A good level of asthma control improves the quality of life of asthmatic patients and may prevent future risk in term of exacerbations and decline of pulmonary function. However, in a real-life setting, several factors contribute to generally low compliance to the treatment. A rapid-onset, long-lasting medication with few adverse effects may contribute to improve adherence to therapy, along with an effective patient education and a good physician-patient communication. Many clinical studies demonstrated the comparable efficacy of the new fluticasone propionate/formoterol (FP/F) combination in a single inhaler to other combinations of inhaled corticosteroids and β2agonists and the superiority of FP/F as compared to its individual components. Also the safety profile of this combination was encouraging in all studies, even at higher doses. By effectively and safely targeting both airway inflammation and smooth muscle dysfunction, the two pathological facets of asthma, and allowing the patient to adapt dose strength, FP/F combination in a single device represents a valid option to improve asthma control in patients with different levels of asthma severity.

The duration of antibiotic treatment of exacerbations of COPD (ECOPD) is controversial. Serum procalcitonin (PCT) is a biomarker of bacterial infection used to identify the cause of ECOPD.

BACKGROUND: Airways of lung cancer patients are often colonized by fungi. Some of these colonizing fungi, under particular conditions, produce cancerogenic mycotoxins. Given the recent interest in the infective origin of lung cancer, with this preliminary study we aim to give our small contribution to this field of research by analysing the fungal microbiome of the exhaled breath condensate of lung cancer patients from Puglia, a region of Italy. METHODS: We enrolled 43 lung cancer patients and 21 healthy subjects that underwent exhaled breath condensate and bronchial brushing collection. The fungal incidence and nature of sample collected were analysed by using a selected media for Aspergillus species. RESULTS: For the first time we were able to analyse the fungal microbioma of the exhaled breath condensate. 27.9% of lung cancer patients showed a presence of Aspergillus niger, or A. ochraceus or Penicillium ssp. while none of the healthy subjects did so. CONCLUSION: The results confirmed the high percentage of fungal colonization of the airways of lung cancer patients from Puglia, suggesting the need to conduct further analyses in this field in order to evaluate the exact pathogenetic role of these fungi in lung cancer as well as to propose efficient, empirical therapy.

Some patients with COPD report frequent acute exacerbations (AECOPD) of the disease (FE), whereas others suffer them infrequently (IE). Because the current diagnosis of exacerbation relies on patient's perception of increased symptoms (mostly dyspnoea), we hypothesised that dyspnoea perception might be different in COPD patients with FE (≥2 exacerbations or 1 hospitalisation due to AECOPD in the previous year) or IE (≤1 exacerbation in the previous year), AECOPD being defined by the institution antibiotics and/or steroids treatment, or hospital admission.

The role of disability and its association with patient-reported outcomes in the nonsevere forms of chronic obstructive pulmonary disease (COPD) has never been explored.

Obstructive sleep apnea syndrome (OSAS) is a common breathing disorder; obesity represents a major risk factor for the development and progression of OSAS although obese patients do not necessarily suffer from OSAS. Adipose tissue communicates with lung in both physiologic and pathologic conditions through the production of adipokines, hormones active in metabolic and inflammatory processes. To explore the extent to which Acrp30 impacts on pathophysiology of OSAS and whether these proteins could be considered as targets for both diagnosis and therapy through enzyme-linked immunosorbent assay, western blotting analysis and fast protein liquid chromatography we have analyzed total levels as well as oligomer distribution in OSAS patients. Our data demonstrated that total Acrp30 serum levels were statistically reduced in OSAS patients compared to controls (p value = 0.02). Within a selected subgroup of OSAS patients with a BMI<30, Acrp30 levels were still statistically lower in OSAS than in control group (p value < 0.05). In addition, more severe patients (AHI>15) exhibited a more pronounced reduction of Acrp30 levels. Interestingly, this reduction is mainly due to a specific decrease of the HMW oligomers, those exhibiting major biological significance. In conclusion, our results strongly suggest a role for Acrp30 oligomerization in OSAS; in fact, the down-regulation of Acpr30 and its HMW oligomers seems to be correlated to illness status independently of concomitant presence of obesity. In addition, this reduction is mainly due to the high-weight oligomers of Acrp30 suggesting a functional role of this adipokine in OSAS.

