A multicentre, open-label, randomised controlled trial of NIV plus long-term oxygen therapy (LTOT) versus LTOT alone was performed in four Australian University Hospital sleep/respiratory medicine departments in patients with severe stable smoking-related COPD (forced expiratory volume in 1 s (FEV_1.0) <1.5 litres or <50% predicted and ratio of FEV_1.0 to forced vital capacity (FVC) <60% with awake arterial carbon dioxide tension (Paco₂) >46 mm Hg and on LTOT for at least 3 months) and age <80 years. Patients with sleep apnoea (apnoea-hypopnoea index >20/h) or morbid obesity (body mass index >40) were excluded. Outcome measures were survival, spirometry, arterial blood gases, polysomnography, general and disease-specific quality of life and mood.

144 patients were randomised (72 to NIV + LTOT and 72 to LTOT alone). NIV improved sleep quality and sleep-related hypercapnia acutely, and patients complied well with therapy (mean (SD) nightly use 4.5 (3.2) h). Compared with LTOT alone, NIV (mean follow-up 2.21 years, range 0.01–5.59) showed an improvement in survival with the adjusted but not the unadjusted Cox model (adjusted hazard ratio (HR) 0.63, 95% CI 0.40 to 0.99, p = 0.045; unadjusted HR 0.82, 95% CI 0.53 to 1.25, p = NS). FEV_1.0 and Paco₂ measured at 6 and 12 months were not different between groups. Patients assigned to NIV + LTOT had reduced general and mental health and vigour.

Nocturnal NIV in stable oxygen-dependent patients with hypercapnic COPD may improve survival, but this appears to be at the cost of worsening quality of life.

ACTRN12605000205639

The THIN database was searched for patients with COPD. Vaccination status against Pneumococcus and the annual influenza vaccination status were determined. Mortality rates were calculated in the periods December to March and April to November. Relative risks for the effect of vaccination on all-cause mortality were estimated by Poisson regression, adjusting for age, sex, year and serious co-morbidities.

177 120 patients with COPD (mean age 65 years) were identified, with a mean follow-up of 6.8 years between 1988 and 2006. Vaccination rates against influenza rose from <30% before 1995 to >70% in 2005 in patients aged 60 years or more. The cumulative vaccination rate against pneumonia rose from almost zero to 70% in patients aged 70 years or more over the same period. For all-cause mortality the adjusted relative risks associated with influenza vaccination were 0.59 (95% CI 0.57 to 0.61) during the influenza season and 0.97 (95% CI 0.94 to 1.00) outside the season in patients not vaccinated against pneumonia, and 0.30 (95% CI 0.28 to 0.32) and 0.98 (95% CI 0.96 to 1.11), respectively, in patients vaccinated against pneumonia. The relative risk associated with pneumococcal vaccination was >1 at all times of the year.

Influenza but not pneumococcal vaccination was associated with a reduced risk of all-cause mortality in COPD.

All 2107 children aged 9–14 years from 40 schools in Rome in 2000–1 were included in a cross-sectional survey. Respiratory symptoms were assessed on 1760 children by parental questionnaires (response rate 83.5%). Allergic sensitisation was measured by skin prick tests and lung function was measured by spirometry on 1359 children (77.2%). Three indicators of traffic-related air pollution exposure were assessed: self-reported heavy traffic outside the child’s home; the measured distance between the child’s home and busy roads; and the residential nitrogen dioxide (NO₂) levels estimated by a land use regression model (R² = 0.69).

There was a strong association between estimated NO₂ exposure per 10 µg/m³ and lung function, especially expiratory flows, in linear regression models adjusted for age, gender, height and weight: –0.62% (95% CI –1.05 to –0.19) for forced expiratory volume in 1 s as a percentage of forced vital capacity, –62 ml/s (95% CI –102 to –21) for forced expiratory flow between 25% and 75% of forced vital capacity and –85 ml/s (95% CI –135 to –35) for peak expiratory flow. The other two exposure indicators showed similar but weaker associations. The associations appeared stronger in girls, older children, in children of high socioeconomic status and in those exposed to parental smoking. Although lifetime asthma was not an effect modifier, there was a suggestion of a larger effect on lung function in subjects with a positive prick test. Multiple logistic regression models did not suggest a consistent association between traffic-related air pollution exposure and prevalence of respiratory symptoms or allergic sensitisation.

