Gregorino Paone

Mechanical ventilation in patients with end-stage idiopathic pulmonary fibrosis

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.

Interventional endoscopy in the management of benign tracheal stenoses: definitive treatment at long-term follow-up

OBJECTIVE Interventional bronchoscopy is one of the modalities for palliation and definitive treatment of benign tracheal stenosis. There is however no general agreement on the management of this disease. Aim of this work is to define, in the largest group of patients presented in the literature, what types of tracheal stenosis are amenable to definitive treatment by interventional endoscopy. METHODS From January 1996 to June 2006 209 consecutive patients (105 men, 104 women) with benign tracheal stenosis were referred to our center. Etiology included 167 post-intubation and 34 cases of post-tracheostomy stenoses, 8 cases of other diseases. The lesions were classified into two groups: simple and complex. All but nine patients underwent interventional procedures (mechanical dilatation, laser photoresection and placement of a silicone stent). Two years follow-up was complete for all patients. RESULTS Simple stenoses (n=167) were treated by 346 endoscopic procedures (mean of 2.07 per patient), 16 stents and 1 end-to-end anastomosis. Thirty-eight granulomas were treated by 59 procedures (1.56 per patient), 97 concentrical stenoses by 228 procedures (2.35 per patient) and 32 web-like lesions with 59 operative endoscopies (1.84 per patient). Overall success rate was 96%. Among the 42 complex stenoses, 9 were immediately treated by surgical resection and the remaining 33 lesions underwent 123 endoscopic procedures (3.27 per patient), with 34 stents and 1 end-to-end anastomosis subsequent to recurrence after stent removal. In this group the success rate was 69%. CONCLUSIONS Our study shows that, after a correct classification and stratification, interventional endoscopy may have a crucial role in the treatment of tracheal stenoses. In particular, endoscopy should be considered the first choice for simple stenoses, whereas complex stenoses need a multidisciplinary approach and often require surgery.

The immune response to mycobacterial 70-kDa heat shock proteins frequently involves autoreactive T cells and is quantitatively disregulated in multiple sclerosis

Heat shock proteins (HSP) are the most conserved molecules known to date that may also function as immune targets during infection. Hence, theoretically there is a high chance of cross-reactive responses to epitopes shared by host and microbe HSP. If not properly regulated, these responses may contribute to the pathogenesis of autoimmune disease. To determine if immune responses to HSP could contribute to the pathogenesis of multiple sclerosis, we raised T lymphocyte lines specific for the purified protein derivative of Mycobacterium tuberculosis (PPD) from patients with multiple sclerosis, patients with tuberculosis and from healthy individuals. These lines were then screened for their proliferative response to a M. tuberculosis 70-kDa heat shock protein (M.tb.HSP70). The relative frequency of the recognition of highly conserved sequences of M.tb.HSP70 compared to variable ones was also assessed by mapping experiments on those PPD specific T lymphocyte lines which also recognized the mycobacterial 70-kDa heat shock protein. In patients with multiple sclerosis, we observed a significantly higher estimated frequency of PPD-specific T lines responding to M.tb.HSP70 compared to healthy individuals and patients with tuberculosis. Furthermore, mapping experiments using recombinant proteins representing mycobacterial and human HSP70 sequences and a panel of synthetic peptides encompassing the whole sequence of Mycobacterium leprae HSP70, showed that the response to conserved epitopes of HSP70 is a frequent event in each of the three conditions studied, often leading to the cross-recognition of microbial and human sequences. These findings implicate the 70-kDa heat shock proteins as potential autoantigens in multiple sclerosis.

Analysis of sputum markers in the evaluation of lung inflammation and functional impairment in symptomatic smokers and COPD patients

The pivotal role of neutrophils and macrophages in smoking-related lung inflammation and COPD development is well-established. We aimed to assess whether sputum concentrations of Human Neutrophil Peptides (HNP), Neutrophil Elastase (NE), Interleukin-8 (IL-8), and Metalloproteinase-9 (MMP-9), major products of neutrophils and macrophages, could be used to trace airway inflammation and progression towards pulmonary functional impairment characteristic of COPD. Forty-two symptomatic smokers and 42 COPD patients underwent pulmonary function tests; sputum samples were collected at enrolment, and 6 months after smoking cessation. HNP, NE, IL-8, MMP-9 levels were increased in individuals with COPD (p < 0.0001). HNP and NE concentrations were higher in patients with severe airways obstruction, as compared to patients with mild-to-moderate COPD (p = 0.002). A negative correlation was observed between FEV1 and HNP, NE and IL-8 levels (p < 0.01), between FVC1/FVC and HNP, NE and IL-8 levels (p < 0.01), and between NE enrolment levels and FEV1 decline after 2 years (p = 0.04). ROC analysis, to discriminate symptomatic smokers and COPD patients, showed the following AUCs: for HNP 0.92; for NE 0.81; for IL-8 0.89; for MMP-9 0.81; for HNP, IL-8 and MMP-9 considered together 0.981. The data suggest that the measurement of sputum markers may have an important role in clinical practice for monitoring COPD.

Discriminant analysis on small cell lung cancer and non-small cell lung cancer by means of NSE and CYFRA-21.1

A correct diagnosis of small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) is essential both for prognostic and therapeutic reasons. We used discriminant analysis as a method to optimize the discriminant power of serum tumour marker levels for differentiation between SCLC and NSCLC. A panel of serum markers, including neurone specific enolase (NSE), cytokeratin fragment antigen 21.1 (CYFRA-21.1), tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA) was obtained in 50 consecutive NSCLC and 17 SCLC. Data were analysed by the BMDP statistical program after logarithmic transformation of marker levels. The variables selected were NSE and CYFRA-21.1. Considered together, they were able to give a 97% rate of correct classification. The formula generated (canonic variable, CV) was validated on a group of seven SCLC and 22 NSCLC patients. Only two errors occurred. We therefore conclude that the canonic variable tested, based on NSE and CYFRA-21.1, provides a good discrimination between the two types of lung cancer. The method is rapid, relatively inexpensive, and based on simple serum tests.

