Emeritus Professor Michael Hensley

INTRODUCTION: Sleep apnoea is the popular term for obstructive sleep apnoea-hypopnoea syndrome (OSAHS). OSAHS is abnormal breathing during sleep that causes recurrent arousals, sleep fragmentation, excessive daytime sleepiness, and nocturnal hypoxaemia. Apnoea may be "central", in which there is cessation of inspiratory effort, or "obstructive", in which inspiratory efforts continue but are ineffective because of upper airway obstruction. OSAHS affects up to 4% of men and 2% of women in the USA, with obesity being a major determinant.

First major evidence-based text in adult respiratory medicine. Comprehensive, authoritative summary of the best treatments for the major respiratory diseases. Compiled by specialists from the Cochrane Airways Management Group. Easy-to-use format, with key clinical implications summarised in each chapter. Kept up-to-date online: Compiled by specialists from the Cochrane Collaboration Airways Management Group, Evidence-based Respiratory Medicine is the first major evidence-based text in adult respiratory medicine. Providing a comprehensive summary of the best treatments for the most important respiratory diseases, some of the world's leading physicians review the evidence for a broad range of treatments using evidence-based principles. Essential information is presented in an easy-to-understand format, with the most important clinical implications summarised in each chapter. Evidence-based Respiratory Medicine tackles the big clinical questions in diagnosis and treatment, presenting treatment options which take into account the individual patient's needs. Evidence-Based Series:Evidence-based Respiratory Medicine, part of the acclaimed series BMJ Evidence-based medicine textbooks that have revolutionised clinical medicine literature, comes with a fully searchable CD-ROM of the whole text. Note: CD-ROM/DVD and other supplementary materials are not included as part of eBook file. © 2005 by Blackwell Publishing Ltd.

BACKGROUND: Lung volume reduction surgery (LVRS) has been re-introduced for treating patients with severe diffuse emphysema. It is a procedure that aims to improve long-term daily functioning, although it is costly and may also be associated with a high risk of mortality. OBJECTIVES: To assemble evidence from randomised controlled trials for the effectiveness of LVRS, and identify optimal surgical techniques. SEARCH STRATEGY: Randomised controlled trials were identified using the Cochrane Airways Group Chronic Obstructive Pulmonary Disease (COPD) register. Searches are current to September 2005. SELECTION CRITERIA: Randomised controlled trials that studied the safety and efficacy of LVRS in patients with diffuse emphysema were included. Studies were excluded if they investigated giant or bullous emphysema. DATA COLLECTION AND ANALYSIS: Two independent review authors assessed trials for inclusion and extracted data. Where possible, data from more than one study were combined using RevMan 4.2 software. MAIN RESULTS: Eight studies (1663 participants) met the entry criteria of the review. One study accounted for 73% of the participants recruited. Study quality was high, although blinding in studies was not possible. Ninety day mortality was significantly greater in all those who underwent LVRS (odds ratio 6.57 (95% CI 3.34 to 12.95), four studies, N = 1415). A subgroup analysis by risk status suggested that there was a subgroup of participants who were consistently at a significant risk of death, although this was only measured in one large study. The ninety day mortality data indicated that death was more likely with LVRS irrespective of risk status identified in one large study. Improvements in lung function, quality of life and exercise capacity were more likely with LVRS than with usual follow-up. AUTHORS' CONCLUSIONS: The evidence summarised in this review is drawn from one large study, and several smaller trials. The findings from the large study indicated that in patients who survive up to three months post-surgery, there were significantly better health status and lung function outcomes in favour of surgery compared with usual medical care. Patients identified post hoc as being of high risk of death from surgery were those with particularly impaired lung function and poor diffusing capacity and/or homogenous emphysema. Further research should address the effect of this intervention on exacerbations and rate of decline in lung function and health status.

