Viruses exacerbating chronic pulmonary disease: the role of immune modulation.

Chronic pulmonary diseases are a major cause of morbidity and mortality and their impact is expected to increase in the future. Respiratory viruses are the most common cause of acute respiratory infections and it is increasingly recognized that respiratory viruses are a major cause of acute exacerbations of chronic pulmonary diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis. There is now increasing evidence that the host response to virus infection is dysregulated in these diseases and a better understanding of the mechanisms of abnormal immune responses has the potential to lead to the development of new therapies for virus-induced exacerbations. The aim of this article is to review the current knowledge regarding the role of viruses and immune modulation in chronic pulmonary diseases and discuss avenues for future research and therapeutic implications.

Palliative radiotherapy in cancers of female genital tract: Outcomes and prognostic factors.

BACKGROUND AND PURPOSE: Metastatic and incurable cancers of the gynaecological tract (FGTC) represent a major global health burden. Systemic treatment has modest efficacy and radiotherapy is often used for local symptoms. This study combines experience from two large UK centres in palliative radiotherapy for gynaecological cancers. MATERIALS AND METHODS: Pooled data from two major centres was analysed. Advanced FGTC patients who received at least one fraction of palliative radiotherapy to the pelvis between 2013 and 2018 were included. Data collected included demographic and tumour details, radiotherapy dose fractionation and details of previous and subsequent treatment. Response was defined in terms of toxicity, symptomatic response and survival. Comorbidities were recorded using a modified ACE 27 score which is adjusted for the presence of uncontrolled FGTC in all the patients. RESULTS: A total of 184 patients were included for treatment response and toxicity; survival data was available for 165 patients. Subjective response in pre-radiotherapy symptoms was documented in 80.4%. Grade 3 or worse gastrointestinal, urinary and other (vomiting, fatigue, pain) toxicity incidence was 2.2%, 3.8%, and 2.7% respectively. No statistically significant correlation between the prescribed EQD210 and symptom control or toxicity was seen. 1 year overall survival was 25.1% (median 5.9 months). Absent distant metastases, completion of the intended course of radiotherapy, response to radiotherapy, and receipt of further lines of treatment were independent prognostic factors. CONCLUSION: Palliative radiotherapy is effective for symptoms of advanced FGTC with low toxicity. The absence of a dose response argues for short low dose palliative radiotherapy schedules to be used.

Survival Outcomes After High-dose Chemotherapy and Stem Cell Transplantation in the Salvage Setting for Relapsed or Refractory Germ Cell Cancers.

BACKGROUND/AIM: High-dose chemotherapy (HDCT) and stem cell transplantation (SCT) have been established as the standard of care in patients with relapsed germ cell tumours (GCTs). We evaluated the safety, efficacy and tolerability of HDCT/ SCT in patients with relapsed GCTs. PATIENTS AND METHODS: Twenty-eight patients with relapsed GCTs, treated with HDCT, were included in this study. The conditioning regime was carboplatin, etoposide, cyclophosphamide and paclitaxel. Clinical, radiological imaging and tumour markers determined treatment outcomes. RESULTS: Median age was 35 years (range=21-57 years) with 26 males and 2 females. Median time to first relapse was 6 months. Median time to progression after 2nd line chemotherapy was 17.3 months. Fourteen patients hadMedian survival was 62 months and 16 patients (57%) are in clinical follow-up with surveillance. CONCLUSION: In relapsed GCT patients, median survival may exceed 5 years post-HDCT and SCT.

The addition of whole-body magnetic resonance imaging to body computerised tomography alters treatment decisions in patients with metastatic breast cancer.

AIM: Accurate evaluation of distribution of disease and response to systemic anti-cancer therapy (SACT) is important in the optimal management of metastatic breast cancer. Whole-body magnetic resonance imaging (WB-MRI) has increased accuracy over computerised tomography of the chest, abdomen and pelvis (CT-CAP) for detecting liver and bone disease, but its effect on patient management is largely unexplored. This study investigates the effects of using WB-MRI alongside CT-CAP on SACT decisions in standard clinical practice for patients with metastatic breast cancer. METHODS: Metastatic breast cancer patients who had undergone WB-MRI within 14 d of CT-CAP were studied. Data on distribution and extent of disease and SACT response assessment from original WB-MRI and CT-CAP reports were compared. Contemporaneous medical records provided data on therapy decisions at each time point. RESULTS: Analyses were performed on 210 pairs of WB-MRI and CT-CAP in 101 patients. In 53.3% of episodes, WB-MRI reported additional sites of disease not reported on CT-CAP. Differences in SACT assessment were found in 28.0% of episodes, most commonly due to progressive disease (PD) on WB-MRI being reported as stable disease on CT-CAP (18.9%). Discordant SACT assessments were less common in first-line SACT than in subsequent lines of SACT (15.0% versus 41.6%; p = 0.0102). In 34.7% of episodes when SACT was changed, PD had been reported on WB-MRI only. CONCLUSIONS: SACT decisions in routine practice were altered by the use of WB-MRI. Further research is required to investigate whether earlier identification of PD by WB-MRI leads to improved patient outcomes.

Lung microbiology and exacerbations in COPD.

Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory condition in adults and is characterized by progressive airflow limitation that is not fully reversible. The main etiological agents linked with COPD are cigarette smoking and biomass exposure but respiratory infection is believed to play a major role in the pathogenesis of both stable COPD and in acute exacerbations. Acute exacerbations are associated with more rapid decline in lung function and impaired quality of life and are the major causes of morbidity and mortality in COPD. Preventing exacerbations is a major therapeutic goal but currently available treatments for exacerbations are not very effective. Historically, bacteria were considered the main infective cause of exacerbations but with the development of new diagnostic techniques, respiratory viruses are also frequently detected in COPD exacerbations. This article aims to provide a state-of-the art review of current knowledge regarding the role of infection in COPD, highlight the areas of ongoing debate and controversy, and outline emerging technologies and therapies that will influence future diagnostic and therapeutic pathways in COPD.