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Background and aim: In patients with cystic fibrosis (CF) non-invasive ventilation (NIV) improves lung mechanics and gas exchange, and decreases the work of breathing. Domiciliary NIV is mainly used in hypercapnic patients with severe disease, because it counteracts the progression of lung functional impairment and it is often used as a useful “bridge” to lung transplantation. However, to date, there are no standardized criteria to indicate the effect of a precocious starting of NIV in patients with functional ventilation inhomogeneity without hypercapnia. In this pilot study we assessed whether an early NIV treatment might influence functional and clinical outcomes in CF patients. Methods: Six normocapnic CF patients were treated for one year with NIV. At baseline and after 1 year of NIV treatment, arterial gas analysis, spirometry, MBW to derive LCI, nocturnal cardio-respiratory polygraphy (PG), and Pittsburgh Sleep Quality Index (PSQI) were perfomed in all enrolled patients. Results: After one year, despite spirometric and LCI values remain statistically not modified, the number of infectious exacerbations was reduced by 50%. Conclusions: These results suggest that nocturnal NIV improves clinical conditions of stable CF patients. Finally, we suggest that this procedure can be useful to counteract the progression of lung disease even in normocapnic patients (www.actabiomedica.it)

The aim of this randomized open study was to evaluate the safety and efficacy of different dosages (2000 UI vs 4000 UI) of sublingual immunotherapy (SLIT) in patients with allergic diseases such as asthma associated to rhinitis and rhinoconjunctivitis sensitized to house dust mites. We enrolled 61 patients with a history of allergic asthma, and a positive skin prick test for Dermatophagoides (D.) pteronyssinus/farinae. Patients were randomly assigned to receiving SLIT at dosage of 2000 UI (Group A) or 4000 UI (Group B) maintenance dose. We evaluated: subjective symptoms using a Visual Analogic Scale (VAS), the amount of prescribed symptomatic drugs, bronchial reactivity to methacoline and side effects using a specific questionnaire. A significant improvement in symptoms, assessed by VAS, was observed with both SLIT doses with no significant differences between groups. The provocation dose of methacoline inducing a 20% fall of FEV1 significantly increased after 12 months only in the 4000 UI dose group. In conclusion, both monomeric allergoid dosages of SLIT (2000 UI and 4000 UI) are a safe and efficacy option to reduce symptoms in patients with allergic asthma caused by house dust mites. Moreover, both dosages are efficacious even to protect against airway reactivity but it seems that monomeric allergoid of SLIT at higher dosage (4000 UI) is better than at the lower dosage (2000 UI).

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Theoretically, an appropriate management of the disease should be aimed to prevent and reduce symptoms, to reduce the number and the severity of exacerbations, to improve exercise tolerance and lung function and to decrease the rate of mortality. However, the rapid progress in understanding the pathophysiologic aspects of COPD has been followed by very few advances in its management and currently there is no pharmacological treatment which is able to reduce the decline in lung function that occurs in these patients or to affect mortality. Effective symptomatic relief and improvement in exercise capacity can be obtained with inhaled bronchodilators and a new long-acting (24 h) inhaled anticholinergic, tiotropium bromide, is now available. New pharmacological approaches for COPD include the development of drugs which should be able to control the neutrophilic, steroid-insensitive inflammation, to reassess the protease/antiprotease balance and to reduce oxidative stress in the airways. While most of these drugs are still in preclinical evaluation, some recent phase II-III clinical trials have shown the beneficial effects of a new class of anti-inflammatory compounds, the phosphodiesterase-4 (PDE-4) inhibitors, in patients with COPD. Given the relevance of mucus hypersecretion in the pathophysiology of this disease, efforts have been made also to draw definitive conclusions on the effectiveness of the available mucoactive drugs and in the development of new mucoactive molecules. Further studies are required to understand the impact of each potential therapeutic strategy in the effective control of COPD.

In some asthmatics deep inspiration causes a sustained bronchoconstration, which is dependent on Ca2+ uptake. Inhaled diuretics protect against bronchoconstriction induced by a variety of indirect stimuli, by inhibiting the ionic fluxes involving Ca2+ uptake across the cell membrane of airway epithelium. The aim of this study was therefore to investigate the protective effect of inhaled furosemide on the bronchoconstriction induced by deep inspiration in asthma and to compare it with the effect of acetazolamide, an inhibitor of carbonic anhydrase devoid of effect on ion cotransport but possessing inhibitory effects on chloride ion influx and Na+/K+ exchange. The study was carried out on three different study days according to a randomized, double-blind, placebo-controlled, crossover design. Nine non smoking asthmatic subjects first performed a series of 9 controlled deep inspirations to TLC followed by forced expirations to RV within 20 min, which caused a decrease of FEV120% from baseline. Two hours later, the subjects inhaled either furosemide (40 mg), or acetazolamide (500 mg), or saline (placebo) in random order, and then two more deep-inspiration challenges were performed after 30 and 140 mins. The progressive percent decrement of FEV1 caused by deep-inspiration challenge was taken as an index of bronchoconstriction. Bronchoconstriction was significantly blunted at 30 mins, but not 140 mins, after inhaling furosemide (p0.01) or acetazolamide (p0.05) compared to control. We interpret these results as due to a modulation of ionic fluxes across the smooth muscle cell membrane afforded by inhaled furosemide and acetazolamide.

Chemoreceptors are known to respond to changes in composition of the gases in the inspired air by changing pulmonary ventilation. Whereas, less known it is the role that they play in many both physiologic and pathologic conditions. In this review we do not only consider the anatomic and physiologic chemoreceptor features but also we analyse the relationship between chemoreflex and baroreflex in the cardiovascular control, their role in the pathogenesis of essential hypertension and in the increase of blood pressure in subjects affected by obstructive sleep apnea, their implication in the genesis of dyspnea in chronic heart failure and their role in pulmonary disease. In this review we also analyse the chemoreflex changes with relation to physiologic situations such as aging, obesity, exercise, training and high altitude. Three methods are described for the study of the chemoreflex function, but more attention is paid to the new rebreathing technic. The aim of this paper is to underline the interactions between chemoreceptors and cardiovascular system and to analyse their functional changes in both physiologic and pathologic conditions.