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Treatment of advanced non-small-cell lung cancer: Italian Association of Thoracic Oncology (AIOT) clinical practice guidelines.

OBJECTIVE: AIOT (Italian Association of Thoracic Oncology) produces up-to-date, clinical practice guidelines for the management of lung cancer in Italy. Guidelines were developed by answering clinical relevant questions. Here we report only major clinical issues concerning the management of advanced non-small-cell lung cancer (NSCLC).

METHODS: A PubMed search was performed to identify published data until December 2009. Abstracts presented at the main International meetings between 2004 and 2009 were also searched. The writing committee developed and graded recommendations, which were subsequently revised by experts. The search has been subsequently updated for this manuscript in December 2010.

RESULTS: In patients with epidermal growth factor receptor (EGFR) mutation positive tumour, gefitinib is recommended as first-line treatment. In presence of EGFR mutation negative or unknown status, patients with advanced squamous NSCLC, with good performance status (PS) and without major co-morbidities, chemotherapy with third-generation regimens containing cisplatin is the recommended treatment. In non-squamous NSCLC patients, also cisplatin plus pemetrexed and platinum-based chemotherapy plus bevacizumab should be considered. Carboplatin is a valid option for patients unsuitable for cisplatin. Maintenance therapy with pemetrexed or erlotinib is a reasonable choice if allowed by reimbursement procedures and discussed with patients. Elderly patients, defined as≥70 years old, should receive third-generation single-agent chemotherapy, but in elderly patients with good PS, without major co-morbidities and with adequate organ function, platinum-based doublets with attenuated doses can be a valid option. In PS 2 patients, single-agent third-generation drug is a reasonable choice. Combination chemotherapy with carboplatin or low doses of cisplatin is a suitable alternative. For second-line treatment, two cytotoxic drugs (docetaxel and pemetrexed, the latter only in non-squamous tumours), and erlotinib, an EGFR inhibitor, are available. There are no strong data to help the choice between chemotherapy and erlotinib.

CONCLUSIONS: Many developments have been made in advanced NSCLC treatment, and the appropriate use of available therapeutic approaches and the improved understanding of lung cancer molecular abnormalities continue to enhance the outcomes on the basis of well-designed clinical trials which address critical issues in this population.

Spirometry use: detection of chronic obstructive pulmonary disease in the primary care setting.

To describe a practical method for family practitioners to stage chronic obstructive pulmonary disease (COPD) by the use of office spirometry.

The use of tunneled pleural catheters in the treatment of pleural effusions.

Tunneled pleural catheters (TPCs) have become a popular therapeutic tool for chronic pleural effusions. Although the main indication for a TPC has been recurrent, symptomatic, malignant pleural effusion, there are increasing reports of TPC usage in other medical conditions. This article will address the utility of TPCs in malignant pleural effusions, other reported uses, potential complications and catheter maintenance.

RECENT FINDINGS: The efficacy of TPCs has been well established in the setting of malignant pleural effusions and this option is now included in the guidelines addressing treatment of this condition. TPCs appear to have similar cost-effectiveness compared to chemical pleurodesis and are particularly useful in patients with trapped lung syndrome or who have shorter predicted lifespans. Attempts at bridging the benefits of pleurodesis and TPCs have been described by several groups and the recent reports have considered their use in chronic benign conditions including congestive heart failure, hepatic hydrothorax and chronic pleural infections.

SUMMARY: TPCs are an effective management strategy for symptomatic, recurrent, malignant pleural effusions. Their use as a first-line treatment is feasible and TPCs are particularly preferred for patients with trapped lung or those who are not considered good candidates for chemical pleurodesis because of short life-expectancy. There currently lacks sufficient evidence to recommend the use of TPCs in nonmalignant pleural diseases.

Adiposity and pulmonary function: Relationship with body fat distribution and systemic inflammation.

Obesity is associated with changes in pulmonary function and increased systemic inflammation. We explored the relationships among adiposity, body fat distribution indices, serum inflammatory markers and pulmonary function.

Methods: This was a post-hoc cross-sectional analysis that included subjects who had previously participated in randomized studies on obesity at our centre. Non-smoking sedentary men (282 subjects, mean age 42) without respiratory diseases were studied. BMI, waist circumference (WC), visceral and subcutaneous adipose tissue (AT), lung residual volume (RV), vital capacity (VC) and expiratory reserve volume (ERV) were measured. Serum leptin, adiponectin, tumor necrosis factor alpha (TNF-α) and high-sensitive C-reactive protein (hs-CRP) levels were measured.

Results: In subjects with metabolic syndrome (n=124), percent predicted ERV and RV were significantly associated with BMI (ERV: r=-0.19, p=0.02, RV: r=-0.28, p=0.0007), WC (r=-0.20, p=0.02, r=-0.26, p=0.002), visceral (r=-0.22, p=0.007, r=-0.25, p=0.002) and subcutaneous AT (r=-0.19, p=0.02, r=-0.28, p=0.0007). Percent predicted VC correlated with visceral (r=-0.20, p=0.02) and subcutaneous AT (r=-0.18, p=0.03). Leptin was strongly correlated with BMI (MS/no-MS: r=0.52, p=0.0005/r=0.62, p < 0.0001), WC (r=0.41, p=0.008/r=0.49, p < 0.0001), visceral (r=0.27,p=0.09/0.43, p < 0.0001) and subcutaneous AT (r=0.46, p=0.003/r=0.66, p < 0.0001), while adiponectin levels were associated in subjects with no-MS with WC (r=-0.20, p=0.01), visceral (r=-0.22, p=0.008), and subcutaneous AT (r=-0.17, p=0.05). When adjusted for anthropometric measures, neither ERV, RV nor VC was significantly correlated with serum leptin, adiponectin, TNF-α, or hs-CRP levels.

Conclusion: These results suggest that the influence of obesity on lung function in healthy subjects is mostly mediated by mechanical factors. Furthermore, not only BMI but also the pattern of fat distribution should be considered when studying associations between adiposity indices and mechanical or inflammatory variables potentially associated with pulmonary function.

PMID: 21463546 [PubMed - in process]

Probiotics and lung diseases.

Increasing awareness of the role of intestinal commensal bacteria in the development and modulation of the immune system has led to great interest in the therapeutic potential of probiotics and other bacteria-based strategies for a range of immune-related disorders.

Studies in animal models have identified strong immunomodulatory effects of many nonpathogenic bacteria and provided evidence that intestinal microbes can activate a common mucosal immune response and, thus, influence sites distant to the intestine, including the respiratory tract. Respiratory effects of probiotics in animal models have included attenuating allergic airway responses and protecting against respiratory pathogens.

Dendritic cells appear central to directing the beneficial immune response to probiotic bacteria and in translating microbial signals from the innate to the adaptive immune system, whereas regulatory T cells are emerging as potentially key effectors of probiotic-mediated responses, particularly in the reduction of allergic inflammation. Despite progress in basic research, clinical trials of probiotics in allergy/asthma and respiratory infection have been highly variable at best, leading to an undermining of confidence in this potential therapeutic strategy. It is clear that there is still much to learn regarding the determinants of the diverse immune responses elicited by different bacterial strains.

A deeper knowledge of the interactions between administered probiotics and the existing microbiota, together with an understanding of how the dialogue between microbes and the innate immune system is translated into beneficial/protective responses, will be required before we can achieve clinically effective bacteria-based strategies that maintain and promote respiratory health.

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