Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 91
Filter
1.
Intern Med J ; 43(5): 507-12, 2013 May.
Article in English | MEDLINE | ID: mdl-23176301

ABSTRACT

BACKGROUND/AIMS: Recent data show great benefit from beta adrenergic blocking drug (ß-blocker) use in heart failure and has resulted in increased use of these established agents. Older data caution against their use in patients with reversible airways disease because of risks of bronchoconstriction. Anecdotally, we noted a difference in willingness to prescribe ß-blockers by cardiologists and respiratory physicians, especially for patients with coexisting airways disease. We sought to test this difference. METHODS: Nine clinical scenarios were created, tested and emailed to all members of the Cardiac and Thoracic societies of Australasia. Scenarios combined varying degrees of benefit and risk (bronchoconstriction). An inducement to return questionnaires was applied. RESULTS: Cardiologists and respiratory physicians were similarly willing to prescribe ß-blockers for patients at little risk of bronchoconstriction, irrespective of potential benefit. Cardiologists were more willing to prescribe ß-blockers than respiratory physicians for patients at greater risk of bronchoconstriction, particularly when the potential therapeutic benefit was greater. CONCLUSIONS: Our perception that cardiologists were more willing to prescribe ß-blockers than respiratory physicians was confirmed. This probably results from a difference in focus (namely focus on benefit by cardiologists vs focus on risk by respiratory physicians), although other factors including awareness of limitations of pulmonary function testing by respiratory physicians may have been involved. Until better tests are available (that discriminate between patients who are likely to suffer bronchoconstriction from those who are not), it is likely that this difference between the specialties will remain.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Cardiology/methods , Data Collection/methods , Drug Prescriptions , Physicians , Pulmonary Medicine/methods , Australasia , Choice Behavior , Humans , Physicians/psychology
2.
Curr Mol Pharmacol ; 1(1): 38-49, 2008 Jan.
Article in English | MEDLINE | ID: mdl-20021422

ABSTRACT

Airway epithelium (AE) lines the conducting airways of the respiratory system and functions to maintain airway integrity by providing both a physical barrier to inhaled noxious agents and a mechanism for their clearance via the mucociliary escalator. Normal AE cells are relatively refractory to a number of apoptotic stimuli and survival mechanisms are in place to maintain the integrity of the epithelial barrier that is exposed to agents such as reactive oxygen species (ROS) and death receptor ligands secreted by immune cells during inflammation. When damage to AE does occur, there is increased AE apoptosis, such as in the airway damage that occurs in the chronically inflamed airways in diseases like asthma where rates of AE apoptosis can be increased many-fold. The usual treatment for persistent asthma in humans involves a combination of bronchodilator and inhaled corticosteroid; there is however a need to develop strategies to better control other aspects of the disease, including minimizing the ongoing damage to AE and consequent airway remodeling. Targeting of the major apoptosis-regulatory factors in AE may be one such strategy. Here we review what is known about apoptosis and its regulatory factors in normal AE and abnormalities in these factors in the inflamed airways of mice and humans.


Subject(s)
Apoptosis Regulatory Proteins/antagonists & inhibitors , Apoptosis , Respiratory Mucosa/drug effects , Respiratory Tract Diseases/drug therapy , Airway Remodeling , Animals , Apoptosis Regulatory Proteins/metabolism , Asthma/drug therapy , Asthma/metabolism , Caspases/metabolism , Humans , Inflammation/drug therapy , Inflammation Mediators/metabolism , Mice , Necrosis , Respiratory Mucosa/metabolism
3.
Curr Drug Targets ; 7(5): 607-627, 2006 May.
Article in English | MEDLINE | ID: mdl-16719771

ABSTRACT

The dietary group IIb metal zinc (Zn) plays essential housekeeping roles in cellular metabolism and gene expression. It regulates a number of cellular processes including mitosis, apoptosis, secretion and signal transduction as well as critical events in physiological processes as diverse as insulin release, T cell cytokine production, wound healing, vision and neurotransmission. Critical to these processes are the mechanisms that regulate Zn homeostasis in cells and tissues. The proteins that control Zn uptake and compartmentalization are rapidly being identified and characterized. Recently, the first images of sub-cellular pools of Zn in airway epithelium have been obtained. This review discusses what we currently know about Zn in the airways, both in the normal and inflamed states, and then considers how we might target Zn metabolism by developing strategies to monitor and manipulate airway Zn levels in airway disease.


