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Screening for lung cancer: we still need to know more

The holy grail for a screening test is that it discovers more cancers in the screened arm than in the control; that those cancers are of an earlier stage and there is, as a consequence, a stage shift towards lower stage cancers compared with the control group; that the test is acceptable to, basically, healthy individuals with low risks of serious side effects resulting from tests following a positive screen; and that the cost of a life saved, or a quality-adjusted life-year (QALY) is acceptable to the economy of the day.

Published in Thorax there is an end-of-screening report on a Danish CT-based study.1 They entered 4104 men and women, (of which 45% were women, unusually high) aged between 50 and 70 years, a 20 pack-year smoking history; lung function was recorded but was not used as an inclusion criterion. The screened group underwent five annual CTs and...

MDR, XDR, TDR tuberculosis: ominous progression

Any man's death diminishes me because I am involved in mankind, and therefore never send to know for whom the bell tolls; it tolls for thee... (John Donne, Meditation XV11)

The growing TB epidemic is no longer an emergency only for those who care about health, but also for those who care about justice. (P D O Davies)

For 2 weeks in January, India coughed and the rest of the world paid attention. Drug-resistant tuberculosis (TB), languishing from a decade of neglect by the Indian Revised National Tuberculosis Control Program (RNTCP), was headline news in every Indian newspaper and several international ones as well.

What captured local and international attention was a report documenting the isolation of the first cases of totally drug resistant TB (TDR-TB) from India.1 The Indian government's response, after initial denial, swung from the ridiculous to the sublime. The WHO response was...

Outpatient management of pulmonary embolism

This multi-national, randomised trial compared outpatient versus inpatient care in patients with acute pulmonary embolism with a low risk of death (severity index category of I or II). Both groups were treated with enoxaparin (≥5 days) and oral anticoagulation (≥90 days).

One of the 171 outpatients and none of the 168 inpatients had recurrence of venous thromboembolism within 90 days, meeting the non-inferiority criteria (<4% between group difference). With respect to secondary outcomes, two outpatients and no inpatients had major bleeding (intramuscular haematomas) within 14 days. There was one death in each group, neither related to the trial. There was no statistically significant difference in use of medical resources between groups. However, the outpatients had non-significantly more home visits for enoxaparin injections.

The limitations of this trial include the fact that it was an open-label trial, although steps were taken to reduce bias. In addition, the enoxaparin regime used was 1 mg/kg twice a...

Revisiting intrapleural fibrinolysis in empyema

In this double-blind, double-dummy, factorial trial performed across 11 centres in the UK, tissue plasminogen activator (t-PA) was used in combination with DNase in the treatment of pleural infection and compared with double placebo. Each treatment individually was also compared with the placebo group.

The primary end point measured the percentage change in area of pleural opacity seen on chest x-ray between day 1 and day 7. The study also used the relative change in opacity, proportions of patients referred for surgery at 3 and 12 months, duration of hospital stay, pleural fluid volume drained, change in inflammatory markers, death and any adverse events as additional end points.

The combination of t-PA and DNase led to a significant reduction in lung opacity compared with placebos. Use of either t-PA or DNase alone had no significant effect. Of the secondary end points, a significant reduction in referral for surgery and hospital...

Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension

Background

Pulmonary arterial hypertension (PAH) is a commonly fatal pulmonary vascular disease that is often diagnosed late and is characterised by a progressive rise in pulmonary vascular resistance resulting from typical vascular remodelling. Recent data suggest that vascular damage plays an important role in the development of radiation-induced pulmonary toxicity. Therefore, the authors investigated whether irradiation of the lung also induces pulmonary hypertension.

 Methods

Different sub-volumes of the rat lung were irradiated with protons known to induce different levels of pulmonary vascular damage.

 Results

Early loss of endothelial cells and vascular oedema were observed in the irradiation field and in shielded parts of the lung, even before the onset of clinical symptoms. 8 weeks after irradiation, irradiated volume-dependent vascular remodelling was observed, correlating perfectly with pulmonary artery pressure, right ventricle hypertrophy and pulmonary dysfunction.

 Conclusions

The findings indicate that partial lung irradiation induces pulmonary vascular remodelling resulting from acute pulmonary endothelial cell loss and consequential pulmonary hypertension. Moreover, the close resemblance of the observed vascular remodelling with vascular lesions in PAH makes partial lung irradiation a promising new model for studying PAH.

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