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BACKGROUND AND OBJECTIVE Sleep-disordered breathing (SDB) has been reported as highly prevalent in idiopathic pulmonary fibrosis (IPF) and other interstitial lung disease (ILD) populations. Nocturnal oxygen desaturation (NOD), or the total sleep time spent with SpoO2 < 90% (TST

Exercise limitation is a common feature in idiopathic interstitial pneumonia (IIP). There are multiple contributing pathophysiological mechanisms, including ventilatory mechanical limitation, impaired gas exchange, pulmonary vascular insufficiency and peripheral muscle dysfunction. Progressive exertional dyspnoea and functional incapacity impact significantly on quality of life. Exercise-induced desaturation is frequently observed and is predictive of poorer outcomes. Tests to assess the cardiorespiratory system under stress (e.g. cardiopulmonary exercise testing and the 6-min walk test) can provide important physiologic and prognostic information as adjuncts to resting measurements of lung function. Despite many advances in understanding disease mechanisms, therapies to improve exercise capacity, symptom burden and quality of life are lacking. Exercise training and supplemental oxygen are two potential interventions that require closer evaluation in patients with IIP.

Background Pulmonary arterial hypertension (PAH) is an increasingly recognised serious illness with insidious onset, delayed diagnosis, complex diagnostic algorithms and poor prognosis, but with recently available effective treatments. Aims To efficiently diagnose and to offer treatment for PAH, we established a multidisciplinary service in 2005, where patients attend a clinic staffed by specialists in cardiology, respiratory medicine, rheumatology and immunology in a tertiary referral hospital setting. Methods We studied the first 200 patients referred. Serology, echocardiography, lung function tests, high-resolution computed tomography, World Health Organisation Class determination and 6-min walk tests and/or right heart catheterisation were performed, as clinically indicated. Results Of the 200 patients seen, 66 had confirmed pulmonary hypertension (mean pulmonary artery pressure > 25 mmHg) diagnosed on echocardiography ± right heart catheterisation. Of these patients, 58 had catheter-proven PAH (mean pulmonary artery pressure > 25 mmHg with mean wedge pressure < 15 mmHg). Underlying diagnoses for the confirmed PAH patients were idiopathic (32), scleroderma-associated (14), other connective tissue disease (4) and associated with congenital heart disease (8). Patients with confirmed PAH were commenced on PAH-specific therapy – initially bosentan in the majority but sildenafil, and iloprost were occasionally used initially for patient-specific reasons. Median time from when the patient first called the clinic to prescription of therapy was 16 days (interquartile range; 0–31 days). All surviving patients with PAH have attended for regular 6-monthly follow-up visits with a 100% retention rate up to 4 years. Conclusion A multidisciplinary clinic can provide efficient diagnosis and rapid triage to PAH-specific therapy, if appropriate. Retention rates remain high, at follow up.

The regional pattern and extent of airway closure measured by three-dimensional ventilation imaging may relate to airway hyperresponsiveness (AHR) and peripheral airways disease in asthmatic subjects. We hypothesized that asthmatic airways are predisposed to closure during bronchoconstriction in the presence of ventilation heterogeneity and AHR. Fourteen asthmatic subjects (6 women) underwent combined ventilation single photon emission computed tomography/computed tomography scans before and after methacholine challenge. Regional airway closure was determined by complete loss of ventilation following methacholine challenge. Peripheral airway disease was measured by multiple-breath nitrogen washout from which Scond (index of peripheral conductive airway abnormality) was derived. Relationships between airway closure and lung function were examined by multiple-linear regression. Forced expiratory volume in 1 s was 87.5 ± 15.8% predicted, and seven subjects had AHR. Methacholine challenge decreased forced expiratory volume in 1 s by 23 ± 5% and increased nonventilated volume from 16 ± 4 to 29 ± 13% of computed tomography lung volume. The increase in airway closure measured by nonventilated volume correlated independently with both Scond (partial R2 = 0.22) and with AHR (partial R2 = 0.38). The extent of airway closure induced by methacholine inhalation in asthmatic subjects is greater with increasing peripheral airways disease, as measured by ventilation heterogeneity, and with worse AHR.

