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Objective. To investigate the correlation between respiratory failure and the pulmonary circulation. We focused on anatomical and functional changes of the right heart.Design. Clinical investigation.Methods. We evaluated 75 patients hospitalized in our respiratory ward for COPD exacerbation. All patients underwent transthoracic echocardiography and measurements of right heart chambers. Moreover all patients underwent blood tests, measurement of blood pressure, evaluation of body mass index (BMI), ECGs, pulmonary function tests, and the Saint George’s Respiratory Questionnaire (SGRQ).Results. Among 75 patients consecutively hospitalized, 56 patients with a COPD exacerbation were included in our study. We have emphasized the higher value of PAPs and the increased size of right atrial area in severe COPD patients. Significant correlation was observed between low values of PaO2and larger area of the right atrium. The measurement of TAPSE showed a right ventricular dysfunction in all patients but especially in severe COPD patients. We have obtained a significant correlation between TAPSE and arterial blood gas.Conclusions. In patients with chronic respiratory failure, blood gas parameters should be considered as negative prognostic factors of right heart failure. Respiratory failure shows a relationship with pulmonary hypertension and with the anatomy and function of the right heart sections.

Autophagy is the main cellular pathway for degradation of long-lived proteins and organelles and regulates cell fate in response to stress. Beclin 1 is a key regulator of this process. In some settings autophagy and apoptosis seem to be interconnected. Recent reports indicate that fibroblasts in idiopathic pulmonary fibrosis (IPF) acquire resistance to apoptosis. Here, we examined the expression of beclin 1, and of the anti apoptotic protein Bcl-2 in human IPF fibroblasts using immunohistochemistry and molecular biology in bioptic sections, in primary cultures of fibroblasts taken from patients with IPF and in fibroblast cell lines. Expression of beclin 1 in fibroblasts from IPF was down-regulated in comparison with fibroblasts from normal lungs while the anti-apoptotic protein Bcl-2 expression was over-expressed. Treatment of fibroblast cell cultures with cisplatin induced a significant increase in beclin 1 and caspase 3 protein levels but a reduction in Bcl-2 expression. These observations were confirmed by the analysis of acid compartments and transmission electron microscopy. Our results demonstrate a modified expression of the apoptotic beclin 1 Bcl-2 proteins in human IPF fibroblasts suggesting the existence of an autophagy/apoptosis system dysfunction.

We evaluated comorbidity, hospitalization, and mortality in chronic obstructive pulmonary disease (COPD), with special attention to risk factors for frequent hospitalizations (more than three during the follow-up period), and prognostic factors for death. Two hundred eighty-eight consecutive COPD patients admitted to respiratory medicine wards in four hospitals for acute exacerbation were enrolled from 1999 to 2000 in a prospective longitudinal study, and followed up until December 2007. The Charlson index without age was used to quantify comorbidity. Clinical and biochemical parameters and pulmonary function data were evaluated as potential predictive factors of mortality and hospitalization. FEV(1), RV, PaO(2), and PaCO(2) were used to develop an index of respiratory functional impairment (REFI index). Hypertension was the most common comorbidity (64.2%), followed by chronic renal failure (26.3%), diabetes mellitus (25.3%), and cardiac diseases (22.1%). Main causes of hospitalization were exacerbation of COPD (41.2%) and cardiovascular disease (34.4%). Most of the 56 deaths (19.4%) were due to cardiovascular disease (67.8%). Mortality risk depended on age, current smoking, FEV(1), PaO(2), the REFI index, the presence of cor pulmonale, ischemic heart disease, and lung cancer. Number and length of hospital admissions depended on the degree of dyspnea and REFI index. The correct management of respiratory disease and the implementation of aggressive strategies to prevent or treat comorbidities are necessary for better care of COPD patients.

AIM: To determine which timing of therapy with formoterol (FOR) and/or tiotropium (TIO) shows the greater and more continuous functional improvement during 24 h in patients with moderate to severe COPD. METHODS: In this randomised, blind, crossover study 80 patients with stable COPD (40 moderate and 40 severe) received 5 different bronchodilator 30-day treatments in a random order. Treatments (Tr) were: Tr1: TIO 18 microg once-daily (8 am); Tr2: TIO 18 microg (8 am) + FOR 12 microg (8 pm); Tr3: FOR 12 microg twice-daily (8 am and 8 pm); Tr4: TIO 18 microg (8 am) + FOR 12 microg twice-daily (8 am and 8 pm); Tr5: FOR 12 microg twice-daily (8 am and 8 pm) + TIO 18 microg (8 pm). Spirometries were performed during 24 h (13 steps) on Day1 and Day30. End-points were: gain of FEV(1) (DeltaFEV(1)) from baseline of the Day1 and Day30, AUC (Area Under Curve), Dyspnoea Index, and as-needed use of salbutamol. RESULTS: Sixty-eight patients completed all treatments. The greater and continuous daily functional improvement was showed during Tr4 and Tr5 (Day1 +135.8 mL and +119.1 mL; Day30 +160.2 mL, and +160.5 mL, respectively). Daily means of DeltaFEV(1) were significantly different between single-drug treatments and combination therapy. Dyspnoea was greater in single-drug treatments. Less use of rescue salbutamol was reported in Tr4 (0.80 puffs/die) and Tr5 (0.71 puffs/die). CONCLUSIONS: In patients with moderate to severe COPD, combination therapy with tiotropium administered in the morning (Tr4) was the most effective; in patients with prevailing night-symptoms, treatment with tiotropium in the evening (Tr5) reduced symptoms and use of salbutamol. Tr5 showed less variability of FEV(1) during the 24 h (CV=0.256). These results are relevant for opening new ways in clinical practice.