Background: A key component of many asthma management guidelines is the recommendation for patient education and regular medical review. A number of controlled trials have been conducted to measure the effectiveness of asthma education programmes. These programmes improve patient knowledge, but their impact on health outcomes is less well established. At its simplest level, education is limited to the transfer of information about asthma, its causes and its treatment. This review focused on the effects of limited asthma education. Objectives: The objective of this review was to assess the effects of limited (i.e. information only) asthma education on health outcomes in adults with asthma. Search methods: We searched the Cochrane Airways Group trials register and reference lists of articles. Selection criteria: Randomised and controlled trials of individual asthma education involving information transfer only in adults over 16 years of age. Data collection and analysis: Trial quality was assessed and two reviewers extracted data independently. Study authors were contacted for missing information. Main results: Twelve trials were included. They were of variable quality. Limited asthma education did not reduce hospitalisation for asthma (weighted mean difference -0.03 average hospitalisations per person per year, 95% confidence interval -0.09 to 0.03). There was no significant effect on doctor visits, lung function and medication use. The effects on asthma symptoms were variable. There was no reduction in days lost from normal activity, but in two studies, perceived asthma symptoms did improve after limited asthma education (odds ratio 0.44, 95% confidence interval 0.26 to 0.74). In one study, limited asthma education was associated with reduced emergency department visits (reduction of -2.76 average visits per person per year, 95% confidence interval -4.34 to 1.18). Authors' conclusions: Use of limited asthma education as it has been practiced does not appear to improve health outcomes in adults with asthma although perceived symptoms may improve. Provision of information in the emergency department may be effective, but this needs to be confirmed.

The efficacy of BiPAP in acute respiratory failure in chronic obstructive pulmonary disease (COPD) is established, but challenges remain in introducing this into clinical practice. To facilitate this we devised a clinical pathway (CP) that combines treatment from intensive care and the respiratory ward. The aim of this study was to assess our ability to implement BiPAP treatment via this CP. Method: A retrospective case controlled study was undertaken. Consecutive subjects presenting with acute hypercapnoeic respiratory failure secondary to COPD were commenced on the BiPAP clinical pathway (n=17). They were compared to controls matched according to sex, age and severity of acute and chronic respiratory disease (n=34). Results: Only 1 subject treated with BiPAP needed to be intubated compared to 20 controls (p<0.01). The BiPAP group spent a mean of 22.9 hours in the ICU compared with 104 hours for the controls (pO.OOl), and had a mean length of stay in hospital of 7.9 days compared to 12.6 days in the controls (p=0.01). There was 1 death in the Bi PAP group and 7 in the control group (p=0.2). Conclusion: The introduction of BiPAP treatment through a CP has resulted in a significant improvement in patient outcomes and length of stay.

BACKGROUND: Lung volume reduction surgery (LVRS) has been re-introduced for treating patients with severe diffuse emphysema. OBJECTIVES: To assemble evidence from randomised controlled trials for the effectiveness of LVRS, and identify optimal surgical techniques, those patients who benefit most and those for whom it should be avoided. SEARCH STRATEGY: Randomised controlled trials were identified using the Cochrane Airways Group COPD register using the terms: emphysema AND (emphysema surgery OR lung volume reduction surgery OR LVRS OR volume reduction surgery OR pneumectomy OR reduction pneumoplasty OR lung reduction surgery). The Cochrane Controlled Clinical Trials Register was also searched using these terms. SELECTION CRITERIA: Randomised controlled trials that studied the safety and efficacy of LVRS in patients with diffuse emphysema were included. Studies were excluded if they investigated giant or bullous emphysema. DATA COLLECTION AND ANALYSIS: Two independent reviewers assessed trials for inclusion and extracted data. MAIN RESULTS: Only one randomised trial of LVRS for diffuse emphysema was identified. This compared stapled unilateral thoracoscopic lung reduction coupled with bovine pericardium reinforcement with a unilateral neodymium:yttrium aluminium garnet laser contact reduction. A total of 72 patients were studied. Both arms included post-operative rehabilitation and appeared to be well matched at randomisation. Improvement in FEV1 & FVC at six months was significantly greater in the staple treated group (p < 0.01 & p < 0. 07 respectively), but absolute increases were small. Need for supplemental oxygen was reduced significantly more in the staple treated group; Peto Odds Ratio (OR) 4.05; 95% confidence interval (CI) 1.40, 11.71. Quality of life improved more in the staple treated group (OR 5.36; 95% CI 2.13,13.47). The rate of delayed pneumothorax in the laser treated group was significantly higher (OR 10.46; 95% CI 1.98, 55.30). REVIEWER'S CONCLUSIONS: There is no randomised controlled trial evidence concerning the efficacy of LVRS for diffuse emphysema compared to optimal conservative medical therapy. Stapling is more effective than laser resection and has a lower complication rate. LVRS should not be applied routinely until results of large trials currently underway become available.