Background: Globally, cardiovascular disease (CVD) is the leading cause of death. Beta-blocker medications have well-established survival benefit for myocardial infarction and heart failure. However, CVD frequently coexists with chronic obstructive airways disease (COPD), a disease in which beta-blockers are traditionally avoided. We sought to investigate the adverse respiratory effects associated with long term beta-blocker treatment in patients with cardiac disease, and presumed high risk of COPD. Methods: In this prospective cohort study, patients admitted with acute cardiac disease were recruited from the cardiology unit of a tertiary referral hospital. The treating cardiologist determined beta-blocker treatment, independent of the study. Repeated measures of spirometry and respiratory symptom scores were assessed over 12 months. Respiratory exacerbations, cardiac events and survival were recorded over six years. Outcomes were compared according to beta-blocker exposure. Results: Sixty-four subjects participated, 30 of whom received beta-blockers. Beta-blockers did not adversely affect spirometry, respiratory symptoms or survival. However, considering two categories of respiratory exacerbations (symptom-based versus treated) subjects taking beta-blockers accumulated increased annual risk (RR 1.30, 95% CI 1.11 - 1.53, P = 0.001 and RR 1.37, 95% CI 1.09 - 1.72, P = 0.008) and concluded with overall increased risk (RR 3.67, 95% CI 1.65 - 8.18, P = 0.001 and RR 4.03, 95% CI 1.26 - 12.9, p = 0.019), when compared with the group not taking beta-blockers. Conclusions: Long term beta-blocker treatment did not adversely affect lung function, respiratory symptom scores or survival, but was associated with increased risk of respiratory exacerbations.

Summary Background Palliative oxygen therapy is widely used for treatment of dyspnoea in individuals with life-limiting illness who are ineligible for long-term oxygen therapy. We assessed the effectiveness of oxygen compared with room air delivered by nasal cannula for relief of breathlessness in this population of patients. Methods Adults from outpatient clinics at nine sites in Australia, the USA, and the UK were eligible for enrolment in this double-blind, randomised controlled trial if they had life-limiting illness, refractory dyspnoea, and partial pressure of oxygen in arterial blood (PaO 2 ) more than 7·3 kPa. Participants were randomly assigned in a 1:1 ratio by a central computer-generated system to receive oxygen or room air via a concentrator through a nasal cannula at 2 L per min for 7 days. Participants were instructed to use the concentrator for at least 15 h per day. The randomisation sequence was stratified by baseline PaO 2 with balanced blocks of four patients. The primary outcome measure was breathlessness (0–10 numerical rating scale [NRS]), measured twice a day (morning and evening). All randomised patients who completed an assessment were included in the primary analysis for that data point (no data were imputed). This study is registered, numbers NCT00327873 and ISRCTN67448752. Findings 239 participants were randomly assigned to treatment (oxygen, n=120; room air, n=119). 112 (93%) patients assigned to receive oxygen and 99 (83%) assigned to receive room air completed all 7 days of assessments. From baseline to day 6, mean morning breathlessness changed by −0·9 points (95% CI −1·3 to −0·5) in patients assigned to receive oxygen and by −0·7 points (−1·2 to −0·2) in patients assigned to receive room air (p=0·504). Mean evening breathlessness changed by −0·3 points (−0·7 to 0·1) in the oxygen group and by −0·5 (−0·9 to −0·1) in the room air group (p=0·554). The frequency of side-effects did not differ between groups. Extreme drowsiness was reported by 12 (10%) of 116 patients assigned to receive oxygen compared with 14 (13%) of 108 patients assigned to receive room air. Two (2%) patients in the oxygen group reported extreme symptoms of nasal irritation compared with seven (6%) in the room air group. One patient reported an extremely troublesome nose bleed (oxygen group). Interpretation Since oxygen delivered by a nasal cannula provides no additional symptomatic benefit for relief of refractory dyspnoea in patients with life-limiting illness compared with room air, less burdensome strategies should be considered after brief assessment of the effect of oxygen therapy on the individual patient. Funding US National Institutes of Health, Australian National Health and Medical Research Council, Duke Institute for Care at the End of Life, and Doris Duke Charitable Foundation.