In recent years the interest in investigation of the lungs by non-invasive means including sputum induction, exhaled nitric oxide, electronic nose and measurement of biomarkers in exhaled breath has been increasing. The collection of exhaled breath condensate (EBC) has recently received acclaim by identifying mediators that are both more and more sensitive and specific. The fact that great attention is being paid to this biological sample is evident from the increasing number of scientific papers available as well as the seminars, symposia and workshops that scientific societies have organized on this topic. However, the method for the collection and analysis of the EBC has not yet been standardized and none of the biomarkers studied has been validated sufficiently to allow a use in clinical practice. The hope is, as was the case with eNO and induced sputum, that exhaled breath condensate may also soon move away from the research laboratory to clinical and ambulatory practice and from there to home monitoring of the main respiratory diseases.

The exhaled breath temperature (EBT) has been proven to be the expression of airways inflammation as well as of the increased vascularity. Although both these conditions characterize lung cancer pathogenesis, this is the first study where the EBT has been analysed in patients affected by non-small-cell lung cancer. The aim of this study was to verify whether and how the lung cancer being examined influences the EBT for possible future clinical implications. Eighty-two consecutive subjects with a radiological suspicion of lung cancer were enrolled and underwent standard diagnostic and staging procedures for cancer. EBT was measured in all the subjects at the enrolment with the X-Halo device. Forty patients resulted as affected by lung cancer while 42 as false-positive (controls). We found a higher EBT in NSCLC patients compared to healthy subjects. The EBT was correlated with number of packs/year and associated with the stage of lung cancer. We identified a cut-off value for the EBT that is able to screen patients with lung cancer with a high sensitivity and specificity. Our results suggest that lung cancer causes an increase in the EBT, which, whether confirmed and validated, could become a new non-invasive clinical tool in the screening and monitoring of this disease.

BACKGROUND AND AIMS: Lung cancer has recently been associated with human papilloma virus (HPV) infection. The most important event associated with HPV infection in cancer foresees HPV DNA integration into the host genome. Sites of integration such as the fragile site FRA3B adjacent to the FHIT frequently undergo microsatellite alterations (MAs). In this study we aim to verify the role of MAs at 3p in non-small cell lung cancer (NSCLC) with HPV positivity and eventual correlation with sex, histotype, TNM stage and cigarette smoking. METHODS: We enrolled 26 NSCLC patients previously investigated for the presence of HPV in their airways (11 HPV+ and 15 HPV-). All subjects had allelotyping analysis of DNA from exhaled breath condensate (EBC), blood and bronchial brushing of microsatellite D3S1300 located in the chromosomal region 3p. RESULTS: For the first time we described the presence of MAs at 3p in EBC of NSCLC patients with HPV positivity. MAs in EBC corresponded to those in paired brushing. The number of patients with 3p MAs was higher in the group of NSCLC with HPV positivity than with HPV negativity. No relationship between the presence and type of MAs in EBC-brushing/DNA and sex, histotype or tumor stage was found. CONCLUSION: Our results suggested that MAs at 3p are present in caucasic NSLC HPV+ patients and might be involved in lung carcinogenesis. In consideration of the possible clinical usefulness of the analysis of MAS at 3p in the EBC of HPV+ patients in the non-invasive screening for lung cancer, these results merit further studies.

BACKGROUND AND OBJECTIVES: Airway remodeling is a main feature of asthma. Different biological phenotypes of severe asthma have been recently recognized by the ENFUMOSA study group and among these one is characterized by neutrophilic airway inflammation. Concentrations of MMP-9 in airways have been suggested as a marker to monitor airway remodeling in asthma. OBJECTIVE: The aim of the present study was to explore airway remodeling in different biological phenotypes of asthma by measuring MMP-9 in EBC and correlating these with other variables. METHODS: Sixty consecutive subjects with asthma and 20 healthy controls were enrolled in the study. Exhaled MMP-9, pH and NO levels and inflammatory cells in sputum were measured in all subjects enrolled. RESULTS: We observed an increase of exhaled MMP-9 in asthmatic subjects compared to controls. Higher exhaled MMP-9 concentrations were described in severe asthmatics compared to mild to moderate especially in those with neutrophilic airway inflammation. We further found a correlation between exhaled MMP-9 and percentage of neutrophils in sputum, FEV1, exhaled NO and pH. CONCLUSION: Our results seem to substantiate the feasibility of measuring exhaled MMP-9 in the breath of asthmatic patients. MMP-9 may be considered a proxy of the amount of the ongoing airway remodeling in asthma. MMP-9 has been shown to be differentially released in different phenotypes of asthma. The measure of exhaled MMP-9 could help to monitor the ongoing airway remodeling, recognize severe stages of asthma, and possibly help determine the appropriate choice of therapy.