BACKGROUND: A key component of many asthma management guidelines is the recommendation for patient education and regular medical review. A number of controlled trials have been conducted to measure the effectiveness of asthma education programmes. These programmes improve patient knowledge, but their impact on health outcomes is less well established. At its simplest level, education is limited to the transfer of information about asthma, its causes and its treatment. This review focused on the effects of limited asthma education. OBJECTIVES: The objective of this review was to assess the effects of limited (i.e. information only) asthma education on health outcomes in adults with asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and reference lists of articles. SELECTION CRITERIA: Randomised and controlled trials of individual asthma education involving information transfer only in adults over 16 years of age. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. Study authors were contacted for missing information. MAIN RESULTS: Eleven trials were included. They were of variable quality. Limited asthma education did not reduce hospitalisation for asthma (weighted mean difference -0.03 average hospitalisations per person per year, 95% confidence interval -0.09 to 0.03). There was no effect on doctor visits, lung function and medication use. The effects on asthma symptoms were variable. There was no reduction in days lost from normal activity, but perceived asthma symptoms did improve after limited asthma education (odds ratio 0.40, 95% confidence interval 0.18 to 0.86). In one study, limited asthma education was associated with reduced emergency department visits (weighted mean difference -2.76 average visits per person per year, 95% confidence interval -4.34 to 1.18). REVIEWER'S CONCLUSIONS: Use of limited asthma education as it has been practiced does not appear to improve health outcomes in adults with asthma. However the use of information in the emergency department may be effective, but this needs to be confirmed.

BACKGROUND: A key component of many asthma management guidelines is the recommendation for patient education and regular medical review. A number of controlled trials have been conducted to measure the effectiveness of asthma education programmes. These programmes improve patient knowledge, but their impact on health outcomes is less well established. This review was conducted to examine the strength of evidence supporting Step 6 of the Australian Asthma Management Plan: "Educate and Review Regularly"; to test whether health outcomes are influenced by education and self-management programmes. OBJECTIVES: The objective of this review was to assess the effects of asthma self-management programmes, when coupled with regular health practitioner review, on health outcomes in adults with asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and reference lists of articles. SELECTION CRITERIA: Randomised trials of self-management education in adults over 16 years of age with asthma. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. Study authors were contacted for confirmation. MAIN RESULTS: Twenty-five trials were included. Self-management education was compared with usual care in 22 studies. Self-management education reduced hospitalisations (odds ratio 0.57, 95% confidence interval 0.38 to 0.88); emergency room visits (odds ratio 0.71, 95% confidence interval (0.57 to 0.90); unscheduled visits to the doctor (odds ratio 0.57, 95% confidence interval 0.40 to 0.82); days off work or school (odds ratio 0.55, 95% confidence interval 0.38 to 0. 79); and nocturnal asthma (odds ratio 0.53, 95% confidence interval 0.39 to 0.72). Measures of lung function were little changed. Self-management programmes that involved a written action plan showed a greater reduction in hospitalisation than those that did not (odds ratio 0.35, 95% confidence interval 0.18 to 0.68). People who managed their asthma by self-adjustment of their medications using an individualised written plan had better lung function than those whose medications were adjusted by a doctor. REVIEWER'S CONCLUSIONS: Training in asthma self-management which involves self-monitoring by either peak expiratory flow or symptoms, coupled with regular medical review and a written action plan appears to improve health outcomes for adults with asthma. Training programmes which enable people to adjust their medication using a written action plan appear to be more effective than other forms of asthma self-management.