Subject(s)
Asthma/drug therapy , Carrier Proteins/physiology , Zinc/physiology , Absorption , Animals , Asthma/metabolism , Bronchi/metabolism , Cation Transport Proteins/physiology , Homeostasis , Humans , Trachea/metabolism , Zinc/administration & dosage , Zinc/deficiency
4.
Chron Respir Dis ; 2(3): 121-31, 2005.
Article in English | MEDLINE | ID: mdl-16281435

ABSTRACT

OBJECTIVES: To evaluate 1) barriers to clinical guideline use and 2) the relationship between guideline use and inpatient outcomes in chronic obstructive pulmonary disease (COPD). METHODS: 1) Four focus groups of specific health professions (n = 30), from three metropolitan hospitals, and interview of 99 medical officers (MOs), linked to 349 admissions, both guided by behavioural modelling theory; 2) association between guideline use and patient outcomes (length of hospital stay > or = 14 days, and readmission within 28 or 90 days) was evaluated in a cohort of 405 COPD patients. RESULTS: 1) In focus groups, nurses and allied health professionals emphasized facilitation issues including paperwork duplication and time limitations as barriers, but considered improved patient care outcomes as the major guideline use determinant. There were similar findings in junior MOs (nonconsultants) by both focus group and interview, with the addition of a need for a sense of ownership. Senior MOs (consultants) greatly emphasized sense of ownership. Barriers to guideline use varied between types of units. Behavioural modelling explained 49% of the variation in intention to use the guideline for MOs. For nonconsultants, habit and intention were significantly associated with extent of guideline use. 2) Patient outcomes: guideline use was not associated with length of stay or readmission. CONCLUSIONS: 1) Guideline implementation should address issues relevant to different health professions, units and seniority of profession. 2) Guideline use was not associated with reductions in readmission or length of stay.


Subject(s)
Evidence-Based Medicine/methods , Practice Guidelines as Topic , Pulmonary Disease, Chronic Obstructive/therapy , Adult , Aged , Clinical Competence , Female , Focus Groups , Follow-Up Studies , Hospitalization/statistics & numerical data , Humans , Male , Outcome Assessment, Health Care , Retrospective Studies
5.
Thorax ; 59(11): 930-5, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15516466

ABSTRACT

BACKGROUND: Reports of psychological conditions in asthmatic subjects have been limited to certain population groups or convenience samples. A study was undertaken of the prevalence of psychological distress in asthma in the general population and its associations with quality of life. METHODS: The WANTS Health and Well-being Survey is a population household interview survey of adults (age > or =18) in Western Australia, the Northern Territory, and South Australia. Data obtained were weighted to the closest census data to provide population representative estimates. Positive answers to two questions: "Have you ever been told by a doctor that you have asthma?" and "Do you still have asthma?" determined current doctor-diagnosed asthma. Other items included the SF-12, the Kessler-10 index of psychological distress, questions on feelings of lack of control in different areas of life, and on mental health conditions. RESULTS: From the available sample of 10 080, 7619 interviews were completed (participation rate 74.8%), with 834 people reporting current doctor-diagnosed asthma (11.2%). Psychological distress was more frequent in those with asthma (17.9% v 12.2%, p<0.01) and a higher proportion with asthma were at higher risk for anxiety or depression (40.5% v 31.2%, p<0.01). Mental health conditions were also more common (16.2% v 10.8%, p<0.01), as was the frequency of those who sometimes or always felt a lack of control over their health (33.5% v 24.3%, p<0.01). People with both asthma and psychological distress had significantly lower scores on the SF-12 physical component summary (PCS) than those with either asthma or distress alone. Among those with psychological distress, mental component summary (MCS) scores did not differ between asthmatic and non-asthmatic respondents. In a multiple regression model the frequency of a feeling of lack of control over health-together with age, family's financial situation, education level, and number of days partially unable to work or perform usual duties-was significantly associated with scores on the PCS (r = 0.73, adjusted r2 = 0.54). CONCLUSION: These results, from a representative population sample, show that psychological distress and decreased feelings of control are common in asthma and are significantly associated with physical health status.


Subject(s)
Asthma/psychology , Quality of Life , Stress, Psychological/etiology , Adolescent , Adult , Aged , Female , Humans , Male , Mental Health , Middle Aged , Regression Analysis , Surveys and Questionnaires
6.
Chron Respir Dis ; 1(1): 17-28, 2004.
Article in English | MEDLINE | ID: mdl-16281664