The results of this study suggest that residential traffic-related air pollution exposure is associated with reduced expiratory flows in schoolchildren.

A prospective, randomised, placebo controlled, double-blind, crossover study was performed in 31 consecutive middle-aged men with newly diagnosed OSAS and 15 healthy control subjects. Patients with OSAS were randomised to receive sham CPAP or effective CPAP for 12 weeks. Blood pressure, urinary catecholamine levels and plasma 8-isoprostane and NOx concentrations were obtained before and after both treatment modalities.

Patients with OSAS had significantly higher 8-isoprostane levels (median (IQR) 42.5 (29.2–78.2) vs 20.0 (12.5–52.5) pg/ml, p = 0.041, Mann-Whitney test) and lower NOx levels (264 (165–650) vs 590 (251–1465) µmol/l, p = 0.022) than healthy subjects. Body mass index, blood pressure and urinary catecholamines were unchanged by CPAP therapy, but 8-isoprostane concentrations decreased (38.5 (24.2–58.7) pg/ml at baseline vs 22.5 (16.2–35.3) pg/ml on CPAP, p = 0.0001) and NOx levels increased (280 (177–707) vs 1373 (981–1517) µmol/l, p = 0.0001) after CPAP.

OSAS is associated with an increase in oxidative stress and a decrease in NOx that is normalised by CPAP therapy.

The aim of this study was to investigate whether information about the initial inflammatory cytokine profile and markers increases the accuracy of prognostic scales to predict 30-day mortality. To this aim, a prospective cohort study in two tertiary care hospitals was designed. Procalcitonin (PCT), C-reactive protein (CRP) and the systemic cytokines tumour necrosis factor (TNF) and interleukins IL6, IL8 and IL10 were measured at admission. Initial severity was assessed by PSI (Pneumonia Severity Index), CURB65 (Confusion, Urea nitrogen, Respiratory rate, Blood pressure, ≥65 years of age) and CRB65 (Confusion, Respiratory rate, Blood pressure, ≥65 years of age) scales. A total of 453 hospitalised CAP patients were included.

The 36 patients who died (7.8%) had significantly increased levels of IL6, IL8, PCT and CRP. In regression logistic analyses, high levels of CRP and IL6 showed an independent predictive value for predicting 30-day mortality, after adjustment for prognostic scales. Adding CRP to PSI significantly increased the area under the receiver operating characteristic curve (AUC) from 0.80 to 0.85, that of CURB65 from 0.82 to 0.85 and that of CRB65 from 0.79 to 0.85. Adding IL6 or PCT values to CRP did not significantly increase the AUC of any scale. When using two scales (PSI and CURB65/CRB65) and CRP simultaneously the AUC was 0.88.

Adding CRP levels to PSI, CURB65 and CRB65 scales improves the 30-day mortality prediction. The highest predictive value is reached with a combination of two scales and CRP. Further validation of that improvement is needed.

A prospective observational study of patients admitted with community-acquired pneumonia in NHS Lothian, UK, was conducted. Multivariate regression analyses were used to evaluate factors that could predict the development of complicated parapneumonic effusion or empyema, including admission demographics, clinical features, laboratory tests and pneumonia-specific (Pneumonia Severity Index (PSI), CURB65 (New onset confusion, urea >7 mmol/l, Respiratory rate ≥30 breaths/min, Systolic blood pressure < 90 mm Hg and/or diastolic blood pressure ≤60 mm Hg and age ≥65 years) and CRB65 (New onset confusion, Respiratory rate ≥30 breaths/min, Systolic blood pressure <90 mm Hg and/or diastolic blood pressure ≤60 mm Hg and age ≥65 years)) and generic sepsis scoring systems (APACHE II (Acute Physiology and Chronic Health Evaluation II), SEWS (standardised early warning score) and systemic inflammatory response syndrome (SIRS)).

