Dionysios Spyratos

Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS): current literature review

Asthma and chronic obstructive pulmonary disease (COPD) are chronic diseases, very common in general population. These obstructive airway illnesses are manifested with chronic inflammation affecting the whole respiratory tract. Obstruction is usually intermittent and reversible in asthma, but is progressive and irreversible in COPD. Asthma and COPD may overlap and converge, especially in older people [overlap syndrome-asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS)]. Although ACOS accounts approximately 15-25% of the obstructive airway diseases, is not well recognised because of the structure of clinical trials. COPD studies exclude asthma patients and asthma studies exclude COPD patients, respectively. It is crucial to define asthma, COPD and overlap syndrome (ACOS), as notable clinical entities, which they share common pathologic and functional features, but they are characterized from differences in lung function, acute exacerbations, quality of life, hospital impact and mortality.

Treatment of non-small cell lung cancer (NSCLC)

Radical surgery is the standard of care for fit stage I non-small cell lung cancer (NSCLC) patients. Adjuvant treatment should be offered only as part of an investigation trial. Stage II and IIIA adjuvant cisplatin-based chemotherapy remains the gold standard for completely resected NSCLC tumors. Additionally radiotherapy should be offered in patients with N2 lymph nodes. In advanced stage IIIB/IV or inoperable NSCLC pts, a multidisciplinary treatment should be offered consisted of 4 cycles of cisplatin-based chemotherapy plus a 3(rd) generation cytotoxic agent or a cytostatic (anti-EGFR, anti-VEGFR) drug.

Pneumothorax and asthma.

This review is focused on the relationship between asthma, pneumothorax and pneumomediastinum while presenting a number of case reports that include these conditions. The association between pneumothorax and asthma is not widely known. While asthma includes a common disorder and is prevalent worldwide, its morbidity and mortality is high when is associated with pneumothorax. Furthermore, the delayed diagnosis of pneumothorax while focusing on asthma includes the higher risk of coincidental pneumothorax in asthmatic patients. In addition, pneumomediastinum is considered benign and self-limiting condition that responds to conservative therapy. Although it is rare, the concurrence of pneumomediastinum with pneumothorax may prove fatal during a serious asthma attack. In conclusion, the symptoms of chest pain, dyspnea or focal chest findings when presented in asthmatic patients, must always create suspicion of pneumothorax or pneumomediastinum to the physician.

Molecular Targeted Drugs and Biomarkers in NSCLC, the Evolving Role of Individualized Therapy.

Lung cancer first line treatment has been directed from the non-specific cytotoxic doublet chemotherapy to the molecular targeted. The major limitation of the targeted therapies still remains the small number of patients positive to gene mutations. Furthermore, the differentiation between second line and maintenance therapy has not been fully clarified and differs in the clinical practice between cancer centers. The authors present a segregation between maintenance treatment and second line and present a possible definition for the term “maintenance” treatment. In addition, cancer cell evolution induces mutations and therefore either targeted therapies or non-specific chemotherapy drugs in many patients become ineffective. In the present work pathways such as epidermal growth factor, anaplastic lymphoma kinase, met proto-oncogene and PI3K are extensively presented and correlated with current chemotherapy treatment. Future, perspectives for targeted treatment are presented based on the current publications and ongoing clinical trials.

Preoperative evaluation for lung cancer resection

During the last decades lung cancer is the leading cause of death worldwide for both sexes. Even though cigarette smoking has been proved to be the main causative factor, many other agents (e.g., occupational exposure to asbestos or heavy metals, indoor exposure to radon gas radiation, particulate air pollution) have been associated with its development. Recently screening programs proved to reduce mortality among heavy-smokers although establishment of such strategies in everyday clinical practice is much more difficult and unknown if it is cost effective compared to other neoplasms (e.g., breast or prostate cancer). Adding severe comorbidities (coronary heart disease, COPD) to the above reasons as cigarette smoking is a common causative factor, we could explain the low surgical resection rates (approximately 20-30%) for lung cancer patients. Three clinical guidelines reports of different associations have been published (American College of Chest Physisians, British Thoracic Society and European Respiratory Society/European Society of Thoracic Surgery) providing detailed algorithms for preoperative assessment. In the current mini review, we will comment on the preoperative evaluation of lung cancer patients.

Airway inflammation in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is an inflammatory airway disease whose incidence and mortality increases every year. It is associated with an abnormal inflammatory response of the lung to toxic particles or gases (usually cigarette smoke). A central role in the pathophysiology has been shown to play a chronic inflammation of the airways that is expressed primarily by hypersecretion of mucus, stenosis of the smaller airways and the establishment of pulmonary emphysema. There is an increasing trend for assessing the inflammatory pattern of inflammatory airway diseases through mediators measured by noninvasive techniques. Markers in biological fluids and exhaled air have been the subject of intense evaluation over the past few years, with some of them reaching their introduction into clinical practice, while others remain as research tools. Of particular interest for the scientific community is the discovery of clinically exploitable biomarkers associated with specific phenotypes of the disease. Studying the effects of therapeutic interventions in these biomarkers may lead to targeted therapy based on phenotype and this is perhaps the future of therapeutics in COPD.

Clinical experimentation with aerosol antibiotics: Current and future methods of administration

Currently almost all antibiotics are administered by the intravenous route. Since several systems and situations require more efficient methods of administration, investigation and experimentation in drug design has produced local treatment modalities. Administration of antibiotics in aerosol form is one of the treatment methods of increasing interest. As the field of drug nanotechnology grows, new molecules have been produced and combined with aerosol production systems. In the current review, we discuss the efficiency of aerosol antibiotic studies along with aerosol production systems. The different parts of the aerosol antibiotic methodology are presented. Additionally, information regarding the drug molecules used is presented and future applications of this method are discussed.