Background: The scientific literature does not supply enough information about the effects of postural changes on diffusing lung capacity for carbon monoxide (DLCO) in patients with chronic obstructive pulmonary disease (COPD), in particular regarding the prone position. Objectives: We evaluated posture-related changes in DLCO in healthy subjects and in COPD patients in order to especially assess how prone posture affects gas exchange. Methods: In this cross-sectional study, DLCO was measured in 10 healthy subjects and 30 COPD patients in standing, seated, supine and prone positions. Results: In healthy individuals, DLCO tended to improve from the upright to the supine position (21.42 ± 2.90 and 26.07 ± 5.11 ml/min/mm Hg, respectively); in the same group, changing the position from upright to prone also caused significant improvements in DLCO (absolute value, 21.42 ± 2.90 vs. 24.80 ± 4.39 ml/min/mm Hg, p < 0.05, or percent of predicted, 78.58 ± 11.12 vs. 91.44 ± 13.23, p < 0.05) and in DLCO proportional to alveolar volume (DLCO/VA; 4.52 ± 0.57 vs. 5.66 ± 1.48 ml/min/mm Hg/l, p < 0.05). No significant differences in DLCO have been observed in COPD patients from the standing to the prone position. Multivariate linear regression models showed that the posture-related changes in DLCO, DLCO expressed as percent of predicted and in DLCO/VA are directly correlated with the transition from upright/sitting to supine/prone. Conclusions: In healthy subjects, the effect of postural changes on DLCO could be explained by a more homogeneous perfusion, whereas the lack of variations in COPD patients could be attributed to the increased rigidity of lung capillaries, which could represent an early sensitive marker of damage of the alveolar capillary interface in these patients.

Background Our aim was to compare three‐dimensional (3D) and 2D and 3D speckle‐tracking (2D‐ STE , 3D‐ STE ) echocardiographic parameters with conventional right ventricular ( RV ) indexes in patients with chronic pulmonary hypertension ( PH ), and investigate whether these techniques could result in better correlation with hemodynamic variables indicative of heart failure. Methods and Results Seventy‐three adult patients (mean age, 53±13 years; 44% male) with chronic PH of different etiologies were studied by echocardiography and cardiac catheterization (25 precapillary PH from pulmonary arterial hypertension, 23 obstructive pulmonary heart disease, and 23 postcapillary PH from mitral regurgitation). Thirty healthy subjects (mean age, 54±15 years; 43% male) served as controls. Standard 2D measurements ( RV –fractional area change–tricuspid annular plane systolic excursion) and mitral and tricuspid tissue Doppler annular velocities were obtained. RV 3D volumes and global and regional ejection fraction (3D‐ RVEF ) were determined. RV strains were calculated by 2D‐ STE and 3D‐ STE . RV 3D global‐free‐wall longitudinal strain (3D GFW ‐ RVLS ), 2D global‐free‐wall longitudinal strain ( GFW ‐ RVLS ), apical‐free‐wall longitudinal strain, basal‐free‐wall longitudinal strain, and 3D‐ RVEF were lower in patients with precapillary PH ( P PH ( P GFW ‐ RVLS (hazard ratio 4.6, 95% CI 2.79 to 8.38, P =0.004) and 3D‐ RVEF (hazard ratio 5.3, 95% CI 2.85 to 9.89, P =0.002) were independent predictors of mortality. Receiver operating characteristic curves showed that the thresholds offering an adequate compromise between sensitivity and specificity for detecting hemodynamic signs of RV failure were 39% for 3D‐ RVEF ( AUC 0.89), −17% for 3D GFW ‐ RVLS ( AUC 0.88), −18% for GFW ‐ RVLS ( AUC 0.88), −16% for apical‐free‐wall longitudinal strain ( AUC 0.85), 16 mm for tricuspid annular plane systolic excursion ( AUC 0.67), and 38% for RV ‐ FAC ( AUC 0.62). Conclusions In chronic PH , 3D, 2D‐ STE and 3D‐ STE parameters indicate global and regional RV dysfunction that is associated with RV failure hemodynamics better than conventional echo indices.

Background It is known that obstructive sleep apnea syndrome (OSAS) can affect right ventricular (RV) performance even in the absence of systemic hypertension and other known cardiac or obstructive pulmonary disease. The purpose of the present study was to assess RV function in OSAS using 3-D echocardiography and speckle tracking echocardiography (STE) and evaluate changes after continuous positive airway pressure (CPAP) treatment. Methods Thirty-seven patients with OSAS without comorbidities and thirty control subjects were studied using 3-D echocardiography and STE. Fifteen patients underwent CPAP therapy and were studied before and after treatment. RV 3-D ejection fraction was calculated. Peak systolic strain was determined. RV dyssynchrony was defined as SD of the 6 time to peak systolic strain values. Results 3-D RV ejection fraction was lower and RV dyssynchrony was greater in patients with moderate-severe OSAS compared with control subjects in the presence and absence of pulmonary hypertension. 3-D RV ejection fraction and RV dyssynchrony were independently associated with apnea-hypopnea index. Patients treated with CPAP had significant changes in RV parameters. Conclusions 3-D RV ejection fraction and RV dyssynchrony were abnormal in OSAS patients compared with control subjects and associated with OSAS severity. RV 3-D STE abnormalities improved after chronic application of CPAP.

Neurotrophin (NT) and NT receptor expression was assessed in 12 typical (TC) and 8 atypical (AC) human pulmonary carcinoids by Western blot and immunohistochemistry. TC and AC carcinoid express to different extent NT and NT receptor proteins. Nerve growth factor (NGF) was expressed by 83% of the TC but not by the AC carcinoids. Brain derived neurotrophic factor (BDNF) was expressed by 33 and 100% of TC and AC carcinoids, respectively. NT-3 was expressed by 58% of the TC and 38% of AC carcinoids. TC carcinoids express high affinity NT receptors while 50% of the AC carcinoids express the TrkB receptor. Our results demonstrate that NGF/TrkA and BDNF/TrkB signaling need to be considered as regulatory pathways that may address survival, differentiation and/or aggressiveness of human pulmonary carcinoids. Contrarily to the BDNF/TrkB, expression of the NGF/TrkA signaling may overcome aggressiveness of carcinoid cells. NTs may be useful as markers in the clinic.