This document attempts to provide a broad consensus statement about common practice in respiratory function testing and the use of its results in assessing respiratory disease and disability. It is written for respiratory and general clinicians. General principles only are provided and the source documents are referenced but detail is not exhaustive and technically the document does not attempt to provide best practice guidelines. It is meant to reflect usual practice and in some individual patients use of respiratory function tests outside these guidelines may clearly be appropriate in particular clinical circumstances. General statements about quality assurance and cost benefit will be given at the end of the document but for each individual test there are sections on description, indications, interpretation, normal values, specific quality assurance and cost benefit. The scope of the document will cover tests of mechanical function, gas exchange and exercise assessment.

Patients with chronic obstructive pulmonary disease and a stable daytime PaO2 of 55 mmHg (7.3kPa) live longer and have a better quality of life if provided with long-term continuous oxygen therapy. • It is reasonable to offer continuous oxygen therapy also to patients with other lung diseases that cause chronic hypoxaemia. • Indications for supplemental oxygen therapy during exercise (ambulatory oxygen therapy) and sleep (nocturnal oxygen MJA 2005; 182: 621-626 therapy) are less clear. This position statement is a consensus statement based on evidence from English-language publications up to 2004 obtained by searching MEDLINE and EMBASE with the keywords domiciliary, home, long term and oxygen. We retrieved and reviewed 417 articles. We prepared the position statement, which was then reviewed and revised in consultation with the Clinical Care and Resources Subcommittee and the executive of the Thoracic Society of Australia and New Zealand (TSANZ). It was endorsed in December 2004 by the executive of the TSANZ. We made minor modifications after independent peer review via the Medical Journal of Australia. These changes were once again endorsed by the Clinical Care and Resources Subcommittee of the TSANZ. This is an update of the position statement published in the Journal in 1998 1 and has a currency of 5 years from the date of publication (unless superseded). We used the National Health and Medical Research Council's four levels of evidence (Levels I-IV, designated here E1-E4). 2

Inhaled mannitol increases mucus clearance in patients with bronchiectasis by an unclear mechanism. The effect of mannitol on lung function, health status and sputum properties was investigated.Nine patients with bronchiectasis inhaled 400 mg of mannitol once daily for 12 days. Health status was assessed using the St George's Respiratory Questionnaire (SGRQ). Sputum was analysed for viscosity, elasticity, spinnability, surface tension, contact angle, solids, mucociliary transportability (MCTR) on a frog palate, and cough transportability (CTR) on a simulated cough machine.Lung function was unchanged with treatment (baseline FEV1 82.0 +/- 16.2%) apart from an improvement in FEF from 85.4 +/- 13% (baseline) to 90.7 +/- 14.4% (P0.05; 12th treatment; visit 7). The total SGRQ score (mean +/- SD) of 49.3 +/- 13.8 at baseline, decreased by 12.4 +/- 10.2 (P0.01; visit 7) and 10.1 +/- 9.4 units (P0.02) 6-10 days after treatment cessation. The baseline subscores for symptoms (72.9 +/- 11.8), activity (44.7 +/- 20.9) and impact (44.4 +/- 14.3) were reduced by 0.8 +/- 9.1 (P0.7), 8.4 +/- 16.0 (P0.1) and 19.2 +/- 13.7 (P0.005) units, respectively (visit 7). Mannitol reduced the baseline (mean +/- SE) surface tension from 94.5 +/- 1.4 to 84.7 +/- 2.1 mN/m (P0.0001), contact angle from 51.1 +/- 2.8 to 33.2 +/- 2.4 degrees (P0.0001), spinnability from 11.6 +/- 0.4 to 10.0 +/- 0.2 mm (P0.005), and solids from 5.7 +/- 0.4 to 4.3 +/- 0.7% (P0.02), acutely (visit 7). Viscosity, elasticity and MCTR did not change significantly, while CTR was increased from 25.8 +/- 1.0 to 34.1 +/- 2.7 mm (P0.003).Mannitol significantly improved the health status over 12 days and this improvement was maintained for 6-10 days after cessation of treatment. In addition, mannitol reduced the tenacity, increased the hydration of mucus acutely and improved cough clearability in patients with bronchiectasis.