Allergic bronchopulmonary aspergillosis (ABPA) is a serious complication of asthma. In uncomplicated asthma airway inflammation(ai) is characterised by sputum eosinophilia without an increase in the total cell count (TCC). In bronchiectasis the intensity of ai increased and there is a neutrophil infiltrate. Airway inflammation in ABPA is not well defined. This study tested the hypothesis that ai in ABPA would be of increased intensity with a mixed eosinophil/neutrophil pattern. Methods: In subjects with asthma, ABPA was assessed by 5 criteria; 1. positive allergy skin test to Aspergillus Fumigatus (Af); 2. raised specific serum IgE to Af; 3. positive precipitating antibodies to Af; 4. total IgE > 10001U/ml and 5. bronchiectasis (CT scan). Subjects were classified as definite ABPA (n=13) with criteria 1, 2, 3 and either 4 or 5; or as probable ABPA (n=18) with 1 and 2 and either 3, 4 or 5 (n=13). These groups were combined for analysis. Af sensitised subjects (n=19 with positive skin testing alone), were compared to a matched group with asthma (negative to Af on skin test) (n=15) and healthy controls (n=8). Spirometry, saline challenge and sputum induction were performed, with results reported as medians and interquartile ranges. Results: Patients with ABPA had an increased TCC (4.6, 0.9-29.6) compared to: Af sensitised (3.6, 1.4-7.4), asthma (1.5, 0.8-3.2), and controls (1.35, 1.3-1.4) (p<0.05). Those with ABPA had increased sputum eosinophils (3.8, 0.3-16.3), compared to: Af sensitised (1.4, 0.1-6), asthma (1.6, 0.01-3), and controls (0.3, 0.3-0.31 ) (p=0.001). Those with ABPA had increased levels of eosinophil cationic protein(ng/ml) (5471, 311-42485) compared to: Af sensitised (1432, 338-6902), asthma (244, 78-857), and controls (110, 99-121 ) (p<0.001). Neutrophil counts were similar in all groups. Myeloperoxidase was similar in ABPA (232, 66-454) and asthma (177, 57-318) (p=0.3) but greater than in healthy controls (76, 76-89) Conclusion: Airway inflammation in ABPA is of increased intensity compared to that of chronic asthma. Unlike bronchiectasis, the cellular infiltrate is predominantly eosinophilic. The eosinophils demonstrate increased activation.

The authors carried out a population-based case-control study to estimate the risk of an acute coronary disease event associated with various definitions of a family history of coronary heart disease (CHD). A detailed family history questionnaire was completed by 403 cases and 236 controls in Newcastle, New South Wales, Australia from 1992 to 1994. Odds ratios of an acute coronary disease event adjusted for proband age and sex ranged from 2.7 (95% confidence interval (CI) 1.8-4.1) for the simplest definition (one or more first-degree relatives with CHD at any age) to 5.4 (95% CI 1.7-16.8) for the most stringent definition (two or more first-degree relatives with CHD before age 55 years). In a series of nested models, the authors examined the improvement in model fit as each component of the detailed family history was added. Additional information was provided by accounting for 'don't know' responses, the number of affected relatives, the age of the affected relative, and whether the first-degree relative was a sibling rather than a parent. The results were similar when the data were analyzed as a cohort design with proband disease status as the exposure variable. The authors suggest that, to facilitate preventive efforts in a population, more detailed family history definitions should be used to better target high risk subjects.

To determine the effect of inhaled corticosteroid use on the development of cataracts in older adults. Design Community-based study with data collected during 1992 and 1993. Setting District general hospital west of Sydney, Australia. Patients 4433 patients who were born before 1943 were identified by door-to-door census and invited to attend the study clinic for an eye examination. 3654 attended, of whom 3313 (mean age 66 y, 57% women) provided information on corticosteroid use. Assessment of risk factors Patients completed questionnaires specifying inhaled corticosteroid use (currently, in the past, or never). Investigators categorized beclomediasone use for usual number of puffs/wk and cal-culated the estimated lifetime dose. Other risk factors assessed were history of smoking, diabetes, and hypertension; socioeconomic status; and sun-related skin damage. Main outcome measures Nuclear cataracts were identified, and their severity was graded by comparing photographs of the patients' eyes with 4 standard photographs; cortical and posterior subcapsular cataracts were graded by estimating the percentage of the lens covered by opacity. Relative-prevalence (RP) ratios were calculated for each type of cataract. Main results The rates of posterior subcapsular, cortical, and nuclear cataracts were 6%, 24%, and 19%, respectively. 11% of participants had used inhaled corticosteroids. The use of inhaled corticosteroids at any time was associated with increased prevalence of nuclear cataracts (RP 1.5,95% CI 1.2 to 1.9) and posterior subcapsular cataracts (RP 1.9, CI 1.3 to 2.8). Higher cumulative lifetime doses of beclomethasone were associated with increased prevalence of posterior subcapsular cataracts. For a lifetime dose of beclomethasone A 2 000 mg among current users, the RP for posterior subcap-sular cataracts was 5.5 (CI 2.3 to 13.0, P for trend < 0.001). The prevalence of nuclear cataracts was also greater at that dose of beclomethasone (RP 4.0, CI 1.8 to 9.3). An increased prevalence of cortical cataracts was seen only with current use of inhaled corticpsteroids (RP 1.4, CI 1.1 to 1.7). Adjustment for risk factors, including systemic corticosteroid use, did not affect the strength of the association between inhaled corticosteroid use and the presence of posterior subcapsular cataracts (odds ratio for lifetime dose of beclomethasone a 2000 mg 10.0, CI 3.3 to 33.2, P for trend < 0.001). Conclusion Use of inhaled corticosteroids was associated with increased risk for the development of nuclear and posterior subcapsular cataracts.