ABSTRACT

AIMS: Chronic obstructive pulmonary disease (COPD) is a common condition associated with considerable morbidity, mortality and hospital admissions. However, published COPD management guidelines have major limitations and lack practical summaries. We aimed to optimally develop, implement, and evaluate a multidisciplinary COPD inpatient management 'ACCORD' guideline, including prompts for comprehensive day one assessments through to a discharge criteria checklist. METHOD: Two intervention and two control public teaching hospitals in Adelaide, South Australia, took part, with pre-intervention (721 COPD admissions over 7 months) and intervention phases (509 COPD admissions over 7 months). During the intervention stage the ACCORD guideline was placed in the case notes on the day of admission or soon after. Readmissions were categorized as either emergency or elective and compared between the study arms, as were mortality and potential confounders (age, gender, number of comorbidities), with Poisson regression analysis. RESULTS: Of case notes of eligible COPD patients, 60% had the ACCORD guideline placed, of which 76% had evidence of use as judged by completion of guideline entry and tick boxes. The ACCORD guideline was associated with an increase in elective admissions and a reduction in emergency admissions in the intervention group in relation to the control group (P < 0.01), with no difference in overall admissions or death rates. CONCLUSIONS: The ACCORD guideline was associated with a shift from emergency admissions to more planned elective care, suggesting more proactive care of health problems, but without overall reduction in admissions.


Subject(s)
Hospital Mortality/trends , Inpatients , Patient Readmission/statistics & numerical data , Practice Guidelines as Topic , Pulmonary Disease, Chronic Obstructive/epidemiology , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Regression Analysis , South Australia/epidemiology
7.
Thorax ; 58(10): 846-50, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14514934

ABSTRACT

BACKGROUND: The prevalence of undiagnosed asthma in the general population and the clinical and demographic characteristics of these patients compared with those with diagnosed asthma are unclear. METHODS: The North West Adelaide Health Survey (NWAHS) is a population household interview survey of adults (age>18 years) in the north western suburbs of Adelaide, South Australia (regional population 0.6 million). Data obtained were weighted to the closest census data to provide population representative estimates. Positive answers to: "Have you ever had asthma?"; "Has it been confirmed by a doctor?"; "Do you still have asthma?" determined current physician diagnosed asthma. A positive bronchodilator response on spirometric testing according to ATS criteria without a physician's diagnosis determined undiagnosed asthma. Other measures included the SF-12 health survey questionnaire, the Selim index of severity of chronic lung disease, skin allergy tests, and demographic data. RESULTS: Of the 3422 individuals interviewed, 2523 (74%) agreed to participate in the clinical assessment. Of these, 292 (11.6%) had asthma, 236 (9.3%) with a doctor's diagnosis of asthma and 56 (2.3%) with undiagnosed asthma defined on spirometric criteria; thus, 19.2% of the total asthma group were undiagnosed. Those undiagnosed were more likely (p<0.05) to be >40 years old, on government benefits, with an income 65 years. Health service use over the previous year was similar for both asthma groups. CONCLUSION: Undiagnosed asthma is common among the Australian population, with a similar clinical spectrum to those with diagnosed asthma.


Subject(s)
Asthma/epidemiology , Adult , Aged , Asthma/diagnosis , Cost of Illness , Female , Forced Expiratory Volume/physiology , Humans , Male , Marital Status , Middle Aged , Odds Ratio , Prevalence , Risk Factors , South Australia/epidemiology , Vital Capacity/physiology
8.
J Paediatr Child Health ; 39(1): 15-21, 2003.
Article in English | MEDLINE | ID: mdl-12542806

ABSTRACT

OBJECTIVES: The present study aims to describe the use of health services by children with asthma, and examine disease-specific, parental and sociodemographic variables associated with different levels of health-service utilization. METHODS: Parents of 135 children attending an emergency room (ER) completed questionnaires measuring the children's asthma symptoms, and sociodemographic and psychological variables. Parents were contacted monthly for 6 months to document the number of planned and unplanned visits to hospital and community health-care services for asthma. RESULTS: At least one further unplanned visit to the ER was made by 37% of children, while 62% made at least one unplanned visit to a general practitioner (GP). Fifty-five per cent made planned review visits to a GP, 30% to paediatricians and 5% to hospital clinics. After controlling for the level of asthma symptoms, parental anxiety and parental perceptions of children's vulnerability were associated with unplanned GP visits (P = 0.05 and P = 0.01, respectively); a planned review visit and the child being admitted to hospital for the index attack were associated with unplanned ER visits (P = 0.05 and P = 0.004, respectively). CONCLUSIONS: Children with asthma more frequently attend GP services than hospital services for both planned and unplanned asthma management. Different variables predict the unplanned use of GP and ER services. Understanding these differences is imperative if children and families are to make the most effective use of health services.