Aim of our study was to evaluate if the type of nebulizer can influence the effects of steroid aerosol therapy. We considered 27 asthmatics allergic to grasses with FEV1

Worsening of underlying bronchospasm may be associated with acute exacerbations of chronic obstructive pulmonary disease (COPD). As airway obstruction becomes more severe, the therapeutic option is to add salbutamol, but not salmeterol, as needed to cause rapid relief of bronchospasm. Unfortunately the most effective dosage of beta2-agonists may increase above that recommended during acute exacerbations. In this study, we compared the acute effects of higher than customary doses of salmeterol and salbutamol in 20 patients with acute exacerbation of COPD. A dose-response curve to salmeterol pMDI, 25 microg/puff or salbutamol pMDI, 100 microg/puff, was constructed using 1, 1, and 2 puff' i.e., a total cumulative dose of 100 microg salmeterol or 400 microg salbutamol on 2 consecutive days. After baseline measurements, dose increments were given at 30-min intervals with measurements being made 25 min after each dose. Hear rate (HR) and pulse-oximetry (SpO2) measurements were then taken. Both salmeterol and salbutamol induced a larg and significant (P0.05) dose-dependent increase in FEV1 [mean differences from baseline (L) = after 100 microg salmeterol 0.174 (95% CI: 0.112 to 0.237); after 400 microg salbutamol: 0.165 (95% CI: 0.080 to 0.249)], in IC [mean differences from baseline (L) = after 100 microg salmeterol: 0.332 (95% CI: 0.165 to 0.499); after 400 microg salbutamol: 0.281 (95% CI: 0.107 to 0.456)] (Fig. 2), and in FVC mean differences from baseline (L) = after 100 microg salmeterol: 0.224 (95% CI: 0.117 to 0.331); after 400 microg salbutamol: 0.242 (95% CI: 0.090 to 0.395)]. There was no significant difference between the FEV1 values (P=0.418), the ICvalues (P=0.585), and the FVCvalue (P=0.610) after 100 microg salmeterol and 400 microg salbutamol. HR [mean differences from baseline (beats/min) = after 100 microg salmeterol: 3.15 (95% CI: -0.65 to 6.96); after 400 microg salbutamol: 2.30 (95% CI: -0.91 to 5.51)] and SpO2 [mean differences from baseline (%) = after 100 microg salmeterol: -0.20 (95% CI: -1.00 to 0.60); after 400 microg salbutamol: -0.11 (95% CI: -1.00 to 0.79)] did not change significantly from baseline (P0.05). These data indicate that salmeterol is effective and safe in the treatment of acute exacerbation of COPD and support its use in this clinical condition.

Objective: To evaluate the acute bronchodilating effect of cumulative doses of formoterol administered via Turbuhaler™ or salmeterol administered via pressurised metered-dose inhaler (pMDI) in patients with mild acute exacerbations of chronic obstructive pulmonary disease (COPD) to determine if these drugs might be used in this condition.

Introduction. This paper presents the final results of a cross-sectional study started in 2010. It compares the perceived efficacy of different types of tobacco health warning (texts versus shocking pictures) to quit or reduce tobacco use.Methods. The study conducted between 2010 and 2012 in Italy enrolled adults smokers. Administering a questionnaire demographic data, smokers behaviors were collected. Showing text and graphic warnings (the corpse of a smoker, diseased lungs, etc.) the most perceived efficacy to reduce tobacco consumption or to encourage was quit.Results. 666 subjects were interviewed; 6% of responders referred that they stopped smoking at least one month due to the textual warnings. The 81% of the smokers perceived that the warnings with shocking pictures are more effective in reducing/quitting tobacco consumption than text-only warnings. The younger group (P<0.05.Conclusions. This study suggests that pictorial warnings on cigarette packages are more likely to be noticed and rated as effective by Italian smokers. Female and younger smokers appear to be more involved by shock images. The jarring warnings also appear to be supporting those who want to quit smoking. This type of supportive information in Italy may become increasingly important for helping smokers to change their behavior.

Acute pulmonary embolism (PE) is a common complication in hospitalized patients, spanning multiple patient populations and crossing various therapeutic disciplines. Current treatment paradigm in patients with massive PE mandates prompt risk stratification with aggressive therapeutic strategies. With the advent of endovascular technologies, various catheter-based thrombectomy and thrombolytic devices are available to treat patients with massive or submassive PE. In this paper, a variety of newer treatment strategies for PE are analyzed, with special emphasis on various interventional treatment strategies. Clinical evidence for utilizing endovascular treatment modalities, based on our institutional experience as well as a literature review, is provided.

Chronic obstructive pulmonary (COPD) is one of the major causes of morbidity and mortality in the world. COPD is characterized by chronic inflammation in the pulmonary compartment and in the systemic circulation. This disorder is associated with clinically significant alterations in biochemistry and organ function; thyroid dysfunctions are common in chronic diseases, such as COPD. Several characteristics of COPD patients could increase their likelihood of developing hypothyroidism or hyperthyroidism. The purpose of our study was to assess the impact of thyroid dysfunction in patients with COPD.We evaluated the pulmonary function tests, arterial blood gases, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and thyroid functions in patients with COPD, recruited between admissions in Respiratory Diseases Unit, Policlinico Umberto I, Rome, Italy, from June 2012 to May 2013. We selected patients with subclinical hypothyroidism (ScH), overt hypothyroidism, and hyperthyroidism, and a control group without thyroid disturbance.Our results indicate that patients with overt hypothyroidism have lower levels of pO2, MIP, and MEP compared with subjects with ScH, hyperthyroidism, and the control group. We also found a substantial tendency towards pCO2 levels increase in patients with hypothyroidism (p = 0.06).Patients with thyroid dysfunctions have a greater impairment of MIP and MEP and a negative correlation was observed between hypoxemia and TSH. Further studies are needed to investigate whether the treatment of thyroid disfunction could have a beneficial effect on COPD patients' lung function and prognosis.