To compare the efficacy of an influenza hemagglutinin-diphtheria toxoid conjugate vaccine with the commercially available influenza hemagglutinin-subunit vaccine in preventing influenza in older adults living in a nursing home. A prospective, randomized, double-blind vaccine trial with 5 months of follow-up after vaccination. Fourteen Wisconsin nursing homes. Nursing home residents at least 65 years old who were able to give informed consent and were free of malignancy and not receiving immunosuppressive therapy. Participants received, by intramuscular injection, 0.5 mL of a trivalent influenza vaccine containing 15 µg each of A/Leningrad/360/86 (H3N2), A/Taiwan/1/86 (H1N1), and B/Ann Arbor/1/86 (HA) or 0.5 mL of an influenza vaccine containing the same antigens conjugated to diphtheria toxoid (HA-D). Blood was obtained pre- and 1 month post-vaccination to assess for any vaccine-induced antibody titer change. Clinical surveillance for respiratory illness was performed twice weekly for 5 months. A record was kept of all signs and symptoms of new respiratory illness, and a viral culture and acute and convalescent sera were obtained. 204 participants received HA and 204 received HAD. Both groups had similar baseline antibody levels to all influenza antigens. HA-D recipients seroconverted more frequently based on serum neutralizing activity (P < 0.05), had a greater increase in geometric mean titer (GMT), and sustained the increase in antibody titer longer than HA recipients. Vaccine hemagglutinin recall was greater in a subset of HA-D recipients as measured by lymphocyte proliferative assays (P < 0.05). During an outbreak of influenza A (H3N2 A/Shanghai/11/87-like and A/Victoria/7/87-like), fewer HA-D (29/195) than HA (43/204) recipients had laboratory-confirmed infection (P = 0.053), and, of these, fewer HA-D-treated subjects had lower respiratory tract involvement (5/29 HA-D and 17/43 HA) (P = 0.022). HA-D was more immunogenic in institutionalized elderly recipients and produced greater protection from influenza infection. Superior protection may be due to HAD's ability to stimulate and recruit antigen-presenting cells, thus enabling the recipient to achieve and maintain functional antibody titers. © 1994 The American Geriatrics Society

During a prospective study of the ontogeny of the mucosal immune system using saliva, one subject acquired a selective IgA deficiency at 3 years 6 months of age. Prior to this time the infant had normal ontogeny patterns for salivary immunoglobulins and the salivary IgA was confirmed to be dimeric IgA containing secretory component. Two respiratory tract infections at 3 years 4 months and 3 years 5 months were reported prior to the collection of a saliva sample which was deficient in IgA. All subsequent saliva collections remained IgA deficient. Serum and saliva collected at 11 years of age confirmed persistent IgA deficiency. There was a family history of organ-specific autoimmune disease. The prospectively collected data indicate in this subject that the IgA deficiency was not congenital, but was acquired closely associated with two episodes of respiratory tract infections, against a genetic background of disturbed immune regulation. Copyright © 1994, Wiley Blackwell. All rights reserved

The new International Union Against Tuberculosis (IUAT) bronchial symptoms questionnaire was completed by 827 subjects participating in a prospective study of respiratory symptoms and lung function in aluminum smelter workers. A modified Medical Research Council (MRC) questionnaire was also administered. Bronchial reactivity (BR) was measured in 809 subjects by metha-choline challenge using a rapid method. Factor analysis demonstrated sensible clustering of responses to items unqiue to the new questionnaire such as nocturnal, spontaneous, and postexertional dyspnea, dust-induced dyspnea and tightness, and breathing difficulty. Responses to IUAT questions concerning past asthma, wheeze, chest tightness, morning cough and sputum, and asthma medication agreed well with corresponding items from the MRC questionnaire. Questions concerning asthma, medication, dust-induced, nocturnal, and spontaneous dyspnea, chest tightness, wheeze, nocturnal cough, postex-ertional dyspnea and breathing difficulty also had high validity against the criterion of concurrently measured bronchial reactivity. It is concluded that the IUAT questionnaire is a valid asthma questionnaire. © 1991 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

