Objective.: Biomarkers of progression of interstitial lung disease (ILD) are needed to allow early therapeutic intervention in patients with scleroderma-associated disease (SSc-ILD).Methods.: A panel of 8 serum cytokines [interleukin 6 (IL-6), IL-8, IL-10, CCL2, CXCL10, vascular endothelial growth factor, fibroblast growth factor 2, and CX3CL1] was assessed by Luminex bead technology in exploratory cohorts of 74 patients with SSc and 58 patients with idiopathic pulmonary fibrosis (IPF). Mortality and significant lung function decline [forced vital capacity (FVC) ≥ 10%; DLCO ≥ 15%] from date of serum collection were evaluated by proportional hazards analysis. Based on these findings, the prognostic value of serum IL-6, evaluated by ELISA, was assessed in a larger test cohort of 212 patients with SSc-ILD.Results.: In the exploratory cohort, only serum IL-6 was an independent predictor of DLCO decline in both IPF and SSc-ILD. The IL-6 threshold level most predictive of DLCO decline within a year was 7.67 pg/ml. In the larger test cohort, serum IL-6 > 7.67 pg/ml was predictive of decline in FVC (HR 2.58 ± 0.98, p = 0.01) and in DLCO (HR 3.2 ± 1.7, p = 0.02) within the first year, and predictive of death within the first 30 months (HR 2.69 ± 0.96, p = 0.005). When stratified according to severity (FVC < 70%), serum IL-6 > 7.67 pg/ml was predictive of functional decline or death within the first year in patients with milder disease (OR 3.1, 95% CI 1.4–7.2, p = 0.007), but not in those with severe ILD.Conclusion.: In SSc-ILD, serum IL-6 levels appear to be predictive of early disease progression in patients with mild ILD, and could be used to target treatment in this group, if confirmed by prospective studies.

In fibrotic interstitial lung diseases, exertional breathlessness is strongly linked to health-related quality of life (HRQOL). Breathlessness is often associated with oxygen desaturation, but few data about the use of ambulatory oxygen in patients with fibrotic interstitial lung disease are available. We aimed to assess the effects of ambulatory oxygen on HRQOL in patients with interstitial lung disease with isolated exertional hypoxia. AmbOx was a prospective, open-label, mixed-method, crossover randomised controlled clinical trial done at three centres for interstitial lung disease in the UK. Eligible patients were aged 18 years or older, had fibrotic interstitial lung disease, were not hypoxic at rest but had a fall in transcutaneous arterial oxygen saturation to 88% or less on a screening visit 6-min walk test (6MWT), and had self-reported stable respiratory symptoms in the previous 2 weeks. Participants were randomly assigned (1:1) to either oxygen treatment or no oxygen treatment for 2 weeks, followed by crossover for another 2 weeks. Randomisation was by a computer-generated sequence of treatments randomly permuted in blocks of constant size (fixed size of ten). The primary outcome, which was assessed by intention to treat, was the change in total score on the King's Brief Interstitial Lung Disease questionnaire (K-BILD) after 2 weeks on oxygen compared with 2 weeks of no treatment. General linear models with treatment sequence as a fixed effect were used for analysis. Patient views were explored through semi-structured topic-guided interviews in a subgroup of participants. This study was registered with ClinicalTrials.gov, number NCT02286063, and is closed to new participants with all follow-up completed. Between Sept 10, 2014, and Oct 5, 2016, 84 patients were randomly assigned, 41 randomised to ambulatory oxygen first and 43 to no oxygen. 76 participants completed the trial. Compared with no oxygen, ambulatory oxygen was associated with significant improvements in total K-BILD scores (mean 55·5 [SD 13·8] on oxygen vs 51·8 [13·6] on no oxygen, mean difference adjusted for order of treatment 3·7 [95% CI 1·8 to 5·6]; p<0·0001), and scores in breathlessness and activity (mean difference 8·6 [95% CI 4·7 to 12·5]; p<0·0001) and chest symptoms (7·6 [1·9 to 13·2]; p=0·009) subdomains. However, the effect on the psychological subdomain was not significant (2·4 [-0·6 to 5·5]; p=0·12). The most common adverse events were upper respiratory tract infections (three in the oxygen group and one in the no-treatment group). Five serious adverse events, including two deaths (one in each group) occurred, but none were considered to be related to treatment. Ambulatory oxygen seemed to be associated with improved HRQOL in patients with interstitial lung disease with isolated exertional hypoxia and could be an effective intervention in this patient group, who have few therapeutic options. However, further studies are needed to confirm this finding. UK National Institute for Health Research.