Mortality from Occupational Exposure to Relatively Pure Chrysotile: A 39-Year Study

Background: Asbestos exposure is related to serious adverse health effects. However, there is disagreement about the relationship between chrysotile exposure and mesothelioma or lung cancer. Objectives: Our aim was to investigate the mortality rate among workers exposed to relatively pure chrysotile in an asbestos cement factory. Patients and Methods: In an asbestos cement plant opened in 1968, we prospectively studied all 317 workers. A quantity of 2,000 tons of chrysotile, with minimal amphibole contamination, was used annually until 1 January 2005. Asbestos fiber concentration was measured regularly. Date and cause of death were recorded among active and retired workers. Results: Asbestos fiber concentration was always below permissible levels. Fifty-two workers died during the study. The cause was cancer in 28 subjects; lung cancer was diagnosed in 16 of them. No case of mesothelioma was reported. Death was attributed to cardiovascular diseases in 23 subjects and to liver cirrhosis in 1. Overall mortality rate was significantly lower than that of the Greek general population, standardized mortality ratio (SMR) was 0.71 (95% CI 0.53–0.93). Mortality due to cancer was increased (SMR 1.15, 95% CI 0.77–1.67), mainly due to lung cancer mortality (SMR 1.71, 95% CI 0.98–2.78), but not significantly. Conclusions: Occupational exposure to relatively pure chrysotile within permissible levels was not associated with a significant increase in lung cancer or with mesothelioma. Decreased overall mortality of workers indicates a healthy worker effect, which – together with the relatively small cohort size – could have prevented small risks to be detected.

Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies.

Strategies to enhance the already established doublet chemotherapy regimen for lung cancer have been investigated for more than 20 years. Initially, the concept was to administer chemotherapy drugs locally to the tumor site for efficient diffusion through passive transport within the tumor. Recent advances have enhanced the diffusion of pharmaceuticals through active transport by using pharmaceuticals designed to target the genome of tumors. In the present study, five patients with non-small cell lung cancer epidermal growth factor receptor (EGFR) negative stage IIIa–IV International Union Against Cancer 7 (UICC-7), and with Eastern Cooperative Oncology Group (ECOG) 2 scores were administered platinum-based doublet chemotherapy using combined intratumoral-regional and intravenous route of administration. Cisplatin analogues were injected at 0.5%–1% concentration within the tumor lesion and proven malignant lymph nodes according to pretreatment histological/cytological results and the concentration of systemic infusion was decreased to 70% of a standard protocol. This combined intravenous plus intratumoral-regional chemotherapy is used as a first line therapy on this short series of patients. To the best of our knowledge this is the first report of direct treatment of involved lymph nodes with cisplatin by endobronchial ultrasound drug delivery with a needle without any adverse effects. The initial overall survival and local response are suggestive of a better efficacy compared to established doublet cisplatin–based systemic chemotherapy in (higher) standard concentrations alone according to the UICC 7 database expected survival. An extensive search of the literature was performed to gather information of previously published literature of intratumoral chemo-drug administration and formulation for this treatment modality. Our study shows a favorable local response, more than a 50% reduction, for a massive tumor mass after administration of five sessions of intratumoral chemotherapy plus two cycles of low-dose intravenous chemotherapy according to our protocol. These encouraging results (even in very sick ECOG 2 patients with central obstructive non-small cell lung cancer having a worse prognosis and quality of life than a non-small cell lung cancer in ECOG 0 of the same tumor node metastasis [TNM]-stage without central obstruction) for a chemotherapy-only protocol that differs from conventional cisplatin-based doublet chemotherapy by the route, target site, and dose paves the way for broader applications of this technique. Finally, future perspectives of this treatment and pharmaceutical design for intratumoral administration are presented.

Experimentation with inhaled bronchodilators and corticosteroids

BACKGROUND Inhaled bronchodilators and corticosteroids have been used for decades with different production systems. MATERIALS AND METHODS The following jet-nebulizers: (a) Invacare, (b) Sunmist, (c) Maxineb and ultrasound nebulizers: (a) GIMA, (b) OMRON and (c) EASY NEB II were used as production systems. The jet-nebulizers were used with different residual cups and volume filling, while the ultrasound nebulizers with different volume fillings and face mask versus inlet. RESULTS Inhalation and ultrasound process detect significant differences between the factors and interactions considered, but each technique follows a specific pattern of magnitude effect. Thus the inhaled mechanism ranks the factor effects in decreasing order: residual cup>drug>nebulizer>loading (2, 3, 4 ml) and also drug>residual cup>nebulizer (loading 8 ml). The ultrasound mechanism orders as follows: nebulizer>drug>loading. In fact, varying micro environmental conditions created during the performance of the devices in both processes alternate the magnitude of factor significance allowing for unique capacities. CONCLUSIONS PULMICORT, MAXINEB, design cup J and loading 6 ml are the best options for the inhaled process. Optimal combinations are provided by FLIXOTIDE and cup B and also by MAXINEB and cup J. The incorporation of large residual cups suggests one out of six drugs, the SUNMIST nebulizer and design D as the best choices. Ultrasound performance informs for other optimal conditions: ZYLOREN, MAXINEB, 4 ml load and MAXINEB×loading 4 ml.