The absence of a maximal dose-response plateau as well as gas trapping and increases in closing capacity (CC) suggest that increased airway closure is an important mechanical abnormality of asthmatic airways. We compared the extent and distribution of airway closure in 13 normal and in 23 asthmatic subjects. Airway closure (LVclosed) was measured with single-photon emission computed tomography (SPECT) and an inhaled Technegas bolus as the percentage of lung volume without Technegas (LVtrans), and with CC, using nitrogen washout. LVclosed was compared in the apical, middle and lower zones, each being of equal vertical height. Values of mean LVclosed +/- 95% confidence interval (CI) were similar in normal (30 +/- 6.0% LVtrans) and asthmatic subjects (30 +/- 7.8% LVtrans). In normal subjects, LVclosed correlated with both age (r = 0.89, p < 0. 01) and CC (r = 0.86, p < 0.01), was more extensive in the lower zone (58 +/- 18.8% LVtrans, p < 0.01) than in the middle and upper zones (17 +/- 8.7% and 26 +/- 8.2 LVtrans, respectively), and increased with age in both the middle and lower zones (r = 0.94 and r = 0.90, respectively, p < 0.01). In asthmatic subjects, LVclosed did not correlate with age; was greatest in the lower zone, intermediate in the middle zone, and lowest in the apical zone (59 +/- 13.2%, 22 +/- 5.8%, and 12 +/- 4.4% LVtrans, respectively, p < 0. 01); and correlated weakly with age in the middle zone only (r = 0. 46, p < 0.05). We conclude that there is a predictable pattern of airway closure in normal subjects and that it is primarily influenced by pulmonary elastic recoil. This pattern is lost in asthmatic subjects. This may be explained by an increased range of closing pressures and a patchy distribution of airway closure, probably secondary to allergic inflammation.

To assess if exercise capacity and resting stroke volume are different in tetralogy of Fallot (TOF) repair survivors with indexed RV (right ventricle) end-diastolic volume (RVEDVi) more versus less than 150 ml/m(2), a currently suggested threshold for pulmonary valve replacement (PVR).Cross-sectional study.Single-centre adult congenital heart disease unit.55 consecutively eligible patients with repaired TOF (age at repair 2.3±1.9 years; age at evaluation 26.2±8.8 years; NYHA Class I or II).Cardiovascular MRI (1.5T) and cardiopulmonary exercise test.Biventricular volumes and function; exercise capacity.20 patients had RVEDVi below, and 35 had RVEDVi above 150 ml/m(2), at time of referral. In the150 ml/m(2) group, fractional pulmonary regurgitation was higher (41±8 vs 31±8%, p0.001). Although RV ejection fraction (EF) was lower (47±7 vs 54±6%, p=0.007), indexed RV stroke volume was higher (87±14 vs 64±10 ml/m(2), p0.001) in the150 ml/m(2) group. There were no significant differences in LVEF, indexed LV stroke volume or exercise capacity (% predicted peak work: 90±17 vs 89±11% and; % predicted VO(2) peak: 84±17 vs 87±12%).Exercise capacity and stroke volume are maintained with RVEDVi above compared with below a commonly used cut-off for PVR surgery. Optimal timing for PVR, thus, remains unclear.