Subject(s)
Asthma/therapy , Health Services/statistics & numerical data , Asthma/physiopathology , Child , Child, Preschool , Demography , Emergency Service, Hospital/statistics & numerical data , Family Practice/statistics & numerical data , Female , Health Services Research , Humans , Infant , Male , Outpatient Clinics, Hospital/statistics & numerical data , Socioeconomic Factors , South Australia , Utilization Review
9.
Am J Respir Crit Care Med ; 164(4): 536-41, 2001 Aug 15.
Article in English | MEDLINE | ID: mdl-11520711

ABSTRACT

An association has been reported between chronic infection with Chlamydia pneumoniae and the severity of asthma, and uncontrolled observations have suggested that treatment with antibiotics active against C. pneumoniae leads to an improvement in asthma control. We studied the effect of roxithromycin in subjects with asthma and immunoglobulin G (IgG) antibodies to C. pneumoniae > or = 1:64 and/or IgA antibodies > or = 1:16. A total of 232 subjects, from Australia, New Zealand, Italy, or Argentina, were randomized to 6 wk of treatment with roxithromycin 150 mg twice a day or placebo. At the end of 6 wk, the increase from baseline in evening peak expiratory flow (PEF) was 15 L/min with roxithromycin and 3 L/min with placebo (p = 0.02). With morning PEF, the increase was 14 L/min with roxithromycin and 8 L/min with placebo (NS). In the Australasian population, the increase in morning PEF was 18 L/min and 4 L/min, respectively (p = 0.04). At 3 mo and 6 mo after the end of treatment, differences between the two groups were smaller and not significant. Six weeks of treatment with roxithromycin led to improvements in asthma control but the benefit was not sustained. Further studies are necessary to determine whether the lack of sustained benefit is due to failure to eradicate C. pneumoniae.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Asthma/microbiology , Chlamydophila Infections/complications , Chlamydophila Infections/drug therapy , Chlamydophila pneumoniae , Pneumonia, Bacterial/complications , Pneumonia, Bacterial/drug therapy , Roxithromycin/therapeutic use , Adult , Anti-Bacterial Agents/pharmacology , Antibodies, Bacterial/blood , Asthma/classification , Asthma/diagnosis , Asthma/physiopathology , Chlamydophila Infections/blood , Chlamydophila Infections/diagnosis , Chlamydophila Infections/immunology , Chlamydophila pneumoniae/immunology , Chronic Disease , Double-Blind Method , Female , Follow-Up Studies , Forced Expiratory Volume/drug effects , Humans , Immunoglobulin G/immunology , Male , Middle Aged , Peak Expiratory Flow Rate/drug effects , Pneumonia, Bacterial/blood , Pneumonia, Bacterial/diagnosis , Pneumonia, Bacterial/immunology , Roxithromycin/pharmacology , Severity of Illness Index , Time Factors , Treatment Outcome
10.
Ann Allergy Asthma Immunol ; 86(3): 263-71, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11289322

ABSTRACT

OBJECTIVES: To identify factors associated with asthma patients' perceptions of the propensity of pulmonologists to involve them in treatment decision-making, and its association with asthma outcomes. DESIGN: Cross-sectional observational study performed from June 1995 to December 1997. SETTING: Pulmonary unit of a university teaching hospital. PATIENTS: Adult patients with asthma (n = 128). MEASUREMENTS AND RESULTS: By patient self-report, mean physician's participatory decision-making (PDM) style score was 72 (maximum 100, 95% CI 65, 79). PDM scores were significantly correlated (P < .0001) with the duration of clinic visits (r = .63), patient satisfaction (r = .53), duration of tenure of doctor-patient relationship (r = .37), and formal education (r = .22, P = .023). Significantly higher PDM style scores were reported when visits lasted longer than 20 minutes and when a patient had a >6-month relationship with a particular doctor. PDM scores were also significantly correlated with possession of a written asthma action plan (r = .54, P < .0001), days affected by asthma (r = .36, P = .0001), asthma symptoms (r = .23, P = .017), and preferences for autonomy in asthma management decisions (r = .28, P = .0035). Those with PDM scores <50 reported significantly lower quality of life for all domains of a disease-specific instrument and the Short-Form 36 health survey version 1.0. In multiple regression analysis, PDM style was associated with the length of the office visit and the duration of tenure of the physician-patient relationship (R2 = 0.47, P = .0009). The adjusted odds ratio, per standard deviation decrease in PDM scores, for an asthma hospitalization was 2.0 (95% CI 1.2, 3.2) and for rehospitalization was 2.5 (95% CI 1.2, 4.2). CONCLUSIONS: Patients' report of their physician's PDM style is significantly associated with health-related quality of life, work disability, and recent need for acute health services. Organizational factors, specifically longer visits and more time seeing a particular physician, are independently associated with more participatory visits. This has significant policy implications for asthma management.


