Donato Lacedonia

Moving from the Oslerian paradigm to the post-genomic era: are asthma and COPD outdated terms?

In the majority of cases, asthma and chronic obstructive pulmonary disease (COPD) are two clearly distinct disease entities. However, in some patients there may be significant overlap between the two conditions. This constitutes an important area of concern because these patients are generally excluded from randomised controlled trials (mostly because of smoking history in the case of asthma or because of significant bronchodilator reversibility in the case of COPD). As a result, their pathobiology, prognosis and response to therapy are largely unknown. This may lead to suboptimal management and can limit the development of more personalised therapeutic options. Emerging genetic and molecular information coupled with new bioinformatics capabilities provide novel information that can pave the way towards a new taxonomy of airway diseases. In this paper we question the current value of the terms ‘asthma’ and ‘COPD’ as still useful diagnostic labels; discuss the scientific and clinical progress made over the past few years towards unravelling the complexity of airway diseases, from the definition of clinical phenotypes and endotypes to a better understanding of cellular and molecular networks as key pathogenic elements of human diseases (so-called systems medicine); and summarise a number of ongoing studies with the potential to move the field towards a new taxonomy of airways diseases and, hopefully, a more personalised approach to medicine, in which the focus will shift from the current goal of treating diseases as best as possible to the so-called P4 medicine, a new type of medicine that is predictive, preventive, personalised and participatory.

Neutrophilic airways inflammation in lung cancer: the role of exhaled LTB-4 and IL-8

BackgroundRecent advances in lung cancer biology presuppose its inflammatory origin. In this regard, LTB-4 and IL-8 are recognized to play a crucial role in neutrophil recruitment into airways during lung cancer.Notwithstanding the intriguing hypothesis, the exact role of neutrophilic inflammation in tumour biology remains complex and not completely known.The aim of this study was to give our contribution in this field by investigating LTB-4 and IL-8 in the breath condensate of NSCLC patients and verifying their role in cancer development and progression.MethodWe enrolled 50 NSCLC patients and 35 controls. LTB-4 and IL-8 concentrations were measured in the breath condensate and the blood of all the subjects under study using EIA kits. Thirty NSCLC patients and ten controls underwent induced sputum collection and analysis.ResultsLTB-4 and IL-8 resulted higher in breath condensate and the blood of NSCLC patients compared to controls. Significantly higher concentrations were found as the cancer stages progressed. A positive correlation was observed between exhaled IL-8 and LTB-4 and the percentage of neutrophils in the induced sputum.ConclusionThe high concentrations of exhaled LTB-4 and IL-8 showed the presence of a neutrophilic inflammation in the airways of NSCLC patients and gave a further support to the inflammatory signalling in lung cancer. These exhaled proteins could represent a suitable non-invasive marker in the diagnosis and monitoring of lung cancer.

Non-invasive study of airways inflammation in sleep apnea patients

The current view foresees that airway inflammation and oxidative stress are both important in the pathophysiology of obstructive sleep apnea syndrome (OSAS). Notwithstanding the fact that these events play a key role in OSAS, their monitoring is not included in the current management of this disease. The direct sampling of airways is made possible today thanks to what can be defined as quite invasive techniques, such as bronchoscopy with broncho-lavage and biopsy. Recently there has been increasing interest in the non-invasive methods that allow the study of airways via the induced sputum (IS), the exhaled breath volatile mediators and the exhaled breath condensate (EBC). The non-invasiveness of these techniques makes them suitable for the evaluation and serial monitoring of OSAS patients. The aim of this review is to spread current knowledge on the non-invasive airway markers and on their potential clinical applications in OSAS.

