84 resultados para respiratory muscles


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Dry Powder Inhaler (DPI) technology has a significant impact in the treatment of various respiratory disorders. DPI formulations consist of a micronized drug (<5ìm) blended with an inert coarse carrier, for which lactose is widely used to date. DPIs are one of the inhalation devices which are used to target the delivery of drugs to the lungs. Drug delivery via DPI formulations is influenced by the physico-chemical characteristics of lactose particles such as size, shape, surface roughness and adhesional forces. Commercially available DPI formulations, which utilise lactose as the carrier, are not efficient in delivering drug to the lungs. The reasons for this are the surface morphology, adhesional properties and surface roughness of lactose. Despite several attempts to modify lactose, the maximum efficient drug delivery to the lungs remains limited; hence, exploring suitable alternative carriers for DPIs is of paramount importance. Therefore, the objective of the project was to study the performance of spherical polymer microparticles as drug carriers and the factors controlling their performance. This study aimed to use biodegradable polymer microspheres as alternative carriers to lactose in DPIs for achieving efficient drug delivery into the lungs. This project focused on fabricating biodegradable polymer microparticles with reproducible surface morphology and particle shape. The surface characteristics of polymeric carriers and the adhesional forces between the drug and carrier particles were investigated in order to gain a better understanding of their influence on drug dispersion. For this purpose, two biodegradable polymers- polycaprolactone (PCL) and poly (DL-lactide-co-glycolide) (PLGA) were used as the carriers to deliver the anti-asthmatic drug - Salbutamol Sulphate (SS). The first study conducted for this dissertation was the aerosolization of SS from mixtures of SS and PCL or PLGA microparticles. The microparticles were fabricated using an emulsion technique and were characterized by laser diffraction for particle size analysis, Scanning Electron Microscopy (SEM) for surface morphology and X-ray Photoelectron Spectroscopy (XPS) to obtain surface elemental composition. The dispersion of the drug from the DPI formulations was determined by using a Twin Stage Impinger (TSI). The Fine particle Fraction (FPF) of SS from powder mixtures was analyzed by High Performance Liquid Chromatography (HPLC). It was found that the drug did not detach from the surface of PCL microspheres. To overcome this, the microspheres were coated with anti-adherent agents such as magnesium stearate and leucine to improve the dispersion of the drug from the carrier surfaces. It was found that coating the PCL microspheres helped in significantly improving the FPF of SS from the PCL surface. These results were in contrast to the PLGA microspheres which readily allowed detachment of the SS from their surface. However, coating PLGA microspheres with antiadherent agents did not further improve the detachment of the drug from the surface. Thus, the first part of the study demonstrated that the surface-coated PCL microspheres and PLGA microspheres can be potential alternatives to lactose as carriers in DPI formulations; however, there was no significant improvement in the FPF of the drug. The second part of the research studied the influence of the size of the microspheres on the FPF of the drug. For this purpose, four different sizes (25 ìm, 48 ìm, 100 ìm and 150 ìm) of the PCL and PLGA microspheres were fabricated and characterized. The dispersion of the drug from microspheres of different sizes was determined. It was found that as the size of the carrier increased there was a significant increase in the FPF of SS. This study suggested that the size of the carrier plays an important role in the dispersion of the drug from the carrier surface. Subsequent experiments in the third part of the dissertation studied the surface properties of the polymeric carrier. The adhesion forces existing between the drug particle and the polymer surfaces, and the surface roughness of the carriers were quantified using Atomic Force Microscopy (AFM). A direct correlation between adhesion forces and dispersion of the drug from the carrier surface was observed suggesting that adhesion forces play an important role in determining the detachment potential of the drug from the carrier surface. However, no direct relationship between the surface roughness of the PCL or PLGA carrier and the FPF of the drug was observed. In conclusion, the body of work presented in this dissertation demonstrated the potential of coated PCL microspheres and PLGA microspheres to be used in DPI formulations as an alternative carrier to sugar based carriers. The study also emphasized the role of the size of the carrier particles and the forces of interaction prevailing between the drug and the carrier particle surface on the aerosolization performances of the drug.