Background Studies using the multiple inert gas elimination technique (MIGET) to characterise the mechanisms of impaired gas exchange in CF, provide conflicting results on the importance of ventilation–perfusion ( V A / Q ) inequality over shunt. We hypothesise that the mechanisms of gas exchange abnormality have changed with changing CF management over the last two decades. Methods Detailed gas exchange was evaluated by MIGET with venous sampling in stable patients, age>20 years, FEV 1 % predicted ≤50. Results Fifteen (14 male) subjects were studied with a mean±SD age 28.1±8.4 years, FEV 1 % 32.6±10.3, TLC% 111.5±12.9, PaO 2 9.3±1.3 kPa, (69.5±9.6 mm Hg), and PaCO 2 6.2±0.7 kPa, (45.9±5.3 mm Hg). The predominant gas exchange abnormality was V A / Q inequality with a log SD of the distributions of perfusion 0.91±0.30 and of ventilation 0.60±0.14. Unimodal distributions were seen in nine subjects, a low V A / Q mode in five and one subject had a bimodal distribution, mean intrapulmonary shunt was negligible. Conclusions Subjects had a lower FEV 1 % by comparison with previously published studies and demonstrated severe V A / Q inequality and negligible shunt. This suggests a low degree of complete obstruction of airways in adults with CF and severe stable pulmonary disease. The primary mechanism of hypoxaemia in CF subjects reaching adulthood today appears to have changed with modern management over the last two decades.

Bronchiectasis is characterised by hypersecretion and impaired clearance of mucus. A 400-mg dose of inhaled mannitol improves mucus clearance however, the effect of other doses is unknown. A total of 14 patients, aged 63.3+/-5.7 yrs, were studied on five visits. Mucus clearance at baseline and with mannitol (160, 320 and 480 mg) was measured using technetium-99m-sulphur colloid and imaging with a gamma camera over 45 min, followed by a further 30 min involving 100 voluntary coughs. A control study assessed the effect of cough provoked by mannitol during the intervention. Whole right lung clearance over 45 min was 4.7+/-1.2 and 10.6+/-2.6% on baseline and control days, respectively, and increased to 16.7+/-4.2, 22.8+/-4.2 and 31+/-4.7% with 160, 320 and 480 mg mannitol, respectively. Clearance over 45 min with 480 mg mannitol was greater than clearance with 320 and 160 mg. Total clearance over 75 min, after mannitol administration and voluntary coughs, was 36.1+/-5.5, 40.9+/-5.6 and 46.0+/-5.2% with 160, 320 and 480 mg mannitol, respectively, all significantly different from baseline (24.1+/-6.0%) and control (13.1+/-3.0%). Total clearance over 75 min with 480 mg mannitol was greater compared with 160 mg. In conclusion, mucus clearance increases with increasing doses of mannitol and can be further increased by cough in patients with bronchiectasis.

This study evaluates the physiological responses to giant bullectomy. A 42-year-old female with bilateral giant bullae presented with dyspnoea and exercise limitation. At baseline and 3 months after bullectomy she had tests of lung function; exercise capacity via a symptom-limited cycle test and a 6-min walk test (6MWT). Quality of life (QoL) and gas exchange using the multiple inert gas elimination technique (MIGET) were also assessed. There were significant improvements in pulmonary function following surgery with the FEF25–75% predicted increasing from 16 to 96. The 6MWT increased by 10% and the peak leg work capacity by 48%. A MIGET measure of the distribution of perfusion (Log SDQ) fell from 0.52 to 0.36. There was also radiological improvement in hyperinflation and diaphragmatic configuration. The QoL total score decreased from 56 to 25. This patient demonstrated significant improvements in exercise tolerance, gas exchange and QoL following bullectomy.