The European Commission has proposed a review of the directive on tobacco products on labeling and packaging of tobacco products by introducing warning text with pictorial warning that occupies 75% of the cigarette packages. The aim of the survey was to assess the impact of plain packaging and pictorial warning in smoking reduction, cessation and initiation among a sample of adult. The cross-sectional study was conducted in Rome between September and November 2012. The questionnaires administered were 227, with a response rate of 82.4%. 35.8% (No. 67) of the respondents considered the image of the gangrene the most effective in communicating smoking-related damages, followed by the image on lung cancer (No. 60; 32.1%). Distinguishing between smokers and non-smokers (both former and never smokers), the picture on lung cancer was the most effective for smokers (No. 22; 38.6%); if cigarette packages have pictorial warnings like the ones shown, more than half (No. 33; 57.9%) of smokers would change brand; 66.7% (No. 38) of them would feel uncomfortable in showing the package. Comparing the 3 packagings, classic packaging, plain packaging with textual warning, and plain packaging with both textual and pictorial warning, the majority of people declared that the third is the most effective in preventing smoking initiation (No. 169; 90.9%), in motivating to quit (No. 158; 84.9%), and in changing smoking habits (No. 149; 80.5%). The survey, although its small sample size and being not representative of all strata of Italian population, shows that the plain packaging with pictorial warning is the most convincing in the three outcomes considered.

To date, no sufficiently sensitive and specific single marker has been found to predict the clinical course of sarcoidosis. We designed a cohort study to investigate whether a panel of biomarkers measured in bronchoalveolar lavage (BAL) and peripheral blood could help predict pulmonary function worsening during the clinical course of sarcoidosis. We analyzed 30 individuals with histologically proven sarcoidosis. At baseline, participants underwent pulmonary function tests (PFTs), fiberoptic bronchoscopy and radiological investigations. BAL and blood cellular profiles were obtained from all individuals and six pro-inflammatory molecules were quantified in BAL and serum. PFTs were performed at follow-up visits over a 2-year period. Using discriminant function analysis, a canonical variable was generated to optimize the accuracy of selected variables in predicting pulmonary function worsening and was validated on a subset of nine consecutive individuals with sarcoidosis. A combination of 6 markers from BAL was able to predict pulmonary function worsening in 96 % of patients [95 % confidence interval (CI) 84.4–99.81]. We validated the generated formula on a group of nine patients with sarcoidosis, obtaining 77.8 % correct classification (95 % CI 45.3–93.7). Our results show that a combinational approach could contribute to identifying individuals likely to experience pulmonary function worsening, thus helping to decide the correct therapeutic strategies.

Objectives The study aimed at prospectively evaluating the evolution of asthma control in Italy, to evaluate the reasons for lack of asthma control, perceived quality of life (QoL) and association with level of asthma control, the impact of pharmacological treatment, the number of exacerbations and the healthcare resource consumption. Methods PRISMA (PRospectIve Study on asthMA control) was an observational study performed in asthmatic patients including a cross-sectional phase and a 12-month prospective phase. Asthma control was assessed with the Asthma Control Test™ (ACT) and QoL was evaluated with EuroQoL-5D questionnaire filled in and collected during 5 clinic visits together with all the other data. Results The prospective phase included 1017 patients with uncontrolled (55.7%) or partly controlled asthma (44.3%). Out of the 739 patients evaluable after 12 months, 22.2% achieved full asthma control (ACT score = 25) and 58.7% reached a good control (ACT score: 20–24). The improvement in asthma control was associated with improved QoL and reduced hospital visits. The main reasons for lack of asthma control were comorbidities, continued exposure to irritants/triggers and poor adherence to therapy. The frequency of exacerbations was lower in patients with controlled asthma. A fixed combination therapy with an inhaled corticosteroid and a long-acting β2 agonist was reported by 77.0% of patients. A better asthma control and improved QoL were achieved with extrafine beclomethasone/formoterol compared to either budesonide/formoterol or fluticasone/salmeterol. Conclusions An improvement in asthma control and QoL can be achieved during a 1-year monitoring in a real life setting. Extrafine beclomethasone/formoterol was associated with significant benefit in terms of asthma control and QoL compared to large-particles combinations. ClinicalTrials.gov number NCT01110460.

To the Editor We read with interest the article that appeared in the Journal by De Smet and colleagues,1 who applied likelihood ratios (rather than a dichotomous interpretation) for different results intervals for 3 laboratory tests (the percentage of bronchoalveolar lavage fluid [BALF] lymphocytes, the BALF CD4/CD8 ratio, and the serum angiotensin-converting enzyme activity) to improve clinical interpretation for the diagnosis of pulmonary sarcoidosis. They also examined the allocation power of the 3 diagnostic tests combined together by means of logistic regression analysis. The authors retrospectively evaluated the data for 153 subjects (36 with diagnosed sarcoidosis and 117 control subjects with clinical suspicion of sarcoidosis, but with diagnosis of other pulmonary diseases). The combination of the 3 laboratory tests allowed exclusion of sarcoidosis in 57 (48.7%) of 117 control subjects and confirmation of the diagnosis in 12 (33%) of 36 cases of pulmonary sarcoidosis.1 We strongly agree with the authors that the common practice of applying diagnostic tests by using strict cutoff values may result in a loss of …

BACKGROUND: Hypercapnic Chronic Obstructive Pulmonary Disease (COPD) exacerbation in patients with comorbidities and multidrug therapy is complicated by mixed acid-base, hydro-electrolyte and lactate disorders. Aim of this study was to determine the relationships of these disorders with the requirement for and duration of noninvasive ventilation (NIV) when treating hypercapnic respiratory failure. METHODS: Sixty-seven consecutive patients who were hospitalized for hypercapnic COPD exacerbation had their clinical condition, respiratory function, blood chemistry, arterial blood gases, blood lactate and volemic state assessed. Heart and respiratory rates, pH, PaO(2) and PaCO(2) and blood lactate were checked at the 1st, 2nd, 6th and 24th hours after starting NIV. RESULTS: Nine patients were transferred to the intensive care unit. NIV was performed in 11/17 (64.7%) mixed respiratory acidosis-metabolic alkalosis, 10/36 (27.8%) respiratory acidosis and 3/5 (60%) mixed respiratory-metabolic acidosis patients (p = 0.026), with durations of 45.1 ± 9.8, 36.2 ± 8.9 and 53.3 ± 4.1 hours, respectively (p = 0.016). The duration of ventilation was associated with higher blood lactate (p

Neurotrophins (NTs) expression was assessed in malignant and non-malignant pleural effusions (inflammatory exudates and transudates). Enzyme-linked immunosorbent assay, in malignant exudates from small and non-small cell lung cancer (SCLC and NSCLC), detected nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), and their levels are higher as compared with inflammatory and transudative effusions. By immunoblots, in cultured cancer cells coming from malignant pleural effusions, NTs and low- and high-affinity NT receptors were detected in a percentage of SCLC and NSCLC. Proliferation assay demonstrated that BDNF significantly increased cancer cell proliferation in vitro, on the contrary, NT-3 reduced cancer cell growth rate and NGF did not modify cell growth. Moreover, NGF protects cells from death during starvation. These effects are reverted by the addition of NT receptor antagonists. Cultured cancer cells injected into the lung of immunodeficient mice generate lung tumors expressing NTs and NT receptors. These findings suggest that NTs may be able to modulate cancer cell behavior and their growth.