Subject(s)
Asthma/psychology , Asthma/therapy , Patient Participation , Patient Satisfaction , Physician-Patient Relations , Adolescent , Adult , Aged , Asthma/diagnosis , Cross-Sectional Studies , Disease Management , Female , Health Status , Humans , Longitudinal Studies , Male , Middle Aged , Office Visits , Perception , Treatment Outcome
11.
Thorax ; 56(2): 126-32, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11209101

ABSTRACT

BACKGROUND: Lower patient preferences for autonomy in management decision making during asthma exacerbations have been associated with an increased risk for future hospital admissions. We sought to examine patient preferences for asthma self-management autonomy, and the clinical and psychosocial factors associated with autonomy preferences. METHODS: A cross sectional observational study was performed with data collected between June 1995 and December 1997 of 212 adult patients with moderate to severe asthma managed, at least in part, at two teaching hospitals. Subjects completed a survey of autonomy preferences, quality of life, clinical morbidity and health service use, asthma knowledge, self-efficacy, coping styles, and psychosocial measures. RESULTS: Patients preferred clinicians to assume the major role in most decision making about their management. However, patients wished to remain in control in choosing when to seek care and wanted to share decisions regarding initiating changes in medications during a moderate exacerbation. Multiple regression analysis showed that concerns about adverse effects of medications, education level, an active coping style, perceptions of the propensity of physicians to involve them in treatment decision making, and concerns about costs causing delays in seeking medical care were associated with preferences for autonomy in decision making. Autonomy preferences were not related to measures of concurrent clinical asthma control or health related quality of life. CONCLUSIONS: In a group of patients with moderate to severe asthma, a high proportion of whom were from socioeconomically disadvantaged backgrounds, education level, perceived physician behaviour, cost barriers to care, and psychosocial factors (but not clinical asthma control or management) were related to patient preferences for autonomy in management decision making during asthma exacerbations. This has implications for asthma action plans and design of self-management programmes.


Subject(s)
Asthma/therapy , Patient Participation , Adaptation, Psychological , Adolescent , Adult , Aged , Analysis of Variance , Asthma/psychology , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Multivariate Analysis , Patient Acceptance of Health Care , Self Efficacy , Socioeconomic Factors , Surveys and Questionnaires , Treatment Outcome
12.
Biometals ; 14(3-4): 315-30, 2001.
Article in English | MEDLINE | ID: mdl-11831462

ABSTRACT

In addition to its diverse role in many physiological systems, zinc (Zn) has now been shown to be an important regulator of apoptosis. The purpose of this review is to integrate previously published knowledge on Zn and apoptosis with current attempts to elucidate the mechanisms of action of this biometal. This paper begins with an introduction to apoptosis and then briefly reviews the evidence relating Zn to apoptosis. The major focus of this review is the mechanistic actions of Zn and its candidate intracellular targets. In particular, we examine the cytoprotective functions of Zn which suppress major pathways leading to apoptosis, as well as the more direct influence of Zn on the apoptotic regulators, especially the caspase family of enzymes. These two mechanisms are closely related since a decline in intracellular Zn below a critical threshold level may not only trigger pathways leading to caspase activation but may also facilitate the process by which the caspases are activated. Studies by our laboratory in airway epithelial cells show that Zn is co-localized with the precursor form of caspase-3, mitochondria and microtubules, suggesting this Zn is critically placed to control apoptosis. Further understanding the different pools of Zn and how they interact with apoptotic pathways should have importance in human disease.


Subject(s)
Apoptosis/physiology , Caspases/metabolism , Zinc/metabolism , Animals , Antioxidants/metabolism , Apoptosis/drug effects , Caspase 3 , Caspase 6 , Caspase 9 , Enzyme Activation/drug effects , Epithelial Cells/cytology , Epithelial Cells/metabolism , Homeostasis , Humans , Models, Biological , Necrosis , Respiratory System/cytology , Respiratory System/metabolism , Zinc/pharmacology
13.
Respirology ; 6(4): 297-304, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11844120

ABSTRACT

OBJECTIVE: Peak flow meters (PFM) continue to be recommended as an important part of asthma self-management plans. It remains unclear if there is an advantage in using PFM in people with moderate-to severe asthma who are not poor perceivers of bronchoconstriction. METHODOLOGY: Prospective, randomized controlled trial of 134 adults with moderate-to-severe asthma who did not have evidence of poor perception of bronchoconstriction on histamine challenge testing, who were recruited from inpatients and outpatients of a university teaching hospital. Comparison was made over 12 months of the effectiveness of written action plans using either peak flow monitoring or symptoms to guide management. Subjects were contacted at monthly intervals by telephone for reinforcement and evaluation of use of the action plans, and to provide ongoing education. Spirometry and PD20 histamine were measured at 3-monthly intervals. Measures of health care utilization and morbidity (asthma exacerbations; hospitalizations; emergency department (ED) visits; days absent from work or school due to asthma; medication use and a self-rating of asthma severity) were made monthly. A psychosocial questionnaire (attitudes and beliefs, state-trait anxiety, denial) was given at entry and at 12-months or at withdrawal from the study. RESULTS: There were significant improvements for both groups for hospitalizations, ED visits, days off from school or work, and PD20 histamine, but no between-group differences. Appropriate use of action plans was 85% in the symptoms group and 86% in the PFM group. For all subjects, those who subsequently had an ED visit had significantly higher levels of denial (P=0.04) and lower scores for self-confidence (P=0.04), compared to those who did not have an ED visit. CONCLUSIONS: Use of written action plans, combined with regular contact to reinforce self-management, improved airway reactivity and reduced health care utilization. However, use of PFM was not superior to symptom-based plans.


