Effect of time and day of admission on hospital care quality for patients with chronic obstructive pulmonary disease exacerbation in England and Wales: single cohort study.

OBJECTIVE: To evaluate if observed increased weekend mortality was associated with poorer quality of care for patients admitted to hospital with chronic obstructive pulmonary disease (COPD) exacerbation. DESIGN: Prospective case ascertainment cohort study. SETTING: 199 acute hospitals in England and Wales, UK. PARTICIPANTS: Consecutive COPD admissions, excluding subsequent readmissions, from 1 February to 30 April 2014 of whom 13 414 cases were entered into the study. MAIN OUTCOMES: Process of care mapped to the National Institute for Health and Care Excellence clinical quality standards, access to specialist respiratory teams and facilities, mortality and length of stay, related to time and day of the week of admission. RESULTS: Mortality was higher for weekend admissions (unadjusted OR 1.20, 95% CI 1.00 to 1.43), and for case-mix adjusted weekend mortality when calculated for admissions Friday morning through to Monday night (adjusted OR 1.19, 95% CI 1.00 to 1.43). Median time to death was 6 days. Some clinical processes were poorer on Mondays and during normal working hours but not weekends or out of hours. Specialist respiratory care was less available and less prompt for Friday and Saturday admissions. Admission to a specialist ward or high dependency unit was less likely on a Saturday or Sunday. CONCLUSIONS: Increased mortality observed in weekend admissions is not easily explained by deficiencies in early clinical guideline care. Further study of out-of-hospital factors, specialty care and deaths later in the admission are required if effective interventions are to be made to reduce variation by day of the week of admission.

Optimising prescription and titration of oxygen for adult inpatients using novel silicone wristbands: results of a pilot project at three centres.

Oxygen is the most commonly used drug in the acute hospital setting. Oxygen can be lifesaving but there is increasing evidence that it can cause harm if it is not given correctly. Prescription of oxygen, according to target saturations, has been advocated since 2008 but compliance remains at low levels. This paper describes a novel approach to improve oxygen prescription and titration in three acute hospital trusts using a colour-coded silicone wristband. The project ran for 3 months and covered more than 2,000 emergency admissions to hospital. Data was collected for oxygen prescription and titration rates for 270 patients during the project period. The wristbands showed an improvement in prescription and titration of oxygen in two out of three sites. The results support a wider controlled study of colour-coded wristbands to improve oxygen safety in secondary care.

Matrix metalloproteinase-12 (MMP-12) SNP affects MMP activity, lung macrophage infiltration and protects against emphysema in COPD.

BACKGROUND: Recent genetic and animal studies have implicated matrix metalloproteinase-12 (MMP-12) in the pathogenesis of chronic obstructive pulmonary disease (COPD). It has previously been shown that individuals homozygous for the A/A allele of rs652438 in MMP-12 are over-represented among patients with severe COPD (n=1517). A study was undertaken to examine the functional basis of these findings. METHODS: rs652438 A and G variants were generated by site-directed mutagenesis and transfected into COS7 cells where they were expressed. Casein zymography and a specific FRET activity assay were used to compare MMP-12 activity between alleles. Cell migration was examined using a transwell assay. Patients from two COPD cohorts were genotyped for rs652438 and associated with inflammatory cell number in bronchoalveolar lavage fluid (n=10) and induced sputum (n=262); the emphysema score (n=1428) was assessed by CT scanning. RESULTS: Mean MMP activity was 2.95-fold higher by zymography (p=0.0049) and 3.45-fold higher by FRET assay (p=0.0001) for the A allele than the G allele. Mean migration of COS7 cells expressing the A allele was 2.31-fold greater than for those expressing the G allele (p=0.0001). Macrophage numbers were greater in bronchoalveolar lavage fluid (1.28-fold increase, p=0.033) and induced sputum (1.58-fold increase, p=0.083) of A/A individuals compared with A/G heterozygotes. The presence of the A allele was dose-dependently associated with increased emphysema (p=0.016). CONCLUSIONS: The rs652438 SNP alters MMP-12 activity with the A allele being more active, which is associated with increased macrophage infiltration and emphysema in the lungs of patients with COPD. These findings further implicate MMP-12 and this SNP in COPD.

MMP-9 protein level does not reflect overall MMP activity in the airways of patients with COPD.

BACKGROUND: Animal and human studies have implicated an imbalance of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the pathogenesis of chronic obstructive pulmonary disease (COPD). MMP-9 protein is increased in COPD and we hypothesized that total MMP activity would be raised although this has not previously been measured. METHODS: Using fluorescence and biotin labelled MMP assays, RT-PCR, western blotting and enzyme-linked immunosorbent assay we examined total MMP activity, specific gelatinase, elastase, collagenase activity, TIMP-1 and TIMP-2 in induced sputum from smokers with COPD and smokers without COPD. RESULTS: Induced sputum was obtained from 15 smokers with COPD and 14 smokers without COPD. MMP-9 levels were higher in those with COPD compared with controls (p<0.05). Total MMP activity, specific gelatinase, collagenase and elastase activities were not higher in COPD patients. In addition, reduced MMP activity was correlated with increasing airflow obstruction in COPD (p=0.016). CONCLUSION: MMP-9 protein but not MMP activity was higher in sputum of COPD patients compared with controls. These results suggest that MMP-9 levels may not reflect the overall MMP activity in the airways of patients with COPD suggesting a complex relationship between MMP-9 protein and activity. Further studies of MMPs in COPD should comprise activity measures in addition to protein levels.