Airway inflammation, diagnosis, perception of asthma, and sputum zinc levels in a community cohort.

Induced sputum examination (IS), an established research tool to measure airway inflammation (AI), is normally confined to specialised institutions and selected populations with airway disease, especially asthma. This thesis examines the role of IS in the diagnosis of asthma in a community. The first study explores the accepted definitions of asthma, the utility of IS, and another marker of AI, exhaled nitric oxide (eNO), in establishing the diagnosis of asthma. The findings confirm that symptoms, variable airflow obstruction and airway hyper-responsiveness (AHR) are inter-linked in the definition of asthma. Bronchodilator reversibility (BDR), used traditionally, remains the most specific test to aid a diagnosis of asthma in the community. The results favour a tailored approach in the diagnosis of asthma using BDR initially, then selecting a test, either eNO or IS depending on the clinical scenario. The usefulness of AHR with hypertonic saline to diagnose asthma is equivocal given the moderate sensitivity and poor specificity of the test documented within. If a global assessment of AI is required, an eNO measurement is recommended initially, given its ease of use. Sputum examination is useful in delineating the subtype of AI present. Dyspnoea is a cardinal symptom in asthma. Studies have shown a correlation between AI measured by IS and an altered perception of dyspnoea (POD) in selected subjects with asthma. The aim of the second and third studies was to determine if a similar relationship exists in subjects with and without AHR from a community sample. In both groups, increasing POD was related to worsening lung function and increased BMI. Increased POD was also associated with poorer psychosocial and economic outcomes in subjects with AHR. In the context of previous research, these results illustrate that heightened POD itself, rather than asthma, is associated with these outcomes. Sputum eosinophilia was not associated with an altered POD in subjects with and without asthma. There has been mounting research establishing the role of zinc as an immunomodulator in asthma. Mouse models have demonstrated that zinc deficiency is associated with airway eosinophilia. Two pools of zinc exist in the body: largely fixed, enzyme-bound zinc, and free or labile zinc, the biologically active component. With zinc deficiency, it is the latter pool that is preferentially depleted. Our laboratory has developed a novel method, Zinquin fluorometry, allowing measurement of labile zinc in body fluids. The final two studies demonstrate that IS lends itself to labile zinc measurements. Zinquin fluorometry was optimised to measure free pools of zinc in sputum. It was then used to quantify labile sputum zinc concentrations in subjects with and without asthma. Lower zinc concentrations were found in the sputum of subjects with asthma and a significant association noted between lower zinc concentrations and worsening asthma severity. From a community perspective, these findings suggest that while IS has a limited role in diagnosing asthma, it lends itself to measurement of airway zinc. This work has been conducted in a cross-sectional community cohort where relationships were explored. Ongoing research is required to establish causal links conclusively.Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 201

Oxidations with 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ). Part III. Oxidation of spironaphthalenols. Synthesis of naphtho[2,1-b]furan derivatives.

Oxidn. of the spironaphthalenols I (R = H, Me, Ph) and II with DDQ gives the naphtho[2,1-b]furan derivs. (cis- and trans-III). The spectral properties (IR and NMR) of these compds. are discussed

Relationship between Sleep Duration and Risk Factors for Stroke

Stroke is a leading cause of death and disability worldwide. While various risk factors have been identified, sleep has only been considered a risk factor more recently. Various epidemiologic studies have associated stroke with sleep such as sleep duration, and laboratory and clinical studies have proposed various underlying mechanisms. The pathophysiology is multifactorial, especially considering sleep affects many common risk factors for stroke. This review aims to provide an outline of the effect of sleep duration on common stroke risk factors. Appropriate sleep duration, especially in patients who have stroke risk factors, and increasing awareness and screening for sleep quality may contribute to primary prevention of stroke

Neurological and Sleep Disturbances in Bronchiectasis

Bronchiectasis unrelated to cystic fibrosis is a chronic lung disease that is increasingly recognised worldwide. While other common chronic lung conditions such as chronic obstructive lung disease have been associated with cardiovascular disease, there is a paucity of data on the relationship between bronchiectasis and cardiovascular risks such as stroke and sleep disturbance. Furthermore, it is unclear whether other neuropsychological aspects are affected, such as cognition, cerebral infection, anxiety and depression. In this review, we aim to highlight neurological and sleep issues in relation to bronchiectasis and their importance to patient care

Bronchiectasis in the Last Five Years: New Developments

Bronchiectasis, a chronic lung disease characterised by cough and purulent sputum, recurrent infections, and airway damage, is associated with considerable morbidity and mortality. To date, treatment options have been limited to physiotherapy to clear sputum and antibiotics to treat acute infections. Over the last decade, there has been significant progress in understanding the epidemiology, pathophysiology, and microbiology of this disorder. Over the last five years, methods of assessing severity have been developed, the role of macrolide antibiotic therapy in reducing exacerbations cemented, and inhaled antibiotic therapies show promise in the treatment of chronic Pseudomonas aeruginosa infection. Novel therapies are currently undergoing Phase 1 and 2 trials. This review aims to address the major developments within the field of bronchiectasis over this time

Pulmonary cavitary Mycobacterium kyorinense (M. kyorinense) infection in an Australian woman

We describe a patient with pulmonary cavitary pneumonia from whom we serially isolated Mycobacterium kyorinense, an organism not previously reported in Australia, or associated with cavitary disease. We discuss the clinical presentation, the isolation of the organism on several specimens and initial management. M. kyorinense is a recently characterized species, which has previously only been described in Japan and Brazil [1]

Cost Analysis of Monitoring Asthma Treatment using Sputum Cell Counts

BACKGROUND: In a four-centre trial, the use of sputum cell counts (sputum strategy [SS]) to guide treatment had resulted in fewer and less severe exacerbations without the need for a higher corticosteroid dose, compared with the use of symptoms and spirometry (clinical strategy [CS])

The efficiency of sputum cell counts in cystic fibrosis

BACKGROUND: Technical factors relating to processing viscid sputum in cystic fibrosis (CF) and their influence on the reproducibility and validity of cell counts need to be evaluated. In addition, the methods need to be standardized so that they can be applied clinically and in research

Reaction of 4-cyano-1,3-dihydroxy-5,6,7,8-tetrahydroisoquinolines with vilsmeier reagent: structure and mechanism of formation of [2,7]naphthyridines

Reaction of 4-cyano-1,3-dihydroxy-5,6-7,8-tetrahydroisoquinoline 1, with Vilsmeier reagent gave the chloro aldehyde 2, dichloro [2,7]naphthyridine, 5 and monochloro [2,7]naphthyridine 8, identified by spectral data [Mass, 1H & 13C NMR, NOE and HETERO COSY]. Structure 5 has been confirmed by X-ray crystal structure analysis. Reaction of 1a-f, similarly, gave the corresponding compounds 2a-f, 5a-f and 8a-f. The starting tetrahydroisoquinolines, 1a-f were synthesised by the reaction of the corresponding β-keto esters with cyanoacetamide. Reaction of 8 with POCl3 gave in almost quantitative yield, the dichloro compound 5. An acceptable mechanism has been proposed for the formation of the products