The measurement of bronchial reactivity in epidemiological studies has the advantage of quantifying an objective physiological feature of asthma. Bronchial reactivity was developed in a clinical setting and has been conventionally expressed as the dose of agonist producing a 20% fall in FEV1 (PD20). As PD20 can be estimated for less than 20% of subjects in general community surveys with the doses of agonist that are usually given, data from most subjects must be censored. Thus PD20 alone is a poor index of bronchial reactivity for epidemiological studies. Data from 809 aluminium smelter workers were used to evaluate alternative methods of analysing bronchial reactivity. Dose-response relationships were analysed by four methods: (1) PD20 by the conventional method of interpolating the dose on a logarithmic scale between the last two measurements of FEV1; (2) PD20 (with allowance for extrapolation), estimated by fitting an exponential curve to the dose-response data; (3) the linear regression slope between dose and FEV1 when significant; (4) the dose-response slope obtained in all subjects as the % change in FEV1 from baseline in response to total dose. When each of these measures was related to symptoms, diagnosis, and treatment of asthma, all differentiated between 'asthmatic' and 'non-asthmatic' subjects. The dose-response slope (method 4) had the advantages of simplicity and no censored data, and was shown to be clinically relevant. It is suggested that the dose-response slope should be used for the analysis of bronchial reactivity in epidemiological studies.

Uvulopalatopharyngoplasty was performed in 18 consecutive patients (15 men and three women; mean ± standard deviation [SD] age, 46.3 ± 7.5 years) who presented for the treatment of heavy habitual snoring. No attempt was made to select patients who were ideal anatomically for palatal modification. The loudness of snoring was measured during sleep by integrating the output of a calibrated microphone. An assessment before operation showed that nine patients had obstructive sleep apnoea; four patients had an apnoea index of greater than or equal to 25 apnoeas per hour. The patients were overweight and consumed, on average, 39 g of alcohol per day, but these variables did not change after the operation. The postoperative assessment was performed 138 ± 44 days after uvulopalatopharyngoplasty. Fourteen patients showed a reduction in the loudness of their snoring, although snoring was abolished in one patient only (average snoring loudness in arbitrary units/min of sleep, 2.8 ± 2.1 before operation compared with 1.4 ± 1.5 units/min of sleep after the operation; P < 0.05. The loudest snore in arbitrary units measured 7.1 ± 3.3 units compared with 4.8 ± 3.3 units, respectively; P < 0.05). The percentage of the sleep time that was spent at an arterial oxygen saturation of less than 90% was reduced after uvulopalatopharyngoplasty (28% ± 32% of total sleep time compared with 17% ± 24% of total sleep time, respectively; P < 0.05). There was no change in the apnoea index. The diastolic blood pressure was lower at the postoperative assessment (94 ± 11 mmHg compared with 87 ± 8 mmHg; P < 0.05); six of 10 subjects whose diastolic blood pressure were greater than or equal to 95 mmHg before the operation had a diastolic blood pressure of less than 95 mmHg after uvulopalatopharyngoplasty (P < 0.02). Computed tomographic scans showed an increase in the upper airway cross-sectional area at 3 cm and 4 cm above the hyoid bone after uvulopalatopharyngoplasty (P < 0.05). We conclude that uvulopalatopharyngoplasty is an effective treatment for habitual, heavy snoring in many patients, but it is not the treatment of choice for patients with clinically-significant obstructive sleep apnoea.

The evidence concerning a relationship between work in the aluminum industry and lung disease has been reviewed using epidemiologic criteria. Adequate data on environmental exposure are rarely presented. Case series on aluminum potroom workers over the past 50 years have identified an asthmalike syndrome that appears to be due to an irritant rather than an allergic mechanism. These studies have been supported by evidence of within shift variability of measures of lung function. However, to date, there is inadequate evidence to resolve the question of whether potroom exposure initiates asthma or merely precipitates asthmalike symptoms in a predisposed individual. Cross-sectional studies have demonstrated evidence of reduced lung function, consistent with chronic airflow limitation, in exposed aluminum smelter workers compared to unexposed control subjects. Cigarette smoking, the major potential confounding variable, has been measured and accounted for in multivariate analyses. To date, evidence is lacking from longitudinal studies about the development of disabling chronic obstructive lung disease. Exposure to coal tar pitch volatiles in the production and consumption of anodes has biologic plausibility for an association of lung cancer with work in an aluminum smelter. Although retrospective mortality studies have failed to account for the probable high prevalence of smoking in blue collar workers, the relative risk of lung cancer is very low if present at all. Pulmonary fibrosis has not been shown to be a significant problem in aluminum smelter workers. Future research in the aluminum industry needs to concentrate on longitudinal studies, preferably with an inception cohort for the investigation of potroom asthma.