RV performance is difficult to evaluate, given its geometry, interrelationship with the left ventricle, and sensitivity to alterations in pulmonary pressure. This article focuses on some of the challenges related to the assessment of RV function in the setting of the RV’s unique anatomic, physiologic, conventional and newer echocardiographic aspects, and therapeutic implications. The majority of proposed methods of echocardiographic assessment of RV function are based on volumetric approximations of the RV. Such approaches have inherent limitations, first as volume-related measures such as EF are load dependent, second because of the complex geometry of the RV. The issue of RV geometry is usually overcome using geometry-independent parameters such as tricuspid annular excursion and the Tei index. The recent introduction of real-time three-dimensional echocardiography and myocardial imaging echocardiography (tissue Doppler imaging, 1D-strain and 2D-strain echocardiography) implied a great progress in echocardiography. Tissue Doppler imaging allows the quantitative assessment of RV systolic and diastolic function by means of measurement of myocardial velocities. Strain measurements have been shown to correlate well with sonomicrometry segment length measurements both in the inflow and outflow tract of the RV and under different loading conditions. Other findings have been reported in chronic and acute clinical settings. Standard and novel echocardiographic methods of assessment of RV size and performance can help clinicians in the treatment of acute and chronic RV failure and contribute to a better understanding of the peculiar chamber-related functional mechanisms in the context of ventricular interdependent independency.

Background: Acute respiratory failure (ARF) occurring during idiopathic pulmonary fibrosis (IPF) is associated with a poor prognosis. In this subset of individuals, mechanical ventilation (MV) may be required. Objectives: We analysed the characteristics of a group of IPF patients undergoing MV for ARF in order to give some indications on the supposed prognosis. Methods: Hospital records of 34 consecutive patients with IPF, who underwent MV for ARF, were retrospectively examined. Demographic data, time from diagnosis, gas exchange, Acute Physiology and Chronic Health Evaluation (APACHE) II score, ARF causes and MV failure were recorded. Results: Fifteen subjects (group A) underwent invasive MV and 19 patients (group B) non-invasive ventilation (NIV). The 2 groups were different for disease severity (APACHE II score 24.2 ± 6 vs. 19.5 ± 5.9; p = 0.01). Both ventilatory strategies temporarily increased PaO2/FiO2 as compared with spontaneous breathing (group A: 148.5 ± 52 vs. 99 ± 39, p = 0.0004; group B: 134 ± 36 vs. 89 ± 26, p = 0.0004). NIV reduced the respiratory rate (26 ± 7 vs. 36 ± 9 with spontaneous breathing; p = 0.002). Duration of MV correlated with the time of evolution of IPF (r = 0.45; p = 0.018). The in-hospital mortality rate was 85% (100% for invasive MV, 74% for NIV). Four of the 5 survivors died within 6 months from hospital discharge (range 2–6 months). Conclusions: MV does not appear to have a significant impact on the survival of patients with end-stage IPF. NIV may be useful for compassionate use, providing relief from dyspnoea and avoiding aggressive approaches.

Background In this study, we analyzed maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) values in a stable COPD population compared with normal subjects. We evaluated the possible correlation between functional maximal respiratory static pressures and functional and anthropometric parameters at different stages of COPD. Furthermore, we considered the possible correlation between airway obstruction and MIP and MEP values. Subject and methods 110 patients with stable COPD and 21 age-matched healthy subjects were enrolled in this study. Patients were subdivided according to GOLD guidelines: 31 mild, 39 moderate and 28 severe. Results Both MIP and MEP were lower in patients with severe airway impairment than in normal subjects. Moreover, we found a correlation between respiratory muscle function and some functional and anthropometric parameters: FEV1 (forced expiratory volume in one second), FVC (forced vital capacity), PEF (peak expiratory flow), TLC (total lung capacity) and height. MIP and MEP values were lower in patients with severe impairment than in patients with a slight reduction of FEV1. Conclusion The measurement of MIP and MEP indicates the state of respiratory muscles, thus providing clinicians with a further and helpful tool in monitoring the evolution of COPD.

La cavita pleurica e definita da una membrana sierosa che riveste la parete toracica e la superficie dei polmoni: la pleura parietale ricopre la superficie interna della parete toracica, il mediastino ed il diaframma, mentre la pleura viscerale avvolge la superficie del polmone e ciascun lobo, con relativo ripiegamento e doppio spessore a livello interlobare.

La ventilazione meccanica non invasiva (NIV) e largamente utilizzata per aiutare i pazienti affetti da insufficienza respiratoria acuta o cronica.

Background The methacholine (MCH) challenge test is performed to detect bronchial hyperresponsiveness in subjects suffering from asthma. It is conducted by inhaling spasmogen substances at increasing doses and measuring FEV1-PD20 variation following the bronchoconstriction evoked. Aim This paper describes a new method for MCH challenge test using pre-metered respirable powders of MCH at different doses for facilitating test execution. The availability of a series of pre-metered doses gives higher control over aerosolized dose and fine particle fraction (respirable dose), improving the accuracy and repeatability of the test. Dosimetric tests with MCH solution and pre-dosed powder challenge tests were clinically compared. Methods and materials The inhalation powders were prepared by spray drying of solutions of methacholine, mannitol and hydroxypropylmethylcellulose in which different concentrations of MCH were included. The methacholine powders prepared were carefully characterized in terms of aerodynamic properties. Results Inhalation powders containing methacholine from 12.5 to 200 μg per metered dose, having a fine particle fraction between 40 and 60%, were prepared using mannitol and cellulose polymer. Eighteen subjects (12 hyperresponsive and six normal) were subjected to both the MCH solution and powder tests in random sequence. No significant differences in FEV1 and PD20 values were found between the challenge tests performed with liquid and powder formulations of methacholine. Conclusions Powders of MCH having high respirability of the delivered doses can be prepared by spray drying. They allow for the performance of a challenge test using a dry powder inhaler. The powder dose series can be an alternative to the current dosimetric test with MCH solutions.