To investigate the acute effect of mannitol on the clearance of mucus, and (1) the 24-h mucus retention, and (2) the mucus clearance rate and lung function 24 h after inhalation of a single dose of mannitol.Clearance of mucus was measured on 3 consecutive days using (99m)Tc-sulfur colloid radioaerosol and a gamma camera.Mannitol, 330 +/- 68 mg (mean+/- SD), was inhaled using a dry powder inhaler only on day 2.Eight patients with bronchiectasis (age range, 29 to 70 years).On each day, lung images were collected over 2 h and at 24 h. Key findings of the study are as follows: (1) the 24-h retention of mucus was reduced the day after mannitol had been inhaled, compared to the day without mannitol (day 1) in the whole right lung (57.6 +/- 6.2% vs 68.1 +/- 5.9%), central (47.5 +/- 6.7% vs 56.9 +/- 6.5%), intermediate (61.7 +/- 5.6% vs 73.8 +/- 5.5%), and peripheral regions (70.9 +/- 4.3% vs 86.6 +/- 4.6%)(p0.02); and (2) mannitol helped patients clear mucus within 2 h that might otherwise take up to 24 h, from the whole right lung and defined regions. However, clearance over 60 min measured 24 h after mannitol inhalation was not significantly different to baseline clearance without mannitol (8.7 +/- 1.9% on day 1 vs 9.7 +/- 3.7% 24 h after mannitol; p0.8). The patients maintained the same lung function the day before and after mannitol had been inhaled: FEV(1) (percent predicted), 79 +/- 5 on day 1 vs 80 +/- 5 on day 3; and forced expiratory flow, midexpiratory phase (percent predicted), 50 +/- 6 on day 1 vs 51 +/- 6 on day 3; p0.6).Mannitol inhalation acutely increases clearance of mucus, and this effect extends beyond the acute study period, resulting in decreased mucus retention at 24 h.

An elderly woman presented with unexplained, intermittent hypoxaemia unrelated to posture. Subsequent investigations revealed intermittent and variable right-to-left interatrial shunting through a patent foramen ovale in the presence of normal pulmonary arterial and intracardiac pressures, caused by right atrial compression from a horizontal, elongated ascending aorta. Surgical closure of the foramen resulted in marked clinical improvement.

To test the hypothesis that diffusion-limitation for oxygen is due to abnormal vascular dilatation and significantly contributes to the arterial hypoxaemia of liver cirrhosis requires an experimental approach that detects both diffusion-limitation for oxygen and the presence of abnormal dilatation of pulmonary vessels exposed to alveolar gas. We therefore studied the gas exchange of a 64 year old man with alcoholic liver cirrhosis and severe resting arterial hypoxaemia (arterial oxygen tension (Pa,O2) 7.5 kPa) whilst breathing air and 100% O2 using conventional blood gas (CBG) analysis, the multiple inert gas elimination technique (MIGET) and whole body scintigraphy (WBS) following the i.v. administration of radiolabelled boli of macroaggregates with a minimum diameter of 15 microM. During air breathing, there was a consistently positive difference between the arterial oxygen tension predicted by MIGET and that actually measured (P-M Pa,O2, average 0.9 kPa). During O2 breathing, P-M Pa,O2 became negative, (average -12.2 kPa), and shunt estimated by the O2 method (% of Q') was consistently less than that measured by MIGET. Whereas both O2 method and MIGET estimates of shunt never exceeded 25%, the WBS shunt was 40%, indicating that a substantial fraction of cardiac output flowed through abnormally dilated pulmonary vessels, some of which were exposed to alveolar gas and, hence, participated in gas exchange. Although our observations pertain to one subject, we believe they provide the most convincing in vivo evidence to date that abnormal dilatation of interalveolar vessels may, per se, result in a significant diffusion impairment for O2. Furthermore, in view of the consistently negative P-M Pa,O2 observed during oxygen breathing, we speculate that such abnormal vascular dilatation may also have produced a significant diffusive impairment of one or more of the less soluble inert gases used in the MIGET analysis.

is a timely reminder of the importance of avoiding the induction of hyperoxic hypercapnia in patients with acute-on-chronic respiratory failure. The complica-tion of acute hypercapnic respiratory failure precipitated by giving oxygen has long been recognised; most resident medical and nursing staff are aware of this problem. The natural intervention in patients presenting with acute-on-chronic respiratory failure is to relieve any hypoxia with supplemental oxygen, but this can be associated with carbon dioxide retention, narcosis, respiratory acidosis, and death. That the use of controlled oxygen flow rates could avoid this complication (and the need, in those days, for tracheostomy and invasive ventilation) was first recognised in the 1940s and 1950s.