1269 patients were included in the study and 92 patients (7.2%) developed complicated parapneumonic effusion or empyema. The pneumonia-specific and generic sepsis scoring systems had no value in predicting complicated parapneumonic effusion or empyema.

Multivariate logistic regression identified albumin <30 g/l adjusted odds ratio (AOR) 4.55 (95% CI 2.45 to 8.45, p<0.0001), sodium <130 mmol/l AOR 2.70 (1.55 to 4.70, p = 0.0005), platelet count >400x10⁹/l AOR 4.09 (2.21 to 7.54, p<0.0001), C-reactive protein >100 mg/l AOR 15.7 (3.69 to 66.9, p<0.0001) and a history of alcohol abuse AOR 4.28 (1.87 to 9.82, p = 0.0006) or intravenous drug use AOR 2.82 (1.09 to 7.30, p = 0.03) as independently associated with development of complicated parapneumonic effusion or empyema. A history of chronic obstructive pulmonary disease was associated with decreased risk, AOR 0.18 (0.06 to 0.53, p = 0.002). A 6-point scoring system using these combined variables had good discriminatory value: area under the receiver operator characteristic curve (AUC) 0.84 (95% CI 0.81 to 0.86, p<0.0001).

This study has identified seven clinical factors predicting the development of complicated parapneumonic effusion or empyema. Independent validation is needed.

All patients admitted to our hospital from 2004 to 2007 for CAP were reviewed retrospectively. Patients who fulfilled any IDSA/ATS major criteria for severe CAP at the emergency department (ie, the need for mechanical ventilation or vasopressors) were excluded. The predictive characteristics of the IDSA/ATS minor criteria were compared with those of the Pneumonia Severity Index (PSI) and the CURB-65 score for hospital mortality and ICU admission.

1242 patients were studied (mean age 65.7 years, hospital mortality 14.7%). The areas under the receiver operating characteristic curves for the IDSA/ATS minor criteria were 0.88 (95% CI 0.86 to 0.91) and 0.85 (95% CI 0.81 to 0.88) for predicting hospital mortality and ICU admission, respectively. These were greater than the corresponding areas for the PSI and the CURB-65 score (p<0.05). The sensitivity, specificity, positive and negative predictive values of the minor criteria were 81.4%, 82.9%, 45.2% and 96.3%, respectively, for hospital mortality and 58.3%, 90.6%, 52.9% and 92.3%, respectively, for ICU admission. The minor criteria were more specific than the PSI and more sensitive than the CURB-65 score for both outcomes.

These findings support the use of the IDSA/ATS minor criteria to predict hospital mortality and guide ICU admission in inpatients with CAP who do not require emergency mechanical ventilation or vasopressors.

The study population consisted of 3115 Dutch children born in 1996/1997 who participated in the PIAMA (Prevention and Incidence of Asthma and Mite Allergy) birth cohort study. Data on breast feeding and asthma (based on wheeze, dyspnoea and prescription of inhaled steroids) were collected by yearly questionnaires. At 8 years, specific immunoglobulin E (IgE) to airborne allergens and bronchial responsiveness were measured. Data were analysed by logistic regression and generalised estimating equations (GEEs), and stratified by maternal and paternal allergic status.

35% (n = 1081) of the children were breast fed for >16 weeks. At 8 years of age, 12.6% (n = 392) had asthma. Breast feeding (>16 weeks vs no breast feeding) was significantly associated with a lower asthma prevalence from 3 to 8 years of age, in children of both non-allergic and allergic mothers. The inverse association between breast feeding and sensitisation to airborne allergens at 8 years was non-significant. Breast feeding was not associated with bronchial hyper-responsiveness. No interaction between breast feeding and gender, maternal allergy or paternal allergy was observed in any of the associations.