Characterization of obstructive sleep apnea–hypopnea syndrome (OSA) population by means of cluster analysis

Obstructive sleep apnea–hypopnea syndrome (OSA) is being identified increasingly as an important health issue. It is typified by repeated episodes of upper airway collapse during sleep leading to occasional hypoxaemia, sleep fragmentation and poor sleep quality. OSA is also being considered as an independent risk factor for hypertension, diabetes and cardiovascular diseases, leading to increased multi‐morbidity and mortality. Cluster analysis, a powerful statistical set of techniques, may help in investigating and classifying homogeneous groups of patients with similar OSA characteristics. This study aims to investigate the (possible) different groups of patients in an OSA population, and to analyse the relationships among the main clinical variables in each group to better understand the impact of OSA on patients. Starting from a well‐characterized OSA population of 198 subjects afferent to our sleep centre, we identified three different communities of OSA patients. The first has a very severe disease [apnea–hypopnea index (AHI) = 65.91 ± 22.47] and sleep disorder has a strong impact on daily life: a low level of diurnal partial pressure of oxygen (PaO2) (77.39 ± 11.64 mmHg) and a high prevalence of hypertension (64%); the second, with less severe disease (AHI = 28.88 ± 17.13), in which sleep disorders seem to be less important for diurnal PaO2 and have a minimum impact on comorbidity; and the last with very severe OSA (AHI = 57.26 ± 15.09) but with a low risk of nocturnal hypoxaemia (T90 = 11.58 ± 8.54) and less sleepy (Epworth Sleepiness Scale 10.00 ± 4.77).

HIV-associated pulmonary arterial hypertension: from bedside to the future.

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.

Quality standards for the management of bronchiectasis in Italy: A national audit

Although historically considered a neglected disease, bronchiectasis has become a disease of renewed interest over recent decades in light of an increase in prevalence and a substantial burden on healthcare systems [1–3]. In 2010, the British Thoracic Society (BTS) published guidelines on the management of bronchiectasis in adults, along with specific quality standards [4, 5]. To date, these represent the only quality standards available in Europe. These have been tested over a number of years in the UK with progressive improvements in the standard of care [6]. No national guidelines are available in Italy and no indications on which guideline should be followed have been given by the Italian Society of Respiratory Medicine (SIP). There are limited published data on the quality of bronchiectasis care in Europe outside of the UK. The BTS standards have not been tested in continental Europe or in Italy, where information on characteristics and management of bronchiectasis patients are lacking. The majority of the quality standards for the management of bronchiectasis in adults are not met in Italy http://ow.ly/YKMpU

Exhaled matrix metalloproteinase-9 (MMP-9) in different biological phenotypes of asthma ☆

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.

Dyspnea perception in asthma: Role of airways inflammation, age and emotional status

OBJECTIVES Dyspnea perception in asthmatics differs between subjects. Poor perception is usually associated with increased risk of asthma attack/exacerbation. The advanced stage of the disease and the presence of eosinophilic airways inflammation have been recently recognized as being responsible for poor dyspnea perception. However, few studies are available on this topic. DESIGN The aim of this study was to analyse the influence of inflammatory pattern, age and affective status on dyspnea perception in asthmatic subjects. SUBJECTS AND INTERVENTIONS Seventy-one consecutive asthmatic patients were recruited and underwent induced sputum, exhaled NO measurement and breath condensate collection. Perception of dyspnea was evaluated as a BORG-VAS/FEV(1) slope before and after the broncho-reversibility test and correlated with the stage of asthma, inflammatory markers, age and depression scale. RESULTS Dyspnea perception decreases with the worsening of asthma, with the advance of age and of depression status. Furthermore, airways inflammation plays a key role in the decline of dyspnea perception as proved by the negative correlation observed between inflammatory cells in sputum, exhaled pH and NO and BORG-VAS/FEV(1) slope. CONCLUSIONS The results of our study suggested that airways inflammation, depression status, advance age and severity of asthma influence dyspnea perception and suggest a straight control to identify and better manage poor preceptor asthmatics.

Could exhaled ferritin and SOD be used as markers for lung cancer and prognosis prediction purposes

Eur J Clin Invest 2012; 42 (5): 478–486

Severe obstructive sleep apnoea exacerbates the microvascular impairment in very mild hypertensives.

Background  Different studies have shown that obstructive sleep apnoea syndrome (OSAS), frequently associated with hypertension, represents a harmful and independent risk for cardiovascular diseases. The aim of our study was to ascertain whether the occurrence of OSAS could worsen microcirculatory impairment in very mild hypertensives.