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Particulate matter (PM) emissions involve a complex mixture of solid and liquid particles suspended in a gas, where it is noted that PM emissions from diesel engines are a major contributor to the ambient air pollution problem. Whilst epidemiological studies have shown a link between increased ambient PM emissions and respiratory morbidity and mortality, studies of this design are not able to identify the PM constituents responsible for driving adverse respiratory health effects. This review explores in detail the physico-chemical properties of diesel particulate matter (DPM), and identifies the constituents of this pollution source that are responsible for the development of respiratory disease. In particular, this review shows that the DPM surface area and adsorbed organic compounds play a significant role in manifesting chemical and cellular processes that if sustained can lead to the development of adverse respiratory health effects. The mechanisms of injury involved included: inflammation, innate and acquired immunity, and oxidative stress. Understanding the mechanisms of lung injury from DPM will enhance efforts to protect at-risk individuals from the harmful respiratory effects of air pollutants.

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Background: Antibiotics misuse is currently one of the major public health issues worldwide. This misuse can lead to the development of bacterial resistance, increasing the burden of chronic diseases, rising costs of health services, and the development of side effects. Several factors may influence this pattern of overuse. Objectives:This article will review the pertinent factors contributing to the overuse of antibiotics worldwide, and to assess the intervention strategies to limit this overuse. Methods: studies about antibiotics use in children were reviewed from several electronic databases, such as MEDLINE and Pubmed. Results: Factors contributing to the overuse of antibiotics could include psychosocial factors, such as behaviors and attitudes (e.g. self-medication, over-the-counter medication, or patients/parents pressure), and demographic factors, such as socio-economic status and education level. Several intervention strategies were reported to be effective in reducing the overuse of antibiotics, such as health education, doctor-patient communication, and policies change. Multifaceted interventions were found to be the most effective in reducing the antibiotics overuse.

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17.1 Drugs for bronchial asthma and Chronic Obstructive Pulmonary Disease (COPD) 17.1.1 Introduction to asthma 17.1.2 Introduction to COPD 17.1.3 Drug delivery by inhalation 17.1.4 Drugs to treat 17.1.4.1 β2-adrenoceptor agonists 17.1.4.2 Muscarinic receptor antagonists 17.1.4.3 Leukotriene receptor antagonists 17.1.4.4 Theophylline 17.1.4.5 Oxygen for COPD 17.1.5 Drugs to prevent asthma 31.5.1 Glucocorticoids 31.5.2 Cromolyn sodium 17.1.6 Combination to treat and prevent asthma 17.1.7 Drug for allergic asthma – omalizumab 17.1.8 Emergency treatment of asthma 17.2. Expectorants, mucolytics, cough and oxygen 17.2.1 Introduction to expectorants and mucolytics 17.2.2 Expectorants 17.2.3 Mucolytics 17.2.4 Cough 17.2.5 Oxygen 17.3. Drugs for rhinitis and rhinorrea 17.3.1 Introduction 17.3.2 Histamine and H1-receptor antagonists 17.3.3 Sympathomimetic 17.3.4 Muscarinic receptor antagonists 17.3.4 Cromolyn sodium 17.3.5 Glucocorticoids

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Critically ill patients receiving extracorporeal membrane oxygenation (ECMO) are often noted to have increased sedation requirements. However, data related to sedation in this complex group of patients is limited. The aim of our study was to characterise the sedation requirements in adult patients receiving ECMO for cardiorespiratory failure. A retrospective chart review was performed to collect sedation data for 30 consecutive patients who received venovenous or venoarterial ECMO between April 2009 and March 2011. To test for a difference in doses over time we used a regression model. The dose of midazolam received on ECMO support increased by an average of 18 mg per day (95% confidence interval 8, 29 mg, P=0.001), while the dose of morphine increased by 29 mg per day (95% confidence interval 4, 53 mg, P=0.021) The venovenous group received a daily midazolam dose that was 157 mg higher than the venoarterial group (95% confidence interval 53, 261 mg, P=0.005). We did not observe any significant increase in fentanyl doses over time (95% confidence interval 1269, 4337 µg, P=0.94). There is a significant increase in dose requirement for morphine and midazolam during ECMO. Patients on venovenous ECMO received higher sedative doses as compared to patients on venoarterial ECMO. Future research should focus on mechanisms behind these changes and also identify drugs that are most suitable for sedation during ECMO.