Background Parasympathetic nerves provide the dominant autonomic innervation of the upper and lower airways. They release acetylcholine that, activating post-junctional muscarinic receptors, causes bronchoconstriction, mucous secretion and vasodilation. Dysfunction of the upper and lower airways frequently coexist, and they appear to share key elements of pathogenesis. Objective The present study has assessed the expression and pattern of cholinergic muscarinic receptor subtypes in peripheral blood lymphocytes harvested from allergic rhinitis patients with different degree of bronchial hyperresponsiveness detected by methacholine challenge test. Methods Radioligand binding assay for determining the density of muscarinic cholinergic receptor subtypes; immunoblot analysis for assessing the characteristic of muscarinic cholinergic receptor subtype protein and immunocytochemical techniques for investigating the cellular localization of receptors. Results An increased expression of M2 and M5 receptor proteins was observed in peripheral blood lymphocytes of allergic rhinitis patients in comparison with healthy control individuals. M3 receptor subtype decreased in allergic rhinitis patients with normal or mild responses to methacholine. A trend versus a return to normal value was found in moderate and severe responders. No changes of the M4 receptor subtype were found. Conclusions and clinical implications Increase in M2 receptor expression correlated with disease severity and bronchial hyperreactivity. Changes in muscarinic cholinergic receptor expression in allergic rhinitis underline a role of cholinergic system of immune cells in allergic airway disease. Capsule summary Studies addressed to rhinitis and asthma have identified many similarities. Our results indicate that changes in peripheral blood lymphocyte muscarinic receptor expression may reflect the cholinergic involvement into allergic airway diseases.

The purpose of the current study was to compare right ventricular (RV) myocardial wall velocities (tissue Doppler imaging) and strain rate imaging (SRI) parameters with conventional echocardiographic indices evaluating RV function in chronic obstructive pulmonary disease (COPD) patients. In total, 39 patients with COPD and 22 healthy subjects were included in the current study. Seventeen patients had pulmonary artery pressure35 mmHg (group I) and 22 patients had pulmonary artery pressure35 mmHg (group II). Tissue Doppler imaging, strain and strain rate (SR) values were obtained from RV free wall (FW) and interventricular septum. Respiratory function tests were performed (forced expiratory volume in one second/vital capacity (FEV(1)/VC) and carbon monoxide diffusion lung capacity per unit of alveolar volume (D(L,CO)/V(A))). Strain/SR values were reduced in all segments of group II patients compared with group I patients and controls with lowest values at basal FW site. A significant relationship was shown between peak systolic SR at basal FW site and radionuclide RV ejection fraction. A significant relationship was shown between peak systolic SR at basal FW site and D(L,CO)/V(A) and FEV(1)/VC. In conclusion, in chronic obstructive pulmonary disease patients, strain rate imaging parameters can determine right ventricular dysfunction that is complementary to conventional echocardiographic indices and is correlated with pulmonary hypertension and respiratory function tests.

La broncopneumopatia cronica ostruttiva (BPCO) e una delle maggiori cause di morbilita e mortalita in tutto il mondo. A causa dell’elevata prevalenza e della possibilita di essere una patologia altamente invalidante, i costi della BPCO possono rappresentare un importante impegno economico e sociale per la spesa sanitaria.

Brittle asthma is a rare form of severe asthma characterized by a wide variation of Peak Expiratory Flow (PEF), in spite of heavy doses of steroides. Brittle asthmatic patients had very serious and often, life threatening, attacks. Type 1 brittle asthma is characterized by a mantained PEF variability despite therapy, and it affected mostly female, aged between 15 and 55 years. Type 1 is associated to skin prick tests positivity and food intolerance. Several studies have referred a correlation with personality disorders. The patients affected with type 1 have high morbidity, and frequently they have hospital admission for assessment and stabilitation their asthmatic condition. Type 2 brittle asthma is characterized by acute attacks that are very severe and could led to death or mechanical ventilation for respiratory insufficiency. Brittle asthma is very difficult to recognize and to treat. In type 1 brittle asthma, the therapy is based on inhaled and/or oral steroids, and beta2-agonists, used with an inhaler or with subcutaneous infusion. The patients affected with type 1 had to be nearly monitered and treated. Patients affected with type 2 brittle asthma, are mostly free by simptoms, but they have severe attacks that led them to emergency treatment. Brittle asthma is a rare form of severe asthma, that the clinicians may recognize and treat very strictly, because of high morbidity and mortality.

In the formulation of inhaled drugs for the treatment of asthma and chronic obstructive pulmonary disease (COPD), considerable attention has been devoted to new aerosol morphologies which can either enhance the local effect and/or increase the penetration through the mucus, secreted in bronchial inflammatory diseases. In diseases characterized by bronchial hypersecretion, lipophilic substances, such as corticosteroids, can be remarkably impeded in reaching their receptors, which are localized within the cytoplasm of bronchial epithelial cells. Vesicles consisting of one or more surfactant bilayers enclosing aqueous spaces, are of particular interest because they offer several advantages with regard to chemical stability, lower cost and availability of materials compared to conventional liposomes. With the purpose of carrying out research leading to an innovative formulation for lung delivery capable of permeating the mucous layer, beclomethasone dipropionate, clinically used for the treatment of asthma and COPD, was entrapped in non-phospholipid vesicles. The composition providing the highest entrapment efficiency was chosen. The vesicles obtained after jet nebulization were characterized by means of freeze-fracture microscopy and dynamic light scattering. The efficiency of this new drug delivery system was evaluated in vitro with simulated mucus by means of diffusion experiments (three compartment cell apparatus), using 0.1% mucin gel-like dispersion as a barrier to drug permeation.