Bronchial overproduction of leukotrienes and inhibition of prostaglandin synthesis are involved in the pathogenesis of aspirin-induced asthma. We investigated whether inhaled prostaglandin E2 (PGE2) attenuates the response to bronchial challenge with lysine acetylsalicylate (LASA) and the associated increase in urinary leukotriene E4 (u-LTE4) in seven aspirin-sensitive subjects with asthma. Each subject performed two challenges with a single dose of LASA that caused a decrease in FEV1 of 20% or more in a preliminary test, immediately after inhaling 100 micrograms PGE2 in 4 ml saline or placebo, according to a randomized double-blind protocol. FEV1 was recorded at 30-min intervals for 4 h. u-LTE4 was measured by combined high-performance liquid chromatography enzyme immunoassay at 2-h intervals. After placebo, LASA caused an obstructive reaction in all patients, with a maximum decrease in FEV1 of 35 +/- 5% with respect to baseline. u-LTE4 rose from 911 +/- 261 picograms (pg)/mg creatinine at baseline to a maximum value of 2249 +/- 748 after challenge. Inhaled PGE2 provided almost complete protection in all patients. Baseline u-LTE4 was 883 +/- 243 pg/mg creatinine and did not change significantly during the test, reaching a maximum value of 864 +/- 290 (p < 0.05 versus placebo). These results confirm that PGE2 is highly effective in preventing aspirin-induced asthma and suggest that this effect is mediated by inhibition of sulfidopeptide leukotriene production.

Controls for indoor air quality (IAQ) in schools are not usually performed throughout Europe. The aim of this study was to assess the effects of IAQ on respiratory health of schoolchildren living in Norway, Sweden, Denmark, France and Italy.In the cross-sectional European Union-funded HESE (Health Effects of School Environment) Study, particulate matter with a 50% cut-off aerodynamic diameter of 10 µm (PM₁₀) and CO₂levels in a day of normal activity (full classroom) were related to wheezing, dry cough at night and rhinitis in 654 children (10 yrs) and to acoustic rhinometry in 193 children.Schoolchildren exposed to PM₁₀>50 μg·m⁻³and CO₂>1,000 ppm (standards for good IAQ) were 78% and 66%, respectively. All disorders were more prevalent in children from poorly ventilated classrooms. Schoolchildren exposed to CO₂levels >1,000 ppm showed a significantly higher risk for dry cough (OR 2.99, 95% CI 1.65–5.44) and rhinitis (OR 2.07, 95% CI 1.14–3.73). By two-level (child, classroom) hierarchical analyses, CO₂was significantly associated with dry cough (OR 1.06, 95% CI 1.00–1.13 per 100 ppm increment) and rhinitis (OR 1.06, 95% CI 1.00–1.11). Nasal patency was significantly lower in schoolchildren exposed to PM₁₀>50 μg·m⁻³than in those exposed to lower levels.A poor IAQ is frequent in European classrooms; it is related to respiratory disturbances and affects nasal patency.

OBJECTIVES: To investigate the relation between traffic indicators in the area of residence and the occurrence of chronic respiratory disorders in children. METHODS: A population based survey was conducted in 10 areas of northern and central Italy (autumn 1994 to winter 1995) in two age groups (6-7 and 13-14 years). Information on several respiratory disorders and on traffic near residences was collected with a questionnaire given to children and to their parents. The sample analysed included 39,275 subjects (response rate 94.4%). Outcomes were: (a) early (first 2 years of life) respiratory diseases, and (b) current respiratory disorders (asthma, wheeze, cough, or phlegm in the past year). Odds ratios (ORs) and 95% confidence intervals (95% CIs), adjusted for several potential confounders, were estimated from logistic regression models. Main results were stratified by level of urbanisation (metropolitan areas, other centres). RESULTS: In the metropolitan areas, high frequency of lorry traffic in the street of residence was associated with significantly increased risks for many adverse respiratory outcomes. Among early respiratory diseases, the strongest associations were found for recurrent bronchitis (OR 1.69, 95% CI 1.24 to 2.30), bronchiolitis (1.74, 1.09 to 2.77) and pneumonia (1.84, 1.27 to 2.65), although no association was detected for episodes of wheezing bronchitis. All the current respiratory disorders were positively and consistently associated with frequency of lorry traffic, particularly the most severe bronchitic and wheezing symptoms: persistent phelgm for > 2 months (1.68; 1.14 to 2.48), and severe wheeze limiting speech (1.86; 1.26 to 2.73). No or weaker associations with heavy vehicular traffic were detected in urban and rural areas and no increased risks were found in the whole sample with the reported traffic density in the zone of residence. After extensive evaluations, the potential of reporting bias seems unlikely. CONCLUSION: Exposure to exhausts from heavy vehicular traffic may have several adverse effects on respiratory health of children living in metropolitan areas, increasing the occurrence of lower respiratory tract infections early in life and of wheezing and bronchitic symptoms at school age.