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Background: Bicycle commuting in an urban environment of high air pollution is known as a potential health risk, especially for susceptible individuals. While risk management strategies aimed to reduce motorised traffic emissions exposure have been suggested, limited studies have assessed the utility of such strategies in real-world circumstances. Objectives: The potential of reducing exposure to ultrafine particles (UFP; < 0.1 µm) during bicycle commuting by lowering interaction with motorised traffic was investigated with real-time air pollution and acute inflammatory measurements in healthy individuals using their typical, and an alternative to their typical, bicycle commute route. Methods: Thirty-five healthy adults (mean ± SD: age = 39 ± 11 yr; 29% female) each completed two return trips of their typical route (HIGH) and a pre-determined altered route of lower interaction with motorised traffic (LOW; determined by the proportion of on-road cycle paths). Particle number concentration (PNC) and diameter (PD) were monitored in real-time in-commute. Acute inflammatory indices of respiratory symptom incidence, lung function and spontaneous sputum (for inflammatory cell analyses) were collected immediately pre-commute, and one and three hours post-commute. Results: LOW resulted in a significant reduction in mean PNC (1.91 x e4 ± 0.93 x e4 ppcc vs. 2.95 x e4 ± 1.50 x e4 ppcc; p ≤ 0.001). Besides incidence of in-commute offensive odour detection (42 vs. 56 %; p = 0.019), incidence of dust and soot observation (33 vs. 47 %; p = 0.038) and nasopharyngeal irritation (31 vs. 41 %; p = 0.007), acute inflammatory indices were not significantly associated to in-commute PNC, nor were these indices reduced with LOW compared to HIGH. Conclusions: Exposure to PNC, and the incidence of offensive odour and nasopharyngeal irritation, can be significantly reduced when utilising a strategy of lowering interaction with motorised traffic whilst bicycle commuting, which may bring important benefits for both healthy and susceptible individuals.

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Intense exercise stimulates the systemic release of a variety of factors that alter neutrophil surface receptor expression and functional activity. These alterations may influence resistance to infection after intense exercise. The aim of this study was to examine the influence of exercise intensity on neutrophil receptor expression, degranulation (measured by plasma and intracellular myeloperoxidase concentrations), and respiratory burst activity. Ten well-trained male runners ran on a treadmill for 60 min at 60% [moderate-intensity exercise (MI)] and 85% maximal oxygen consumption [high-intensity exercise (HI)]. Blood was drawn immediately before and after exercise and at 1 h postexercise. Immediately after HI, the expression of the neutrophil receptor CD16 was significantly below preexercise values (P < 0.01), whereas MI significantly reduced CD35 expression below preexercise values (P < 0.05). One hour after exercise at both intensities, there was a significant decline in CD11b expression (P < 0.05) and a further decrease in CD16 expression compared with preexercise values (P < 0.01). CD16 expression was lower 1 h after HI than 1 h after MI (P < 0.01). Immediately after HI, intracellular myeloperoxidase concentration was less than preexercise values (P < 0.01), whereas plasma myeloperoxidase concentration was greater (P < 0.01), indicating that HI stimulated neutrophil degranulation. Plasma myeloperoxidase concentration was higher immediately after HI than after MI (P < 0.01). Neutrophil respiratory burst activity increased after HI (P < 0.01). In summary, both MI and HI reduced neutrophil surface receptor expression. Although CD16 expression was reduced to a greater extent after HI, this reduction did not impair neutrophil degranulation and respiratory burst activity.

