was afterwards performed to better define small fibers. These analyses may predispose for future protocols to be set with laboratory instruments.
Calypso® 4D Localization System is a system based on electromagnetic transponders detection enabling precise 3D localisation and continuous tracking of tumour target. This review intended to provide information in order to (1) show how Calypso® 4D Localization System works, (2) to present advantages and disadvantages of this system, (3) to gather information from several clinical studies and, finally, (4) to refer Calypso® System as a tool in dynamic multileaf collimator studies for target motion compensation.
Methods
A structured search was carried out on B-On platform. The key words used in this research were ‘Calypso’, ‘Transponder’, ‘Electromagnetic Localization’, ‘Electromagnetic Tracking’, ‘Target Localization’, ‘Intrafraction Motion’ and ‘DMLC’.
Review
Treatment the implanted transponders are excited by an electromagnetic field and resonate back. These frequencies are detected and Calypso® software calculates the position of the transponders. If the movement detected is larger than the limits previously defined, irradiation can be stopped. The system has been proven to be submillimetre accurate.
Discussion
Calypso® System has been presented as an accurate tool in prostate radiotherapy treatments. The application of this system to other clinical sites is being developed.
Conclusion
The Calypso® System allows real-time localisation and monitoring of the target, without additional ionising radiation administration. It has been a very useful tool in prostate cancer treatment.
This chapter discusses the diagnosis, evaluation and management of acute respiratory distress syndrome (ARDS). Pulmonary edema in ARDS is heterogeneous and leads to atelectatic or consolidated areas of lung interspersed with relatively unaffected regions, creating areas of intrapulmonary shunt, which results in hypoxemia that does not improve with oxygen administration alone. As pulmonary edema accumulates in the initial exudative phase of the disease, patients become dyspneic and demonstrate increased work of breathing. Due to worsening lung compliance, tidal volumes decrease and respiratory rate increases. Patients become progressively hypoxemic due to both worsening V/Q mismatch and shunt physiology. The respiratory failure is not fully explained by cardiac failure or volume overload. If a known risk factor for ARDS is not present, objective assessment such as echocardiography should be obtained to rule out hydrostatic edema. On a chest radiograph, ARDS looks essentially the same as cardiogenic pulmonary edema.
Correlations between host phenotype and vulnerability to parasites can clarify the processes that enhance rates of parasitism, and the effects of parasites on their hosts. We studied an invasive parasite (the pentastome Raillietiella frenatus, subclass Pentastomida, order Cephalobaenida) infecting a new host (the invasive cane toad Rhinella marina), in tropical Australia. We dissected toads over a 27-month period to investigate seasonal changes in pentastome population dynamics and establish which aspects of host phenotype are related to infection. Pentastome prevalence and intensity varied seasonally; male toads were 4 times more likely to be infected than were females; and prevalence was highest in hosts of intermediate body size. The strong sex effect may reflect habitat or dietary divergence between the sexes, resulting in males encountering parasites more often. The relationship between pentastome prevalence and host size likely reflects a role for acquired immunity in preventing re-infection. Infection did not influence host body condition (fatbody size), suggesting that R. frenatus does not impose high energy costs in cane toads. Infected toads had heavier spleens (likely an immune response to infection) and larger testes (perhaps since reproductively active hosts have altered microhabitat use and/or immunocompetence) than did uninfected conspecifics. Although experimental studies are required to identify the causal bases of such patterns, our data confirm that infection status within a population can be strongly linked to host phenotypic traits.
Quantitative and/or qualitative analysis of exhaled carbon dioxide (CO2) has become standard practice in many clinical situations. The rationale for measuring the partial pressure of CO2 (PCO2) in exhaled gas is the assumption that end-tidal PCO2 (PETCO2) is a reflection of alveolar PCO2 (PaCO2). Hemoglobin plays an essential role in CO2 transport and elimination. Elimination of CO2 from the lung occurs as a function of gas exchange between the atmosphere and alveoli. In order to gain a greater understanding of the gradient between PaCO2 and PETCO2, an analysis of the interaction of pulmonary ventilation and perfusion is necessary. The alveolar gas equation (AGE) is used to analyze the effect of ventilation on oxygenation of arterial blood. An understanding of the interrelationship between pulmonary perfusion, ventilation, tidal volume, and regional VA/Q will enhance the utility of capnography as a monitor.