International guidelines describe asthma control as the main outcome of asthma management. Prevention of symptoms, improved quality of life, and reduction of exacerbations are the main components, consequently decreasing health care costs. However, many of these objectives remain unmet in real life: several surveys show that a large proportion of asthmatic patients are not well controlled despite the efficacy of current available treatment. Several randomized controlled clinical trials indicate that combining inhaled corticosteroids and long-acting β2-agonists, by means of a single inhaler, greatly improves the management of the disease. The results of 9 multicenter phase III clinical studies demonstrate that the fixed combination of fluticasone propionate/formoterol in a single inhaler is effective in terms of lung function and symptom control. These studies highlight the dose flexibility, safety and tolerability of this new inhaled combination. These characteristics meet the recommendations of international guidelines, and the preferences of respiratory physicians who identified these aspects as critical components of a successful asthma therapy. Combination of fluticasone propionate/formoterol in a single inhaler provides potent anti-inflammatory activity of fluticasone propionate and rapid onset of action of the β2-agonist formoterol making this association a viable treatment option both in terms of effectiveness and compliance.

This article deals with the prevalence and the possible reasons of COPD underestimation in the population and gives suggestions on how to overcome the obstacles and make the correct diagnosis in order to provide the patients with the appropriate therapy. COPD is diagnosed in later or very advanced stages. In Italy the rate of COPD under-diagnosis ranges between 25 and 50% and, as a consequence, the patient does not consult his doctor until the symptoms have worsened, mainly due to exacerbations. A missed diagnosis influences the timing of therapeutic intervention, thus contributing to the evolution into more severe stages of the illness. An incisive intervention to limit under-diagnosis cannot act only in remittance (passive diagnosis), but must be the promoter for a series of preventive actions: primary, secondary and rehabilitative. To reduce under-diagnosis, some actions need to be taken, such as screening programs for smokers subjects, use of questionnaires aimed to qualify and monitor the disease severity, spirometry, early diagnosis. There is a consensus regarding diagnoses based on screening of at-risk subjects and symptoms, rather than screening of the general population. In practice, all individuals over 40 years of age with risk factors should make a spirometry test. Screening actions on a national scale can be the following: compilation of questionnaires in waiting rooms of doctor's offices or performing simple maneuvers to evaluate the expiratory force at pharmacies. It is now widely recognized that COPD is a complex syndrome with several pulmonary and extrapulmonary components; as a result, the airway obstruction as assessed by FEV1 by itself does not adequately describe the complexity of the disease and FEV1 cannot be used alone for the optimal diagnosis, assessment, and management of the disease. The identification and subsequent grouping of key elements of the COPD syndrome into clinically meaningful and useful subgroups (phenotypes) can guide therapy more effectively. In conclusion, we firmly believe that an early and correct diagnosis can influence positively the progress of the disease (lowering the lung function impairment), decrease the risk of exacerbations, relieve symptoms and increase the patients' quality of life leading also to a decrease in costs associated to the exacerbations and hospitalization of the patient.

Pulmonary arterial hypertension (PAH) is a life-threatening complication of HIV infection. The prevalence of HIV-associated PAH (HIV-PAH) seems not to be changed over time, regardless of the introduction of highly active antiretroviral therapy (HAART). In comparison with the incidence of idiopathic PAH in the general population (1-2 per million), HIV-infected patients have a 2500-fold increased risk of developing PAH. HIV-PAH treatment is similar to that for all PAH conditions and includes lifestyle changes, general treatments and specific treatments.

Recently the exhaled breath temperature (EBT) was seen to increase in non-small cell lung cancer and was subsequently proposed as a possible non-invasive tool for its diagnosis. The need for further studies that confirm the previous findings and support the potential scope of this method underlies the main aim of this study that seeks to explore the pathogenic mechanisms determining the EBT in lung cancer. We enrolled 44 consecutive patients with a radiological suspicion of lung cancer and ten healthy non-smoker volunteers, after which their EBT was measured. On the same day, the subjects underwent breath condensate collection for the measurement of leukotriene (LTB)-4 and of the vascular endothelial growth factor (VEGF), the former being a marker of airways inflammation and the latter of neoangiogenesis. We confirmed the presence of a higher EBT in lung cancer patients compared to the controls. The multiple linear regression model showed that the exhaled VEGF was the only predictor of elevations of EBT. In conclusion, it can be stated that for the first time in this study, we have shown that EBT is higher in subjects with lung cancer and that the airways angiogenesis drives the increase in EBT in lung cancer. Moreover, the study suggests the potential for the use of EBT in monitoring the lung cancer progression, although the implementation of more in-depth studies to verify this result is recommended.

Obstructive Sleep Apnea (OSAS) is a disease associated with the increase of cardiovascular risk and it is characterized by repeated episodes of Intermittent Hypoxia (IH) which inducing oxidative stress and systemic inflammation. Mitochondria are cell organelles involved in the respiratory that have their own DNA (MtDNA). The aim of this study was to investigate if the increase of oxidative stress in OSAS patients can induce also MtDNA alterations.