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Neutrophils constitute 50-60% of all circulating leukocytes; they present the first line of microbicidal defense and are involved in inflammatory responses. To examine immunocompetence in athletes, numerous studies have investigated the effects of exercise on the number of circulating neutrophils and their response to stimulation by chemotactic stimuli and activating factors. Exercise causes a biphasic increase in the number of neutrophils in the blood, arising from increases in catecholamine and cortisol concentrations. Moderate intensity exercise may enhance neutrophil respiratory burst activity, possibly through increases in the concentrations of growth hormone and the inflammatory cytokine IL-6. In contrast, intense or long duration exercise may suppress neutrophil degranulation and the production of reactive oxidants via elevated circulating concentrations of epinephrine (adrenaline) and cortisol. There is evidence of neutrophil degranulation and activation of the respiratory burst following exercise-induced muscle damage. In principle, improved responsiveness of neutrophils to stimulation following exercise of moderate intensity could mean that individuals participating in moderate exercise may have improved resistance to infection. Conversely, competitive athletes undertaking regular intense exercise may be at greater risk of contracting illness. However, there are limited data to support this concept. To elucidate the cellular mechanisms involved in the neutrophil responses to exercise, researchers have examined changes in the expression of cell membrane receptors, the production and release of reactive oxidants and more recently, calcium signaling. The investigation of possible modifications of other signal transduction events following exercise has not been possible because of current methodological limitations. At present, variation in exercise-induced alterations in neutrophil function appears to be due to differences in exercise protocols, training status, sampling points and laboratory assay techniques.

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Background Surveillance programs and research for acute respiratory infections in remote Australian communities are complicated by difficulties in the storage and transport of frozen samples to urban laboratories for testing. This study assessed the sensitivity of a simple method for transporting nasal swabs from a remote setting for bacterial polymerase chain reaction (PCR) testing. Methods We sampled every individual who presented to a remote community clinic over a three week period in August at a time of low influenza and no respiratory syncytial virus activity. Two anterior nasal swabs were collected from each participant. The left nare specimen was mailed to the laboratory via routine postal services. The right nare specimen was transported frozen. Testing for six bacterial species was undertaken using real-time PCR. Results One hundred and forty participants were enrolled who contributed 150 study visits and paired specimens for testing. Respiratory illnesses accounted for 10% of the reasons for presentation. Bacteria were identified in 117 (78%) presentations for 110 (79.4%) individuals; Streptococcus pneumoniae and Haemophilus influenzae were the most common (each identified in 58% of episodes). The overall sensitivity for any bacterium detected in mailed specimens was 82.2% (95% CI 73.6, 88.1) compared to 94.8% (95% CI 89.4, 98.1) for frozen specimens. The sensitivity of the two methods varied by species identified. Conclusion The mailing of unfrozen nasal specimens from remote communities appears to influence the utility of the specimen for bacterial studies, with a loss in sensitivity for the detection of any species overall. Further studies are needed to confirm our finding and to investigate the possible mechanisms of effect. Clinical trial registration Australia and New Zealand Clinical Trials Registry Number: ACTRN12609001006235. Keywords: Respiratory bacteria; RT-PCR; Specimen transport; Laboratory methods