Subject(s)
Asthma/therapy , Adult , Asthma/diagnosis , Asthma/physiopathology , Bronchoconstriction/physiology , Health Services/statistics & numerical data , Humans , Patient Compliance , Peak Expiratory Flow Rate , Prospective Studies , Spirometry
14.
Am J Physiol Lung Cell Mol Physiol ; 279(6): L1172-83, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11076807

ABSTRACT

The respiratory epithelium is vulnerable to noxious substances, resulting in the shedding of cells and decreased protection. Zinc (Zn), an antioxidant and cytoprotectant, can suppress apoptosis in a variety of cells. Here we used the novel Zn-specific fluorophore Zinquin to visualize and quantify labile intracellular Zn in respiratory epithelial cells. Zinquin fluorescence in isolated ciliated tracheobronchial epithelial cells and intact epithelium from sheep and pigs revealed an intense fluorescence in the apical and mitochondria-rich cytoplasm below the cilia. Zinquin fluorescence was quenched by the Zn chelator N,N,N', N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) and increased by the Zn ionophore pyrithione. We also assessed whether changes in intracellular labile Zn would influence susceptibility of these cells to apoptosis by hydrogen peroxide. Our results confirm that Zn deficiency enhanced hydrogen peroxide-induced caspase activation from 1.24 +/- 0.12 to 2.58 +/- 0.53 units. microg protein(-1). h(-1) (P

Subject(s)
Apoptosis/physiology , Respiratory Mucosa/chemistry , Respiratory Mucosa/cytology , Zinc/analysis , Zinc/physiology , Adenocarcinoma, Bronchiolo-Alveolar , Animals , Apoptosis/drug effects , Bronchi/cytology , Butyrates/pharmacology , Caspase 3 , Caspases/metabolism , Chelating Agents/pharmacology , Coumarins/pharmacology , Drug Synergism , Enzyme Activation/drug effects , Epithelial Cells/chemistry , Epithelial Cells/enzymology , Epithelial Cells/ultrastructure , Ethylenediamines/pharmacology , Fluorescent Dyes , Humans , Hydrogen Peroxide/pharmacology , Lung Neoplasms , Microscopy, Electron , Microscopy, Fluorescence , Oligopeptides/pharmacology , Oxidants/pharmacology , Pulmonary Alveoli/cytology , Quinolones , Sheep , Swine , Tosyl Compounds , Trachea/cytology , Tumor Cells, Cultured/chemistry , Tumor Cells, Cultured/cytology , Tumor Cells, Cultured/enzymology
15.
Respirology ; 5(2): 125-31, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10894101

ABSTRACT

OBJECTIVE: To assess the change in bronchial response to cumulative doses from two beclomethasone dipropionate metered-dose inhalers (MDI), each using chlorofluorocarbon (CFC) propellants, in asthma patients previously showing falls in forced expiratory volume in 1 s (FEV1) shortly after exposure to beclomethasone MDI. METHODOLOGY: A total of 18 patients were randomized to a single-blind, three-period cross-over treatment regimen, whereby each was administered increasing doses of control mixture (containing surfactant and CFC propellants) or beclomethasone, formulated as either Becloforte or Respocort (250-1000 microg per dose; cumulative dose 2000 microg). Bronchial response was measured by comparison of FEV1 values pre- and post-inhalation. RESULTS: Respocort formulation produced the least post-dose mean maximum reduction in FEV1 (0.36 +/- 0.17 L; 14.3 +/- 7.2% of baseline FEV1), while the reduction caused by the control was similar (0.40 +/- 0.18 L; 16.2 +/- 9.9% of baseline FEV1). Becloforte produced a significantly greater maximum reduction in FEV1 than Respocort (0.55 +/- 0.32 L, P = 0.003; 22.0 +/- 15.3% of baseline FEV1, P = 0.005). No serious adverse events were reported, but four patients experienced falls in FEV1 of greater than 15% (three on Becloforte, one using the control). CONCLUSION: The incidence of falls in FEV1 following use of beclomethasone MDI was low and generally not serious even in a selected population. The Becloforte preparation produced significantly more post-dose bronchoconstriction than the Respocort formulation, perhaps because of differences in the composition of the surfactant and/or CFC propellant mixtures used to formulate each of the aerosols.