Inhaled corticosteroids reduce exacerbations in patients with chronic obstructive pulmonary disease (COPD) but they do not affect disease progression. FEV1, as single parameter, showed limits in describing the heterogeneity of COPD population. Combination therapy, with long-acting Beta2-agonist and corticosteroid, showed a more beneficial effect on lung function, exacerbations, and health status than single inhaled drug. The aim of this study was to assess, in stable COPD, which stage (mild, moderate, severe) shows the best response after 12 weeks inhaled treatment, and which starting functional parameters show a correlation with the response.170 stable COPD patients (38 mild, 66 moderate, 66 severe) were enrolled. Patients received salmeterol/fluticasone 50/500 microg Metered Dose Inhaler (MDI) bid for 12 weeks. Pulmonary function tests and clinical data were performed. Results were subdivided, on functional and clinical data, in "responders (R)" and "no-responders (NR)".A FEV1 improvement (+ 12% and 200 ml) was achieved in 21 mild, 28 moderate and 17 severe COPD patients, respectively 55.3%, 45.9%, and 30.9% of each group. Statistical analysis of starting functional parameters showed a correlation with the therapeutic response for FEV1/FVC, MEF50 and DLCO/VA% (p0.05).Salmeterol/fluticasone improves FEV1% in mild and moderate more than in severe COPD patients. The study confirmed the difference in response between early and advanced stage. Starting FEV1/FVC and MEF50 were significant predictors in mild and moderate stages, and starting DLCO/VA% resulted a significant predictor in moderate and severe stages.

An important determinant of clinical outcome of a lower respiratory tract infection may be sterilization of the infected lung, which is also dependent on sustained antibacterial concentrations achieved in the lung. For this reason, recently there has been increased interest in measuring the concentration of antimicrobial agents at different potential sites of infection in the lung. Levels of antibacterials are now measured in bronchial mucosa, epithelial lining fluid (ELF) and alveolar macrophages, as well as in sputum. Penicillins and cephalosporins reach only marginal concentrations in bronchial secretions, whereas fluoroquinolones and macrolides have been shown to achieve high concentrations. The extent of penetration of different antibacterials into the bronchial mucosa is relatively high. This is also true for beta-lactams, although their tissue concentrations never reach blood concentrations. Antibacterials penetrate less into the ELF than into the bronchial mucosa, but fluoroquinolones appear to concentrate more into alveolar lavage than into bronchial mucosa. Pulmonary pharmacokinetics is a very useful tool for describing how drugs behave in the human lung, but it does not promote an understanding of the pharmacological effects of a drug. More important, instead, is the correlation between pulmonary disposition of the drug and its minimum inhibitory concentration (MIC) values for the infectious agent. The addition of bacteriological characteristics to in vivo pharmacokinetic studies has triggered a 'pharmacodynamic approach'. Pharmacodynamic parameters integrate the microbiological activity and pharmacokinetics of an anti-infective drug by focusing on its biological effects, particularly growth inhibition and killing of pathogens. Drugs that penetrate well and remain for long periods at the pulmonary site of infection often induce therapeutic responses greater than expected on the basis of in vitro data. However, although the determination of antibacterial concentrations at the site of infection in the lung has been suggested to be important in predicting the therapeutic efficacy of antimicrobial treatment during bacterial infections of the lower respiratory tract, some studies have demonstrated that pulmonary bacterial clearance is correlated more closely to concentrations in the serum than to those in the lung homogenates, probably because they better reflect antibacterial concentration in the interstitial fluid.

Spontaneously hypertensive rats represent a widely used animal model of hypertension. Altered neurotrophin regulation has been related to systemic hypertension. Lung cells synthesize and release neurotrophins(NT) which are involved in several pulmonary disturbances. Our study explored the expression of NT and their receptors using molecular biology and immunohistochemistry. Spontaneously 6-, 20- and 29- weeks hypertensive (SHR) and Wistar Kyoto rat (WKY) lungs were used. SHR and WKY lungs expressed neurotrophin and neurotrophin receptor mRNAs and protein transcripts. Age and hypertension dependent increase was clearly noticeable. Furthermore, immunohistochemistry revealed that their increase was mainly noticeable within bronchial and vascular components of the lung. Although the role of NT in sympathetic hyperinnervation and progression of systemic hypertension is a well established phenomenon, their increase in SHR lungs, strongly suggest that NT may be operative during pulmonary hypertension and in subsequent airway and pulmonary vascular remodeling.

Background: Herpes simplex viruses (HSVs) are known to cause respiratory tract infections in immunocompromised hosts and, in rare instances, in immunocompetent hosts. Numerous in vitro and in vivo studies have shown that aerosolized administration of ribavirin can potently and selectively inhibit viral replication in pulmonary disease, thereby increasing the effectiveness of acyclovir in HSV. Objective: In this case study, we reported on a 46-year-old immunocompetent woman with HSV type 1 pneumonia with bilateral pulmonary infiltrates but without mucocutaneous lesions. Methods: The diagnosis was confirmed using cytology, viral culture, and serology. Because of the persistence of fever and dyspnea, we chose an antiviral therapy. The patient received oral acyclovir and aerosolized ribavirin to improve the antiviral effectiveness of the acyclovir and to reduce the symptoms and the time to resolution of the pulmonary disease. Results: After 3 days of therapy, dyspnea and fever decreased and hypoxemia improved. After 2 weeks, computed tomography showed complete resolution of pulmonary abnormalities. The patient did not report any adverse effects. Conclusions: In our case study, we demonstrated that therapy with a combination of aerosolized ribavirin and oral acyclovir may be useful to reduce the severity of viral infection, the adverse effects, and the days of hospitalization. To our knowledge, this is the first report in the literature of the synergistic effects of the combination of aerosolized ribavirin and oral acyclovir in the treatment of an immunocompetent patient with HSV pneumonia.

