Long-term home noninvasive mechanical ventilation increases systemic inflammatory response in chronic obstructive pulmonary disease: a prospective observational study.

BACKGROUND: Long-term home noninvasive mechanical ventilation (NIV) is beneficial in COPD but its impact on inflammation is unknown. We assessed the hypothesis that NIV modulates systemic and pulmonary inflammatory biomarkers in stable COPD. METHODS: Among 610 patients referred for NIV, we shortlisted those undergoing NIV versus oxygen therapy alone, excluding subjects with comorbidities or non-COPD conditions. Sputum and blood samples were collected after 3 months of clinical stability and analyzed for levels of human neutrophil peptides (HNP), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-alpha). Patients underwent a two-year follow-up. Unadjusted, propensity-matched, and pH-stratified analyses were performed. RESULTS: Ninety-three patients were included (48 NIV, 45 oxygen), with analogous baseline features. Sputum analysis showed similar HNP, IL-6, IL-10, and TNF-alpha levels (P > 0.5). Conversely, NIV group exhibited higher HNP and IL-6 systemic levels (P < 0.001) and lower IL-10 concentrations (P < 0.001). Subjects undergoing NIV had a significant reduction of rehospitalizations during follow-up compared to oxygen group (P = 0.005). These findings were confirmed after propensity matching and pH stratification. CONCLUSIONS: These findings challenge prior paradigms based on the assumption that pulmonary inflammation is per se detrimental. NIV beneficial impact on lung mechanics may overcome the potential unfavorable effects of an increased inflammatory state.

Use of discriminant analysis in assessing pulmonary function worsening in patients with sarcoidosis by a panel of inflammatory biomarkers.

OBJECTIVES AND DESIGN: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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 FEV_{1} and HNP, NE and IL-8 levels (p < 0.01), between FEV_{1}/FVC and HNP, NE and IL-8 levels (p< 0.01), and between NE enrolment levels and FEV_{1} 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.

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.

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.

Neurotrophin and neurotrophin receptor protein expression in the human lung.

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.

The protective effect of the Mediterranean diet on lung cancer.

There has been growing interest over recent years in the potential preventive role of the Mediterranean diet in the development of cardiovascular disease and cancer. The present study was designed to evaluate the relationship between the components of the Mediterranean diet and lung cancer. A hospital-based, case-control study of lung cancer was conducted on subjects aged 35+ yr living in the Lazio region and admitted to one of the main hospitals in Rome in the period from 1993 to 1996. Cases (n = 342) were patients with newly diagnosed primary lung cancer. Controls (n = 292) were recruited from departments of general surgery, orthopedics, ENT, and general medicine and were frequency matched by sex and age (+/-5 yr) to the cases. Exposure characteristics were obtained by interviewing study subjects. A self-administered food-frequency questionnaire was used. After careful control for several smoking variables, we found a protective effect for high consumption of carrots (odds ratio [OR] = 0.67, 95% confidence interval [CI] = 0.42-1.05), tomatoes (OR = 0.59, 95% CI = 0.34-1.03), white meat (OR = 0.66, 95% CI = 0.42-1.02), exclusive use of olive oil (OR = 0.67, 95% CI = 0.45-0.99), and regular consumption of sage (OR = 0.43, 95% CI = 0.29-0.65). In a multivariate model, considering all food items simultaneously, the protective effect of exclusive olive oil use and sage remained statistically significant. Our results indicate that some food items typical of the Mediterranean diet are associated with decreased lung cancer risk.

[Legionnaire's pneumonia with rhabdomyolysis and acute renal failure. A case report]. / Polmonite da Legionella pneumophila complicata da insufficienza renale acuta e rabdomiolisi.

Legionella pneumophyla is the agent responsible of Legionnaire's disease. It appears as a severe pneumonia and often requires admission in Intensive Care Unit. In literature, renal failure is reported to occur in 15 percent of Legionnaire disease and this event induce a mortality over 50% of these cases. The authors describe a case of Legionnaire's pneumonia with respiratory failure, rhabdomyolysis and acute renal failure. Patient was a female, 61 yrs old, admitted to our hospital because of fever (38 degrees-38.5 degrees C), severe respiratory failure (pH = 7.49, PaCO2 = 23.1 mmHg, PaO2 = 56.7 mmHg), oliguria (< 200 ml/24 h); chest x-rays and computed tomography (TC) showed a pneumonia at right lower lobe. Among other things, in blood analysis was noted the following values: BUN = 47 mg/dl, creatinine = 2.1 mg/dl, Na+ = 133 mmol/L, Cl- = 97 mmol/L, Ca+ = 7.2 mg/dl, K+ = 5.8 mmol/L, AST = 213 U/L, ALT = 45 U/L, LDH = 1817 U/L, CPK = 16738 U/L, CPK-MB = 229 U/L, myoglobin > 4300 ng/ml., leucocyte count = 17,500/mmc (N = 92%, L = 3%, M = 5%), positive anti Legionella IgG and IgM (IgG > 1:64, IgM > 1:96), evidence of Legionella soluble antigen in the urine analysis. Therapy with clarytromicyne (500 mg b.i.d i.v.) and rifampicin (600 mg/die i.v.) was begun; computed tomography showed after six days an improvement of pulmonary lesion but, in the following days, health status and blood analysis got worse. Patient went on antibiotics and underwent haemotherapy (Hb: 8 gr/dl), haemodialysis because of acute renal failure but healthy status worse furthermore and she died on 18th days after admission. This case point out rhabdomyolysis with acute renal failure is suggestive for Legionnaire's disease and is associated with high rate of mortality.

O6-Alkylguanine-DNA-alkyltransferase activity in peripheral leukocytes, smoking and risk of lung cancer.

The level of activity of O6-alkylguanine-DNA-alkyltransferase (AGT), a DNA repair enzyme, in blood lymphocytes may be a marker of susceptibility to lung cancer. We measured the AGT activity level, expressed as pmoles of repaired bases/mg protein, in leukocytes of 153 lung cancer cases (of whom 80 were never smokers) and 106 controls (76 never smokers) enrolled in eight centres from seven countries. Subjects were interviewed with respect to active smoking and exposure to environmental tobacco smoke (ETS). Among never smokers, the odds ratios (ORs) of lung cancer were 1.3 (95% confidence interval 0.5-3.9), 1.5 (0.6-4.1) and 1.4 (0.5-3.8) in quartiles of decreasing AGT activity level, as compared to the upper quartile (P value of test for linear trend 0.6). Corresponding ORs among smokers were 3.4 (0.9-13), 2.0 (0.5-8.3) and 0.4 (0.1-1.6) (P value of test for linear trend 0.4). No interaction was suggested between AGT activity level and either cumulative smoking or exposure to ETS. Reduced AGT activity was not clearly associated with increased lung cancer risk in either smokers or non-smokers. However, the small size of our study argues for a prudent interpretation of our results.