Subject(s)
Anti-Asthmatic Agents/adverse effects , Anti-Inflammatory Agents/adverse effects , Asthma/drug therapy , Beclomethasone/adverse effects , Bronchoconstriction/drug effects , Chlorofluorocarbons, Methane , Administration, Inhalation , Administration, Topical , Adult , Aged , Anti-Asthmatic Agents/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Asthma/physiopathology , Beclomethasone/administration & dosage , Cross-Over Studies , Female , Forced Expiratory Volume/drug effects , Glucocorticoids/adverse effects , Humans , Male , Middle Aged , Single-Blind Method , Surface-Active Agents
16.
Aust N Z J Med ; 30(2): 202-8, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10833111

ABSTRACT

BACKGROUND: Lung volume reduction surgery (LVRS) has been a frequent literature topic in emphysema management recently. Opinions differ in regard to usefulness, efficacy, and selection criteria. AIMS: To present the results of our first 55 bilateral videoscopically resected group, with follow-up of up to three years, and to present some of the local methodology problems faced. METHODS: Thirty-nine men and 16 women, age range 40-77, had either upper lobe (42), mixed (two), or lower lobe (11) resections without buttressing (except for unilateral buttressing in several of the latter patients as part of an intrapatient comparison trial) according to their pattern of emphysema determined by CT and perfusion scanning. RESULTS: Thirty day mortality was 5.5%. Follow-up pulmonary function is available for 44 patients, and demonstrates a mean 51% improvement in FEV1, and significant improvement in FVC, PaO2, dyspnoea indices and walking distance, with a reduction in mean RV, TLC, PaCO2. FEV1 improvement is maintained above baseline at three years. Lower lobe surgery outcomes are at least as good as their upper lobe counterparts. CONCLUSIONS: Outcomes confirm improvements reported elsewhere, and suggest that videoscopic resection may provide worthwhile benefit to lower lobe patterns of emphysema. Other managment issues are discussed.


Subject(s)
Pneumonectomy , Pulmonary Emphysema/surgery , Thoracic Surgery, Video-Assisted , Activities of Daily Living , Adult , Aged , Cost-Benefit Analysis , Female , Forced Expiratory Volume , Health Care Costs , Humans , Male , Middle Aged , Pneumonectomy/economics , Postoperative Complications , Pulmonary Emphysema/mortality , Respiratory Mechanics , South Australia/epidemiology , Survival Rate , Thoracic Surgery, Video-Assisted/economics
17.
Thorax ; 55(7): 566-73, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10856316

ABSTRACT

BACKGROUND: A small proportion of patients with asthma account for a disproportionate number of acute health service events. To identify whether factors other than severity and low socioeconomic status were associated with this disproportionate use, a prospective study was undertaken to examine management and psychosocial factors associated with increased risk for admission to hospital with asthma and repeat visits to the emergency department over a 12 month period. METHODS: A total of 293 patients with moderate or severe asthma managed at least in part at two teaching hospitals completed surveys of clinical status, acute events, sociodemographic, and psychological variables. RESULTS: Twenty three percent had a single admission to hospital and 16% had two or more hospital admissions. Twenty six percent had one emergency department visit and 32% had two or more visits to the emergency department. In a multiple logistic regression model, adjusted for age, sex, education and income, odds ratios (95% CI) for baseline factors associated with hospital admissions over the next 12 months were: moderate severity compared with severe asthma 0.6 (0.2 to 0.9); no hospital admissions in the past 12 months 0.1 (0.01 to 0.2); not possessing a written asthma action plan 4.0 (1.5 to 10.7); less use of an avoidance coping style 0.4 (0.3 to 0.7); lower preferences for autonomy in asthma management decisions 1.4 (0.96 to 2.0). Adjusted odds ratios (95% CI) for repeat emergency department visits were: moderate asthma severity 0.3 (0.1 to 0.8); current regular use of oral corticosteroids 10.0 (3.1 to 32.4); a hospital admission in the past 12 months 2.9 (1.8 to 4.8); not possessing a written asthma action plan 2.2 (1.1 to 5.6); less dislike of asthma medications 0.7 (0.5 to 0.9). CONCLUSIONS: In addition to factors relating to severity, not possessing a written asthma action plan, avoidance coping, and attitudes to self-management were related to acute use of health services in this at risk group. Interventions need to address or take these factors into account to reduce asthma morbidity.