Pulmonary diseases induced by drugs include bronchial asthma, pulmonary infiltration with eosinophilia, diffuse fibrosing alveolitis, vasculitis, and pleural diseases.1–4 Most such diseases recede when the drug is withdrawn, although on rare occasions the pulmonary damage is irreversible and progressive.4 5 We describe a patient with asthma referred to our respiratory diseases clinic who twice developed fever and pulmonary infiltration with eosinophilia after taking antibiotics. A 17 year old white man who has had bronchial asthma since childhood was referred to our clinic in January 2002. The patient also reported sinusitis and allergic rhinitis. Results of earlier prick tests and radioallergosorbent tests were positive for wall pellitory ( Parietaria judaica ) and grasses, and the tests resulted in a mild increase in peripheral blood eosinophil counts (0.6-0.7 × 109/l (6-7%)). His general practitioner had prescribed salbutamol as a rescue treatment. The patient did not report any allergy to drugs. In December 2001 he had reported fever (38°C), accompanied by mucopurulent nasal secretion and pain in his forehead. X ray pictures of the paranasal sinuses showed maxillary sinusitis on the right side and hypertrophy of the turbinates. The general practitioner prescribed combined amoxicillin (875 mg) and clavulanic acid (125 mg) twice daily for seven days, followed by clarithromycin (500 mg) twice daily for a further seven days. Figure 1 shows the patient's course of treatment. At the end of this treatment period the patient reported dry cough and mild dyspnoea. Chest x ray pictures showed pulmonary consolidations localised at the right apex. Fig 1 Temporal relation between the patient's course of treatment and pulmonary infiltration …

Neurotrophins (NTs) promote survival and differentiation of central and peripheral neurons, and display several activities also in non-neuronal cells. Human lungs synthesize and release NTs, which are probably involved in the pathophysiology of pulmonary disturbances. In this article the expression and anatomic localization of nerve growth factor, brain-derived neurotrophic factor, and NT-3 and of corresponding high-affinity receptors TrkA, TrkB (full-length and truncated [TR-] isoforms), TrkC, and of the low-affinity p75 receptor, were assessed in surgical samples from adult human lung by reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry. NTs and their cognate receptor mRNA and protein transcripts were detected by reverse transcriptase-polymerase chain reaction and immunoblotting, respectively, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) mRNA and corresponding protein transcripts being the most expressed. High levels of TrkB-[TR-] mRNA and of its protein transcript were also demonstrated, whereas a low expression of p75 mRNA and of corresponding protein transcript were found. Microanatomic analysis of immunohistochemical study revealed that bronchial epithelial cells were immunoreactive for different NTs, with a higher intensity of BDNF immune staining compared with other NTs, but did not express NT receptor immunoreactivity. Alveolar cells were immunoreactive for TrkA and TrkC receptor protein, but did not display immunoreactivity for NTs or other receptors investigated. Gland cells expressed NT and high-affinity NT receptor immunoreactivity, but not p75 receptor immunoreactivity. NT and low-affinity receptor immunoreactivity was observed within neurons and satellite cells of parasympathetic ganglia as well as in nerve fiber-like structures supplying the bronchopulmonary tree. An obvious immunoreactivity for NTs and NT receptor protein was also observed in intrapulmonary branches of pulmonary artery. Pulmonary lymphocytes and macrophages express nerve growth factor and high-affinity NT receptor immunoreactivity. The role of NTs in non-neuronal tissue including lung has not been clarified yet. The widespread expression of NTs and their receptors in different components of the lung suggests that these factors may contribute to regulate cell function in human lung.

Patients experiencing dyspnoea can request an additional dose of salmeterol during the dose interval for the control of their symptoms, although under treatment with salmeterol. In this study we have explored the effects on respiratory function of an additive dose of salmeterol Diskus® in 15 chronic obstructive pulmonary disease (COPD) patients in regular treatment with a conventional dose of 50 μ g salmeterol. On two different days, patients inhaled 50μ g Diskus®. After 240 min, they inhaled additional 50 μ g salmeterol Diskus® (salmeterol arm) or placebo Diskus® (placebo arm). Lung function was controlled before first drug administration and 0·5, 1, 2, 3, 4, 4·5, 6, 8, 10, and 12 h thereafter. The mean (95% Cl) peak increase in FEV1 from baseline was reached after 4 h in the salmeterol arm (0·174 L; 0·144–0204) and after 5 h (0·141 L; 0·115–0·168) in the placebo arm; after 12 h, the mean (95% Cl) increase in FEV1 from basal values was still 0·149 L (0·119–0·179) in salmeterol arm, but only 0·041 L (0·017–0·064) in placebo arm. The mean (95% Cl) FEV1 AUC0–12h for all patients were 2·01 (1·72–2·30) L when salmeterol was added and 1·30 (1·03–1·58) L when placebo was inhaled. The difference (mean; 95% Cl) between the FEV1 AUC0–12h of the two arms (0·71 L; 0·47–0·95) was statistically significant (P

Inhaled corticosteroids are recommended for long-term control of asthma in children, and nebulization simplifies administration to patients who lack hand-to-lung coordination. Information on the efficacy and safety of nebulized corticosteroids in children with mild to moderate asthma is limited, however, and comparison between corticosteroids is lacking. One hundred thirty-three patients 6 to 14 years of age with bronchial asthma were randomly assigned to receive flunisolide 500 microg or budesonide 500 microg, both administered twice daily by nebulizer for 4 weeks. Morning peak expiratory flow rate (primary efficacy endpoint) increased significantly from baseline (P

Metered dose inhalers (MDIs) which have a valve holding chamber plus a mouthpiece or mask have, in recent years, markedly improved the ease, speed and reliability of aerosol therapy for reversible airflow obstruction in adults, children and infants. MDIs, effective and easily accessible when patients are away from home, are the gold standard for the treatment of reversible airflow obstruction since they provide reliable, reproducible, effort-independent dosing, protection of their contents from environmental humidity and bacterial infection and at the same time are the most readily pocketable, efficient and least expensive aerosol therapy devices available. When combined with add-on devices they are also the most versatile delivery system because they are well suited to a variety of patients and virtually any therapeutic task. With our improved understanding of the importance of drug targeting to the site of action, the most important aspects of the relationship between particle size and drug deposition throughout the lower respiratory tract are discussed. This review also looks at add-on devices and training issues related to the proper co-ordination of drug delivery with inhalation, and reports on new technology and non-ozone depleting propellants.