Identification of EGFR mutations in lung sarcomatoid carcinoma

1 Anatomic Pathology Unit, San Camillo-Forlanini Hospital, Rome, Italy 2 Department of Cardiovascular and Respiratory Sciences, San Camillo-Forlanini Hospital, Rome, Italy 3 Thoracic Surgery Unit, San Camillo-Forlanini Hospital, Rome, Italy Medical Oncology Unit, San Camillo-Forlanini Hospital, Rome, Italy 5 1st Oncological Pulmonary Unit, San Camillo-Forlanini Hospital, Rome, Italy 6 2nd Oncological Pulmonary Unit, San Camillo-Forlanini Hospital, Rome, Italy

The combination of a smoking cessation programme with rehabilitation increases stop-smoking rate

OBJECTIVE AND STUDY DESIGN A parallel group study to investigate the effectiveness of a smoking cessation programme performed during routine rehabilitation practice for outpatients. PATIENTS AND METHODS The study participants comprised an intervention group of 102 consecutive smokers who underwent a smoking cessation programme in a rehabilitation centre and a control group of 101 consecutive smokers who were referred to a smoking cessation centre in a pulmonary hospital. All participants underwent physical examination,pulmonary function tests and received identical behavioural and/or pharmacological treatment. In addition, the intervention group underwent rehabilitation practice 3 times a week for 3 months. RESULTS The continuous abstinence rate at 12 months, which was validated by an expired air carbon monoxide concentration of 10 parts per million or less and a household interview, was 68% in the intervention group and 32% in the control group. Multivariable analysis showed that rehabilitation was significantly associated with smoking cessation after adjusting for years of smoking, number of cigarettes smoked,gender and treatment (odds ratio = 4.34, p < 0.001). CONCLUSION This study suggests that smoking cessation programmes during routine rehabilitation may be highly effective in helping smoking withdrawal and should be a strongly recommended component of rehabilitation practice.

Mixed Acid-Base Disorders, Hydroelectrolyte Imbalance and Lactate Production in Hypercapnic Respiratory Failure: The Role of Noninvasive Ventilation

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, PaO2 and PaCO2 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<0.001), lower pH (p = 0.016), lower serum sodium (p = 0.014) and lower chloride (p = 0.038). Hyponatremia without hypervolemic hypochloremia occurred in 11 respiratory acidosis patients. Hypovolemic hyponatremia with hypochloremia and hypokalemia occurred in 10 mixed respiratory acidosis–metabolic alkalosis patients, and euvolemic hypochloremia occurred in the other 7 patients with this mixed acid-base disorder. Conclusions Mixed acid-base and lactate disorders during hypercapnic COPD exacerbations predict the need for and longer duration of NIV. The combination of mixed acid-base disorders and hydro-electrolyte disturbances should be further investigated.

Effect of insulin on airway responsiveness in patients with type 2 diabetes mellitus: a cohort study.

Background. The correlation between low insulin levels and a decreased sensitivity of the muscarinic receptor has been shown on induced-diabetes animal models. We designed a cohort study with the aim of evaluating the effects of insulin therapy on airway responsiveness (AR) in human patients with type 2 diabetes mellitus. Methods. We enrolled 92 patients with type 2 diabetes who had switched from oral anti-diabetic therapy to treatment by insulin subcutaneous injection. Patients were administered the methacholine challenge test (MCT) at time 0 (pre-insulin therapy) and at intervals of 15, 30, 90, 180, and 360 days after insulin treatment. The decline of forced expiratory volume in 1 second (FEV1)% from baseline (Δ FEV1) in response to inhaled methacholine (MCH) was determined to assess airway hyper-responsiveness (AHR). Results. A total of 81 patients (18 women and 63 men) completed the study. Their mean age was 58 ± 7 years and the mean duration of disease was 13.5 ± 7.7 years. The mean decrease of FEV1 at pre-insulin assessment was 2.96 ± 2.6%. Compared with the pre-insulin value, a significant increase of Δ FEV1 was observed at 15, 30, and 90 days after treatment (6.25%, CI 95% 5.4 to 7.2, p = 0.0005; 7.64%, CI 95% 6.6 to 8.1, p < 0.001; 6.45%, CI 95% 5.5 to 7.3, p = 0.0004, respectively), while after 180 and 360 days AR was similar to pre-insulin values (Δ FEV1, 3.62%, CI 95% 2.7 to 3.5 and 3.11%, CI 95% 7.9 to 9.3, respectively). Conclusions. The finding of an increased AR in patients with type 2 diabetes during the first 3 months of insulin therapy may underline the importance of monitoring pulmonary function and respiratory symptoms in patients switching from oral anti-diabetic drugs to insulin therapy, especially in the subset of individuals with respiratory disorders.

Demographic Characteristics, Nicotine Dependence, and Motivation to Quit as Possible Determinants of Smoking Behaviors and Acceptability of Shocking Warnings in Italy

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 (<45 years), who are more motivated to quit (Mondors score ≥ 12), and females showed a higher effectiveness of shocking warnings to reduce tobacco consumption of, 76%, 78%, and 43%, respectively with 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.