Subject(s)
Asthma/therapy , Attitude to Health , Emergency Service, Hospital/statistics & numerical data , Hospitalization/statistics & numerical data , Adolescent , Adult , Aged , Asthma/psychology , Educational Status , Emergencies , Female , Forced Expiratory Volume/physiology , Health Status , Humans , Longitudinal Studies , Male , Middle Aged , Peak Expiratory Flow Rate/physiology , Prospective Studies , Risk Factors , Social Class
18.
J Asthma ; 37(2): 131-43, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10805202

ABSTRACT

To produce a scale useful for individual clinical decision making, the Marks Asthma Quality of Life Questionnaire (AQLQ-M) was modified to a 22-item scale using a 7-point Likert response scale, and the validity of the new instrument was assessed. Adult asthma subjects with moderate to severe disease, recruited from two hospitals in Adelaide, Australia, were surveyed at baseline (n = 293), and at 3-month follow-up (n = 234). Cronbach's alpha for the Total scale of the modified AQLQ-M (MAQLQ-M) was 0.97 and all subscale values exceeded 0.90. Test-retest reliability values for all scales were between 0.88 and 0.93. All correlations between disease reference measures were statistically significant to at least the p < 0.01 level. Stronger associations were seen with symptom and self-rating scales than for lung function, medication usage, and health service utilization measures of outcome. The MAQLQ-M showed good discriminative ability for all asthma symptom categories and for different FEV1 values. Moderate, statistically significant associations were seen between changes in MAQLQ-M scores and clinical measures. Higher baseline MAQLQ-M scores were associated with lower risks over 12 months for hospital admissions (odds ratio, OR = 0.58) and repeated emergency department visits (OR = 0.47). The MAQLQ-M is a highly valid measure of asthma-related quality of life.


Subject(s)
Asthma/diagnosis , Quality of Life , Surveys and Questionnaires , Adult , Asthma/psychology , Factor Analysis, Statistical , Female , Humans , Linear Models , Male , Reproducibility of Results
19.
Med J Aust ; 172(2): 62-6, 2000 Jan 17.
Article in English | MEDLINE | ID: mdl-10738474

ABSTRACT

OBJECTIVES: To describe patterns of hospital readmission for asthma in South Australia from 1989 to 1996, in relation to implementation of the National Asthma Campaign. DESIGN AND SETTING: A comparison of hospital admissions in South Australia of patients aged between one year and 49 years for three conditions: asthma (or respiratory failure with asthma as an underlying condition) and two control conditions--diabetes and epilepsy. Individuals were identified by Medicare number and date of birth. OUTCOME MEASURES: Hospital readmission within 28 days and within one year. RESULTS: Overall, by 1996, there was a statistically significant decline in the risk of readmission for asthma within 28 days of 18% and within one year of 17% compared with 1989 readmission rates. There were no reductions in the risk of readmission for diabetes or epilepsy, suggesting that the decline in risk of readmission for asthma was greater than the underlying effects of general changes in hospital casemix. CONCLUSIONS: The decline in risk of readmission may reflect changes in asthma severity or improved management practices. However, hospital readmission rates still remain high, and to further reduce readmissions for asthma there is a need to identify factors related to presentation for asthma at accident and emergency departments.


Subject(s)
Asthma/epidemiology , Health Promotion/trends , Patient Readmission/statistics & numerical data , Adolescent , Adult , Asthma/prevention & control , Australia/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Diabetes Mellitus/epidemiology , Diabetes Mellitus/prevention & control , Epilepsy/epidemiology , Epilepsy/prevention & control , Female , Health Plan Implementation/trends , Humans , Incidence , Infant , Male , Middle Aged , Program Evaluation
20.
Eur Respir J ; 15(2): 426-9, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10706517

ABSTRACT

Pulmonary alveolar proteinosis is a rare condition characterized by the abnormal accumulation of surfactant-like material within the alveolar spaces and distal bronchioles. Two cases with contrasting modes of presentation, course, and response to therapeutic whole lung lavage are described. Both cases were in hypoxaemic respiratory failure at the time the definitive diagnosis was made, and in both cases the diagnosis was made by segmental bronchoalveolar lavage following negative open lung biopsy. In neither was an underlying causative organism or agent identified. In one case the alveolar proteinosis developed in late pregnancy, a presentation that is previously unreported. Clinical improvement in this case required repeated whole lung lavages and was accompanied by a trend towards normalization of the ratios of surfactant protein-A and surfactant protein-B to disaturated phospholipid, ratios which may be useful as prognostic indicators. The response to therapeutic lavage was markedly different in the two cases, and it is postulated that this may relate to the fact that alveolar proteinosis is a heterogeneous disease and that the course and response to treatment may relate in part to the specific composition of the abnormal proteinaceous fluid.


Subject(s)
Pulmonary Alveolar Proteinosis , Adult , Bronchoalveolar Lavage , Female , Humans , Male , Pregnancy , Pregnancy Complications/diagnosis , Pregnancy Complications/therapy , Pulmonary Alveolar Proteinosis/diagnosis , Pulmonary Alveolar Proteinosis/therapy
SELECTION OF CITATIONS
SEARCH DETAIL
...