Tumour islet Foxp3+ T-cell infiltration predicts poor outcome in nonsmall cell lung cancer.

The impact of host immunity on outcome in nonsmall cell lung cancer (NSCLC) is controversial. We examined the relationship between lymphoid infiltration patterns in NSCLC and prognosis.Tumour- and stroma-infiltrating CD3(+), CD8(+) and forkhead box P3 (Foxp3)(+) T-lymphocytes were identified using immunohistochemistry and a novel image analysis algorithm to assess total, cytotoxic and regulatory T-lymphocyte counts, respectively, in 196 NSCLC cases. The median cell count was selected as a cut-point to define patient subgroups and the ratio of the corresponding tumour islet:stroma (TI/S) counts was determined.There was a positive association between overall survival and increased CD8(+) TI/S ratio (hazard ratio (HR) for death 0.44, p<0.001) but an inverse relationship between Foxp3(+) TI/S ratio and overall survival (HR 4.86, p<0.001). Patients with high CD8(+) islet (HR 0.48, p<0.001) and Foxp3(+) stromal (HR 0.23, p<0.001) counts had better survival, whereas high CD3(+) and CD8(+) stromal counts and high Foxp3(+) islet infiltration conferred a worse survival (HR 1.55, 2.19 and 3.14, respectively). By multivariate analysis, a high CD8(+) TI/S ratio conferred an improved survival (HR 0.48, p=0.002) but a high Foxp3(+) TI/S ratio was associated with worse survival (HR 3.91, p<0.001).Microlocalisation of infiltrating T-lymphocytes is a powerful predictor of outcome in resected NSCLC.

Transseptal transcatheter coil embolization of a symptomatic pulmonary arteriovenous aneurysm in a patient with hereditary hemorrhagic telangiectasia.

An atrial transseptal approach was used for embolization of a pulmonary arteriovenous aneurysm in a 56-year-old man with hereditary hemorrhagic telangiectasia. Two previous attempts at embolization of the aneurysm failed because of an inability to cannulate the feeding vessel. A transseptal puncture was performed to gain access to the left superior pulmonary vein allowing retrograde cannulation of the venous sac and successful coiling of the aneurysm without complications. Transseptal transcatheter coiling is a feasible method of treating pulmonary arteriovenous malformations if access to the feeding artery cannot be gained by a standard approach.

The role of inflammation in the pathogenesis of non-small cell lung cancer.

The link between chronic immune activation and tumorigenesis is well established. Compelling evidence has accumulated that histologic assessment of infiltration patterns of different host immune response components in non-small cell lung cancer specimens helps identify different prognostic patient subgroups. This review provides an overview of recent insights gained in the understanding of the role played by chronic inflammation in lung carcinogenesis. The usefulness of quantification of different populations of lymphocytes, natural killer cells, macrophages, and mast cells within the tumor microenvironment in non-small cell lung cancer is also discussed. In particular, the importance of assessment of inflammatory cell microlocalization within both the tumor islet and surrounding stromal components is emphasized.

Early discharge care with ongoing follow-up support may reduce hospital readmissions in COPD.

BACKGROUND: Early discharge care and self-management education, although effective in the management of chronic obstructive pulmonary disease (COPD), do not typically reduce hospital re-admission rates for exacerbations of the disease. We hypothesized that a respiratory outreach programme that comprises early discharge care followed by continued rapid-access out-patient support would reduce the need for hospital readmission in these patients. METHODS: Two hundred and forty-six patients, acutely admitted with exacerbations of COPD, were recruited to the respiratory outreach programme that included early discharge care, follow-up education, telephone support and rapid future access to respiratory out-patient clinics. Sixty of these patients received self-management education also. Emergency department presentations and admission rates were compared at six and 12 months after, compared to prior to, participation in the programme for the same patient cohort. RESULTS: The frequency of both emergency department presentations and hospital admissions was significantly reduced after participation in the programme. CONCLUSIONS: Provision of a respiratory outreach service that includes early discharge care, followed by education, telephone support and ongoing rapid access to out-patient clinics is associated with reduced readmission rates in COPD patients.

Central pathways for cough in man--unanswered questions.

Central processing of afferent cough impulses occurs in a putative 'cough centre' in the dorsal medulla where the reflex is subject to considerable cortical control. Little is known about the central neurotransmitters and mediators which mediate cough in humans. Previous animal and human studies suggest that the antitussive effect of opiates may be mediated at central 5-HT receptors. In three studies in healthy human volunteers, we have investigated the potential role of central cholinergic and dopaminergic receptors in the mediation of cough, and the potential role of 5-HT receptors in the antitussive action of opiates. Intravenous administration of atropine or physostigmine had no effect on capsaicin-induced cough. Similarly, oral administration of L-dopa, bromocriptine or haloperidol had no effect on capsaicin-induced cough. Compared with saline, intravenous morphine significantly suppressed capsaicin-induced cough and increased drowsiness. Compared with placebo, pretreatment with oral pizotifen significantly attenuated the antitussive effect of morphine, but not the sedative effect. This suggests that in humans, an agonist action at 5-HT2 and/or 5-HT1 receptors may be involved in the antitussive effect of morphine, but not its sedative effect. Further knowledge of central cough pathways in humans must await the availability of more selective receptor agonists and antagonists for human studies. This offers the promise of effective antitussive therapy. The challenge is to find an antitussive agent which can return the abnormal sensitivity of the cough reflex to normal, without adverse effects.