In a randomised, controlled study alternate day prednisolone with an initial high dose phase ("prednisolone only series") has been compared with cyclophosphamide plus alternate day low dose prednisolone ("cyclophosphamide-prednisolone series") in 43 patients with previously untreated fibrosing alveolitis (five patients had received prednisolone in minimal dosage). In the prednisolone only series prednisolone 60 mg daily was given for one month and then reduced by 5 mg a week to 20 mg on alternate days or the minimum dose to maintain early improvement. Patients in the cyclophosphamide-prednisolone series received 100, 110, or 120 mg cyclophosphamide daily (depending on body weight) plus 20 mg prednisolone on alternate days. Treatment was continued indefinitely, or changed to the alternative regimen if the patient deteriorated, failed to improve, or developed drug toxicity. For response to treatment (as judged by change in breathlessness score, radiographic appearance, and lung function) patients were classified as improved, stable, or deteriorating. Deaths from cryptogenic fibrosing alveolitis were also analysed.Improvement had occurred at one or more assessments in seven of the 22 patients in the prednisolone only series and in five of the 21 patients in the cyclophosphamide-prednisolone series. At three years, however, only two ofthe 22 patients in the prednisolone only series were still improved and three stable, compared with one and seven of the 21 patients in the cyclophosphamideprednisolone series (three of the seven had stopped treatment because of toxicity).Life table analysis suggested better survival in patients in the cyclophosphamide-prednisolone series but this was not significant. At three years 10 of 22 patients in the prednisolone only series had died compared with three of 21 patients in the cyclophosphamide-prednisolone series. With death or failure of first treatment regimen as outcome there was a significant advantage to the patients having cyclophosphamide-prednisolone. This advantage was explained in part by the better lung volumes in this group on admission. After allowance had been made for total lung capacity (TLC), no other factor was predictive ofoutcome. Analyses ofsubgroups according to TLC on admission showed that patients with a TLC below 60% predicted did badly and those with a TLC of 80% or more predicted did well with both regimens. Patients with an initial TLC of 60-79% predicted did better with the cyclophosphamide-prednisolone regimen. Side effects were uncommon in both series and those due to cyclophosphamide resolved when treatment was stopped. The combination of cyclophosphamide with prednisolone may be an alternative to prednisolone alone with an initial high dose phase. Many patients, however, failed to respond to either treatment.

NCT00769119.

Ribavirin is a very broad-spectrum virustatic antiviral agent, first synthesised in 1972. It is characterised by low toxicity apart from reversible anaemia, usually mild. Its multiple mechanisms of action mean that viral resistance rarely develops. It can be administered orally, intravenously, or via a nebuliser. It has shown varying degrees of clinical efficacy in a variety of human diseases including respiratory tract infections due to respiratory syncytial virus and influenza, measles, herpesvirus infections, HIV infection, Lassa fever, haemorrhagic fever with renal syndrome, and (in combination with IFN-alpha) chronic hepatitis C infection. It may well prove of value against other emerging exotic infections (e.g., West Nile virus, Nipah virus).

Endogenous IL-1beta antagonists appear reduced in COPD. Furthermore, IL-1beta correlated with clinical aspects of disease severity, suggesting that IL-1beta may play a critical role in COPD. Given the relevant concentrations and binding affinities, it is likely that TNFalpha has limited activity in stable COPD.

Background: Measurements of pulmonary biomarkers can be used to monitor airway inflammation in chronic obstructive pulmonary disease (COPD), but the variability of sampled biomarkers and their inter-relationships are poorly understood. A study was undertaken to examine the intra-and inter-patient variability in spontaneous sputum samples from patients in the stable state and to describe the relationship between biomarkers, cell counts and markers of disease. Methods: Sputum interleukin-1b, tumour necrosis factor a, interleukin 8, myeloperoxidase, leucotriene B4, growthrelated oncogene a and differential cell counts were measured in patients with moderate to severe stable COPD (n = 14) on 11 occasions over a 1-month period.Results: There was significant variability in all inflammatory indices (median intra-patient coefficient of variation (CV) 35% (IQR 22-69), median inter-patient CV 102% (IQR 61-145)). Variability could be reduced by using a rolling mean of individual patient data points. Sample size calculations were undertaken to determine the number of patients required to detect a 50% reduction in neutrophil count. Using a crossover design of a putative effective treatment, the number needed using one data point per patient was 72, reducing to 23 when a mean of three data points was used. Significant correlations were demonstrated both between the inflammatory biomarkers themselves and between inflammatory biomarkers and markers of disease. Some relationships were not apparent when results from a single sample were used. The reliability of inter-relationships improved as more data points were used for each patient. Conclusions: Clear relationships exist between inflammatory biomarkers in patients with stable COPD. Sequential sampling reduced the variability of individual mediators and the potential number of patients needed to power proof of concept interventional studies.

BackgroundWe performed an analysis of UK respiratory disease epidemiology covering 2004–2012. Findings pertaining to COPD are presented here.MethodsPrevalence and incidence rates were estimated from The Health Intelligence Network database representing ∼5 per cent of the population. Mortality figures came from official government statistics. WHO data were used for international mortality comparisons and numbers of hospital admissions/inpatient bed-days.ResultsAn estimated 1.2 million people (2% of the population) have diagnosed COPD – considerably more than the 835,000 estimated by the Department of Health in 2011 – making COPD the second most common lung disease in the UK, after asthma. Prevalence has increased by 27% in the last decade. Incidence fell 2004–2008 but has been stable since with just under 115,000 new diagnoses in 2012. Men are more likely to be diagnosed with COPD and to die from it than women. COPD is rare under 40 and becomes commoner with age, affecting 9% of those aged >70. COPD prevalence, incidence and mortality rates are highest in Scotland and the north of England. Prevalence and incidence are over twice as great in the most deprived population quintile than in the least. Nearly 30,000 people die from COPD each year, making it the second greatest cause of death from lung disease and the UK’s fifth biggest killer. Mortality increased from 2004–2012. The UK COPD mortality rate ranks third in Europe. COPD accounts for over 140,000 hospital admissions and over a million bed days each year across the UK (1.7% of all hospital admissions and bed days). 97% of these admissions are for emergency care. London has notably more hospital admissions for COPD than other regions with similar prevalence.ConclusionsGender, location, and deprivation differences in COPD epidemiology probably largely reflect differences in smoking behaviour. COPD continues to represent an enormous burden on UK health services.

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