Sleep-disordered breathing causes a burden to the sufferer, the health care system and the society. Most studies have focused on obstructive sleep apnea (OSA); however, the prevalence of comorbidities in patients affected by overlap syndrome (OS) and obesity hypoventilation syndrome (OHS) has not been carefully evaluated.

Treatment guidelines for patients with moderate persistent asthma recommend regular therapy with a combination of an inhaled corticosteroid and a longacting β2 agonist plus as-needed rapid-acting bronchodilators. We investigated whether symptom-driven budesonide and formoterol combination therapy administered as needed would be as effective as regular treatment with this combination plus as-needed symptom-driven terbutaline for patients with moderate asthma.

Background: The aim of this study was to define the involvement of some biomarkers in patients with COPD and Pulmonary Hypertension (PH), with particular attention to subgroups with a PH that is "out of proportion". Materials and Methods: Patients with COPD without PH, with PH and marked airways obstruction and with PH and mild airways obstruction were compared. Assays for human IL-6, Leukotriene B4 (LTB4), VIP and Endotelin 1 (ET-1) were performed on the blood samples taken during RHC in a pulmonary artery. Results: 83 patients were enrolled and divided into three groups: 37 simple COPD (mPAP <25 mmHg); 46 COPD with PH (mPAP ≥25 mmHg) and, among the latter, those who had an mPAP ≥35mmHg and FEV1≥50% were classified as "out of proportion" (OP) 7 patients. Patients with PH were older and had a BMI higher than the other groups; moreover, they had lower FEV1 and DLCO. A lower level of PaO2 was observed in the group of OP patients. The levels of ET-1, IL-6 and LTB4 were similar in each group; VIP was higher in the OP patients than in simple COPD and it was related to PAP . Conclusions: In the patients with COPD and PH and in particular in the group of out-of proportion PH, VIP is significantly increased, probably in order to correct the imbalance between vasoconstrictor and vasodilatator mediators.

Mitochondrial DNA (MtDNA) has been studied as an expression of oxidative stress in asthma, COPD, lung cancer and obstructive sleep apnea, but it has been mainly investigated systemically, although the pathogenetic mechanisms begin in the airways and only later progress to systemic circulation. The aim of this study was to investigate the MtDNA alterations in the exhaled breath condensate (EBC) of patients with asthma, COPD and asthma-COPD overlap syndrome (ACOS). In order to analyze better what happens to mitochondria, both locally and systemically, we compared MtDNA/nDNA in blood and EBC of paired patients. Thirteen (13) COPD patients, 14 asthmatics, 23 ACOS (10 according to Spanish guidelines, 13 in line with GINA guidelines) and 12 healthy subjects were enrolled. Patients underwent clinical and functional diagnostic tests as foreseen by the guidelines. They underwent blood and EBC collection. Content of MtDNA and nuclear DNA (nDNA) was measured in the blood cells and EBC of patients by Real Time PCR. The ratio between MtDNA/nDNA was calculated. For the first time we were able to detect MtDNA/nDNA in the EBC. We found higher exhaled MtDNA/nDNA in COPD, asthmatic and ACOS patients respectively compared to healthy subjects (21.9  ±  4.9 versus 6.51  ±  0.21, p  <  0.05; 7.9  ±  2.5 versus 6.51  ±  0.21, p  =  0.06; 18.3  ±  3.4 versus 6.51  ±  0.21, p  <  0.05). The level of exhaled MtDNA/nDNA was positively correlated with the plasmatic one. The levels of MtDNA/nDNA in the EBC, as expression of oxidative stress, are increased in COPD, asthmatic and ACOS patients compared to healthy subjects. These are preliminary results in a small number of well characterized patients that requires confirmation on a larger population. We support new studies directed toward the analysis of exhaled MtDNA/nDNA as a new exhaled non-invasive marker in other inflammatory/oxidative airways diseases.

Tissue Doppler imaging (TDI) is used to improve risk stratification in patients with chronic heart failure (CHF). So far, few studies have used this method to investigate the characteristics of subjects with CHF and Cheyne-Stokes breathing (CSB). The aim of this study was therefore to evaluate whether TDI assessment may predict the presence of CSB in patients with CHF.

Population ageing is constantly increasing due to rising life expectancy and consequently the percentage of the elderly patients with asthma is increasing, as well. FeNO is a biomarker of lung inflammation, currently widely used in clinical practice for asthma diagnosis and monitoring. Yet, there are no data about normal values of FeNO in patients of more than 65 years of age with normal lung function.