Breast feeding is associated with a lower asthma risk in children until 8 years of age without evidence of attenuation and regardless of the family history of allergy.

MEDLINE, EMBASE, CINAHL, CAB abstracts and AMED (up to November 2007), conference proceedings and bibliographies of papers were searched to identify studies of asthma, wheeze or airway responsiveness in relation to intakes and serum concentrations of vitamins A, C and E. Pooled odds ratios (OR) or mean differences (MD) with 95% confidence intervals (CI) were estimated using random effects models.

A total of 40 studies were included. Dietary vitamin A intake was significantly lower in people with asthma than in those without asthma (MD –182 µg/day, 95% CI –288 to –75; 3 studies) and in people with severe asthma than in those with mild asthma (MD –344 µg/day; 2 studies). Lower quantile dietary intakes (OR 1.12, 95% CI 1.04 to 1.21; 9 studies) and serum levels of vitamin C were also associated with an increased odds of asthma. Vitamin E intake was generally unrelated to asthma status but was significantly lower in severe asthma than in mild asthma (MD –1.20 µg/day, 95% CI –2.3 to –0.1; 2 studies).

Relatively low dietary intakes of vitamins A and C are associated with statistically significant increased odds of asthma and wheeze. Vitamin E intake does not appear to be related to asthma status.

To investigate the association of variants in the PHF11 gene with asthma and associated intermediate phenotypes in two independent Western Australian population-based samples.

A linkage-disequilibrium (LD)-tagging set of 20 single nucleotide polymorphisms (SNPs) was genotyped in PHF11 in two separate populations (total n = 2315), a family-based twin study consisting of 230 families (n = 992 subjects) and a population-based nested case-control study consisting of 617 asthma cases and 706 controls. Information regarding asthma, respiratory physiology, atopy and environmental exposures was collected. Transmission disequilibrium tests, variance components models and generalised linear models were used to test for association between PHF11 SNPs and selected asthma outcomes (including longitudinal change in lung function).

After correction for multiple testing, no statistically significant (p<0.05) associations were found between PHF11 and either asthma or total serum IgE levels in either population. No statistically significant associations were found with any other asthma-associated phenotypes in either population.

Previously reported associations of PHF11 with asthma outcomes were not replicated in this study. This study suggests that PHF11 is unlikely to contain polymorphic loci that have a major impact on asthma susceptibility in our populations.

83 subjects with SSc-ILD performed a maximal cardiopulmonary exercise test with an arterial line. The agreement between peripheral oxygen saturation (Spo₂) and arterial oxygen saturation (Sao₂) was examined and survival differences between subgroups of subjects stratified on Spo₂ were analysed. Cox proportional hazards analyses were used to examine the prognostic capabilities of Spo₂.

At maximal exercise the mean (SD) difference between Spo₂ and Sao₂ was 2.98 (2.98) and only 15 subjects had a difference of >4 points. The survival of subjects with SSc-ILD whose maximum exercise Spo₂ (Spo₂max) fell below 89% or whose Spo₂max fell >4 points from baseline was worse than subjects in comparator groups (log rank p = 0.01 and 0.01, respectively). The hazard of death during the median 7.1 years of follow-up was 2.4 times greater for subjects whose Spo₂max fell below 89% (hazard ratio 2.4, 95% CI 1.1 to 4.9, p = 0.02) or whose Spo₂max fell >4 points from baseline (hazard ratio 2.4, 95% CI 1.1 to 5.0, p = 0.02).

In patients with SSc-ILD, Spo₂ is an adequate reflection of Sao₂ and radial arterial lines need not be inserted during cardiopulmonary exercise tests in these patients. Given the ease of measurement and its prognostic value, Spo₂ should be considered as a meaningful clinical and research outcome in patients with SSc-ILD.