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Bicycle commuting has the potential to be an effective contributing solution to address some of modern society’s biggest issues, including cardiovascular disease, anthropogenic climate change and urban traffic congestion. However, individuals shifting from a passive to an active commute mode may be increasing their potential for air pollution exposure and the associated health risk. This project, consisting of three studies, was designed to investigate the health effects of bicycle commuters in relation to air pollution exposure, in a major city in Australia (Brisbane). The aims of the three studies were to: 1) examine the relationship of in-commute air pollution exposure perception, symptoms and risk management; 2) assess the efficacy of commute re-routing as a risk management strategy by determining the exposure potential profile of ultrafine particles along commute route alternatives of low and high proximity to motorised traffic; and, 3) evaluate the feasibility of implementing commute re-routing as a risk management strategy by monitoring ultrafine particle exposure and consequential physiological response from using commute route alternatives based on real-world circumstances; 3) investigate the potential of reducing exposure to ultrafine particles (UFP; < 0.1 µm) during bicycle commuting by lowering proximity to motorised traffic with real-time air pollution and acute inflammatory measurements in healthy individuals using their typical, and an alternative to their typical, bicycle commute route. The methods of the three studies included: 1) a questionnaire-based investigation with regular bicycle commuters in Brisbane, Australia. Participants (n = 153; age = 41 ± 11 yr; 28% female) reported the characteristics of their typical bicycle commute, along with exposure perception and acute respiratory symptoms, and amenability for using a respirator or re-routing their commute as risk management strategies; 2) inhaled particle counts measured along popular pre-identified bicycle commute route alterations of low (LOW) and high (HIGH) motorised traffic to the same inner-city destination at peak commute traffic times. During commute, real-time particle number concentration (PNC; mostly in the UFP range) and particle diameter (PD), heart and respiratory rate, geographical location, and meteorological variables were measured. To determine inhaled particle counts, ventilation rate was calculated from heart-rate-ventilation associations, produced from periodic exercise testing; 3) thirty-five healthy adults (mean ± SD: age = 39 ± 11 yr; 29% female) completed two return trips of their typical route (HIGH) and a pre-determined altered route of lower proximity to motorised traffic (LOW; determined by the proportion of on-road cycle paths). Particle number concentration (PNC) and diameter (PD) were monitored in real-time in-commute. Acute inflammatory indices of respiratory symptom incidence, lung function and spontaneous sputum (for inflammatory cell analyses) were collected immediately pre-commute, and one and three hours post-commute. The main results of the three studies are that: 1) healthy individuals reported a higher incidence of specific acute respiratory symptoms in- and post- (compared to pre-) commute (p < 0.05). The incidence of specific acute respiratory symptoms was significantly higher for participants with respiratory disorder history compared to healthy participants (p < 0.05). The incidence of in-commute offensive odour detection, and the perception of in-commute air pollution exposure, was significantly lower for participants with smoking history compared to healthy participants (p < 0.05). Females reported significantly higher incidence of in-commute air pollution exposure perception and other specific acute respiratory symptoms, and were more amenable to commute re-routing, compared to males (p < 0.05). Healthy individuals have indicated a higher incidence of acute respiratory symptoms in- and post- (compared to pre-) bicycle commuting, with female gender and respiratory disorder history indicating a comparably-higher susceptibility; 2) total mean PNC of LOW (compared to HIGH) was reduced (1.56 x e4 ± 0.38 x e4 versus 3.06 x e4 ± 0.53 x e4 ppcc; p = 0.012). Total estimated ventilation rate did not vary significantly between LOW and HIGH (43 ± 5 versus 46 ± 9 L•min; p = 0.136); however, due to total mean PNC, accumulated inhaled particle counts were 48% lower in LOW, compared to HIGH (7.6 x e8 ± 1.5 x e8 versus 14.6 x e8 ± 1.8 x e8; p = 0.003); 3) LOW resulted in a significant reduction in mean PNC (1.91 x e4 ± 0.93 x e4 ppcc vs. 2.95 x e4 ± 1.50 x e4 ppcc; p ≤ 0.001). Commute distance and duration were not significantly different between LOW and HIGH (12.8 ± 7.1 vs. 12.0 ± 6.9 km and 44 ± 17 vs. 42 ± 17 mins, respectively). Besides incidence of in-commute offensive odour detection (42 vs. 56 %; p = 0.019), incidence of dust and soot observation (33 vs. 47 %; p = 0.038) and nasopharyngeal irritation (31 vs. 41 %; p = 0.007), acute inflammatory indices were not significantly associated to in-commute PNC, nor were these indices reduced with LOW compared to HIGH. The main conclusions of the three studies are that: 1) the perception of air pollution exposure levels and the amenability to adopt exposure risk management strategies where applicable will aid the general population in shifting from passive, motorised transport modes to bicycle commuting; 2) for bicycle commuting at peak morning commute times, inhaled particle counts and therefore cardiopulmonary health risk may be substantially reduced by decreasing exposure to motorised traffic, which should be considered by both bicycle commuters and urban planners; 3) exposure to PNC, and the incidence of offensive odour and nasopharyngeal irritation, can be significantly reduced when utilising a strategy of lowering proximity to motorised traffic whilst bicycle commuting, without significantly increasing commute distance or duration, which may bring important benefits for both healthy and susceptible individuals. In summary, the findings from this project suggests that bicycle commuters can significantly lower their exposure to ultrafine particle emissions by varying their commute route to reduce proximity to motorised traffic and associated combustion emissions without necessarily affecting their time of commute. While the health endpoints assessed with healthy individuals were not indicative of acute health detriment, individuals with pre-disposing physiological-susceptibility may benefit considerably from this risk management strategy – a necessary research focus with the contemporary increased popularity of both promotion and participation in bicycle commuting.