A technique, suitable for clinical practice, has been developed to measure quantitatively and separately the effects of hypercapnia on the central and peripheral chemoreceptors, and hypoxia on the peripheral chemoreceptors of a human subject. The technique uses a model to account for the dynamics of CO2 transport in the brain and is based on current concepts of the chemoreceptor system and makes a minimum of assumptions. The method was tested in one subject and there was evidence for hysteresis in the response to hypoxia and short-term adaptation in the response to hypercapnia of the chemoreceptor controller. © 1986.

A trial with a trivalent influenza subunit vaccine prepared with sodium deoxycholate was carried out in 88 volunteers between May and November 1981. Each haemagglutinin antigen was present at 7 µg per dose. Fourfold or greater haemagglutination inhibition antibody (HI) responses to the H1N1 virus A/Brazil/11/78 occurred in 70% of the volunteers following a single dose. For the H3N2 virus A/Bangkok/1/79 and B/Singapore/222/79 these figures were 52 and 11%, respectively. No increase in the antibody titre was noted to any of the antigens following a second vaccination dose. Antibody levels remained relatively constant six months after vaccination. A response to B/Singapore/222/79, comparable with the HI response for the influenza A antigens, was noted when serum titres were estimated by a plaque reduction procedure. No neuraminidase inhibition antibody could be detected in response to either A/Brazil/11/78 or A/Bangkok/1/79. No reactions specifically attributable to the vaccine occurred after either injection. A lower HI response to A/Brazil/11/78 was noted in volunteers 52 years of age and older, who also showed less evidence of earlier priming to this virus. Levels of nasal wash neutralizing antibodies to A/Brazil/11/78 were proportional to those detected in sera by HI tests, but were present in smaller amounts. © 1984.

Twenty-two deaths from asthma are examined. The majority of patients had experienced the asthma attack for some time; in spite of this, 73 per cent of the deaths occurred outside hospital. Several of these may have been preventable.

Nine adult patients with obstructive sleep apnea syndrome were administered medroxyprogesterone acetate, 60 to 120 mg/day, and the effect of medroxyprogesterone on clinical symptoms and obstructive apneas during sleep was assessed. Four patients responded with resolution of daytime sleepiness, disappearance of pedal edema, and a decrease in the number of obstructive apneas during sleep. Cessation of therapy led to a return of daytime sleepiness in three and an increase in obstructive apneas in all four subjects. Two responders experienced side effects of alopecia or decreased libido. Before medroxyprogesterone therapy, responders were distinguished from nonresponders only by the presence of a significantly lower resting arterial oxygen tension during wakefulness. We characterize a subgroup of patients who benefit from medroxyprogesterone therapy by reducing obstructive apneas during sleep. © 1981, American Medical Association. All rights reserved.

Nine adult patients with obstructive sleep apnea syndrome were administered medroxyprogesterone acetate, 60 to 120 mg/day, and the effect of medroxyprogesterone on clinical symptoms and obstructive apneas during sleep was assessed. Four patients responded with resolution of daytime sleepiness, disappearance of pedal edema, and a decrease in the number of obstructive apneas during sleep. Cessation of therapy led to a return of daytime sleepiness in three and an increase in obstructive apneas in all four subjects. Two responders experienced side effects of alopecia or decreased libido. Before medroxyprogesterone therapy, responders were distinguished from nonresponders only by the presence of a significantly lower resting arterial oxygen tension during wakefulness. We characterize a subgroup of patients who benefit from medroxyprogesterone therapy by reducing obstructive apneas during sleep.