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Air pollution is a widespread health problem associated with respiratory symptoms. Continuous exposure monitoring was performed to estimate alveolar and tracheobronchial dose, measured as deposited surface area, for 103 children and to evaluate the long-term effects of exposure to airborne particles through spirometry, skin prick tests and measurement of exhaled nitric oxide (eNO). The mean daily alveolar deposited surface area dose received by children was 1.35×103 mm2. The lowest and highest particle number concentrations were found during sleeping and eating time. A significant negative association was found between changes in pulmonary function tests and individual dose estimates. Significant differences were found for asthmatics, children with allergic rhinitis and sensitive to allergens compared to healthy subjects for eNO. Variation is a child’s activity over time appeared to have a strong impact on respiratory outcomes, which indicates that personal monitoring is vital for assessing the expected health effects of exposure to particles.

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Background: Side effects of the medications used for procedural sedation and analgesia in the cardiac catheterisation laboratory are known to cause impaired respiratory function. Impaired respiratory function poses considerable risk to patient safety as it can lead to inadequate oxygenation. Having knowledge about the conditions that predict impaired respiratory function prior to the procedure would enable nurses to identify at-risk patients and selectively implement intensive respiratory monitoring. This would reduce the possibility of inadequate oxygenation occurring. Aim: To identify pre-procedure risk factors for impaired respiratory function during nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory. Design: Retrospective matched case–control. Methods: 21 cases of impaired respiratory function were identified and matched to 113 controls from a consecutive cohort of patients over 18 years of age. Conditional logistic regression was used to identify risk factors for impaired respiratory function. Results: With each additional indicator of acute illness, case patients were nearly two times more likely than their controls to experience impaired respiratory function (OR 1.78; 95% CI 1.19–2.67; p = 0.005). Indicators of acute illness included emergency admission, being transferred from a critical care unit for the procedure or requiring respiratory or haemodynamic support in the lead up to the procedure. Conclusion: Several factors that predict the likelihood of impaired respiratory function were identified. The results from this study could be used to inform prospective studies investigating the effectiveness of interventions for impaired respiratory function during nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory.

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Background: Procedural sedation and analgesia (PSA) administered by nurses in the cardiac catheterisation laboratory (CCL) is unlikely to yield serious complications. However, the safety of this practice is dependent on timely identification and treatment of depressed respiratory function. Aim: Describe respiratory monitoring in the CCL. Methods: Retrospective medical record audit of adult patients who underwent a procedure in the CCLs of one private hospital in Brisbane during May and June 2010. An electronic database was used to identify subjects and an audit tool ensured data collection was standardised. Results: Nurses administered PSA during 172/473 (37%) procedures including coronary angiographies, percutaneous coronary interventions, electrophysiology studies, radiofrequency ablations, cardiac pacemakers, implantable cardioverter defibrillators, temporary pacing leads and peripheral vascular interventions. Oxygen saturations were recorded during 160/172 (23%) procedures, respiration rate was recorded during 17/172 (10%) procedures, use of oxygen supplementation was recorded during 40/172 (23%) procedures and 13/172 (7.5%; 95% CI=3.59–11.41%) patients experienced oxygen desaturation. Conclusion: Although oxygen saturation was routinely documented, nurses did not regularly record respiration observations. It is likely that surgical draping and the requirement to minimise radiation exposure interfered with nurses’ ability to observe respiration. Capnography could overcome these barriers to respiration assessment as its accurate measurement of exhaled carbon dioxide coupled with the easily interpretable waveform output it produces, which displays a breath-by-breath account of ventilation, enables identification of respiratory depression in real-time. Results of this audit emphasise the need to ascertain the clinical benefits associated with using capnography to assess ventilation during PSA in the CCL.

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Impaired respiratory function (IRF) during procedural sedation and analgesia (PSA) poses considerable risk to patient safety as it can lead to inadequate oxygenation and ventilation. Risk factors that can be screened prior to the procedure have not been identified for the cardiac catheterization laboratory (CCL).