Summary: A test of the ventilatory response to hypoxia and hypercapnia for clinical use. M. J. Hensley and D. J. C. Read, Aust. N.Z. J. Med., 1977, 7, pp. 362¿367. A new technique is described for testing the ventilatory response to hypoxia and to hypercapnia The test consists of interposing 15¿20 seconds of hypoxia in 3¿4 minutes of rebreathing 7% CO2; the hypoxia is induced by taking three to five breaths from a bag containing N2, and CO2 at an identical level. When required, hypoxic tests can be performed at several different PCO2 levels to define the interaction of hypoxic and hypercapnic stimuli In eight healthy subjects, 29 hypoxic tests were performed, at an average PCO2 of 58 mm Hg (range 53¿64). The correlation between ventilatory increments and 02-desaturation was significant in 27 of the 29 tests (r = 0.81-0.99). At the minimum 02-saturation (average 85%; range 75¿91%) there was a statistically significant ventilatory response to hypoxia in all 29 tests (average +60%; range +14 to +141%). At 90% O2-saturation, the average increment of ventilation was +48% This method has important theoretical and practical advantages for clinical studies: (i) the test involves only 15¿20 seconds of hypoxia; (ii) since the hypoxic drive to breathing is greatly enhanced by hypercapnia only a mild degree of hypoxaemia is necessary to obtain a clearly defined response; (iii) the augmented ventilation, produced by rebreathing, allows N2 to be rapidly introduced into the lungs without the need for voluntarily imposed deep breathing; (iv) the elevated PCO2 increases cerebral blood flow and minimises brain tissue hypoxia. (v) Since rebreathing 7% CO2 greatly reduces mixed venous-arterial and cerebral tissue-arterial PCO2 differences, the cerebral tissue PCO2 and CO2 stimulus are virtually unaffected by both ventilatory and cerebral blood flow responses in this test Copyright © 1977, Wiley Blackwell. All rights reserved

Summary: Intermittent obstruction of the upper airway during sleep causing profound hypoxaemia. A neglected mechanism exacerbating chronic respiratory failure. An obese patient with a ten year history of respiratory failure presented with insomnia and marked daytime somnolence. Respiratory failure had been attributed to obesity, respiratory centre insensitivity to carbon dioxide, and to diffuse airways obstruction. To investigate the possible role of episodic apnoea with frequent nocturnal arousals, continuous recordings were obtained during sleep of arterial oxygen saturation, oesophageal pressure and the motions of the rib-cage and abdomen/diaphragm. Repeated episodes of hypoventilation and profound hypoxaemia were found which were due to intermittent obstruction of the upper airway rather than to cessation of breathing efforts. During the episodes of hypoxaemia, values of arterial 02 tension fell to as low as 24 mmHg. Episodic hypoxaemia was relieved but not abolished, by the use of a collar, designed to hold the mandible forward. Previous reports indicated that recognition of intermittent obstruction of the upper airway during sleep and treatment by a permanent tracheostomy, resulted in a significant long-term improvement of pulmonary and cardiac function and relief of insomnia and day-time somnolence. When tracheostomy is inadvisable, as in the present patient, it is hoped that similar long-term benefits will result from a supportive collar. Copyright © 1976, Wiley Blackwell. All rights reserved

ABPA is an important complication of chronic asthma resulting from hypersensitivity to the fungus Aspergillus Fumigatus ( AF}. ABPA is characterised by an intense immune response with increased use of oral steroids and potentially progressive lung disease. The aim of this study was to determine if treatment of subjects with ABPA with the antifungal agent Itraconazole (Itz) reduced airway and systemic inflammation. Methods: A randomised double blind placebo controlled trial was performed in stable subjects with ABPA (n=29). Subjects with cystic fibrosis ere excluded. The diagnosis of ABPA was based upon; the presence of asthma, IgE sensitisation to Af. a total serum IgE of lOOOIl'/mL or greater and serum IgG to Af or central bronchiectasis on CT scan. Subjects received Itz 400mg per day (n=15) or placebo (n=14) for 16 weeks. All subjects were reviewed monthly with history, spirometry. sputum induction to measure airway inflammation, serum total IgE and IgG to Af and blood eosinophils. Results: Subjects receiving Itz had a greater reduction in sputum eosinophils from baseline (median fall of 94.5%) compared to placebo (45.4%. p<0.01 ). Those on Itz had a fall in sputum total cell count from baseline (43.9%) compared to a rise in those on placebo (rise 10%. p=0.049). Subjects that received Itz also had a reduction in systemic immune activation; there was a fall in serum IgE (3IOIU/mL) compared to placebo (rise ISIU-'mL, p<0.01) and a fall in IgG to Af(15.4IU/mL) compared to placebo (rise 3.7IU-mL, p=0.03). Conclusion: Treatment of subjects with stable ABPA with Itz 400mg daily reduces eosinophilic airway inflammation along with measures of systemic immune activation. These results imply that Itz is a potential adjunctive treatment for ABPA and this should be further investigated with larger studies of lone term clinical efficacv.