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

1. Introduction

Noninvasive mechanical ventilation (NIV) reduces erase the need for intubation, length of in-hospital stay, and mortality rate and, therefore, represents the gold standard treatment for patients with chronic obstructive pulmonary disease (COPD) and acute hypercapnic respiratory failure [1-3].

Patients with severe COPD may develop a form of chronic hypercapnic respiratory failure that requires frequent and expensive medical interventions and significantly worsens prognosis and health-related quality of life [4, 5]. Use of NIV in patients with chronic hypercapnic respiratory failure is still under debate [6-10].

Several experimental and clinical studies demonstrated that invasive mechanical ventilation modulates pulmonary and systemic inflammatory responses in healthy [11, 12] or injured lungs [13-18], sustaining the paradigm that overexpression of the inflammatory response is related to poor outcome [19]. However, the impact of these findings in patients on NIV has never been explored. The present study aimed to examine the hypothesis that domiciliary use of NIV may affect pulmonary and systemic inflammatory response in stable COPD patients.

2. Material and Methods

The study was conducted in the Respiratory Intermediate Intensive Care Unit (RIICU) of S. Camillo-Forlanini Hospital from March 2007 to January 2010. The Institutional Review Board approved the protocol (no. 584/CE), and written informed consent was obtained from participants.

2.1. Patients. Patients with severe and very severe COPD [20], admitted for acute exacerbation and discharged from RIICU with the indication for long-term home NIV, were enrolled.

Inclusion criteria were (1) [FEV.sub.1] < 50% predicted, <20% improvement in [FEV.sub.1] following bronchodilator and a ratio [FEV.sub.1]/FVC < 0.70; (2) need for noninvasive mechanical ventilation during an episode of acute respiratory failure; and (3) clinical stability associated with symptoms of nocturnal hypoventilation and PaC[O.sub.2] > 50 mmHg measured immediately after awakening from a night without mechanical ventilation [7-10, 21].

Exclusion criteria were (1) significant comorbidities (e.g., cancer, left ventricular heart failure, and unstable angina) likely to affect survival during follow-up period; (2) psychiatric disorders that could affect the ability to undergo NIV; (3) any other chronic respiratory disease that could interfere with data analysis (e.g., fibrothorax, scoliosis, bronchiectasis, cystic fibrosis, and pulmonary fibrosis); (4) history of obstructive sleep apnoea syndrome (OSAS); (5) body mass index > 40 kg/[m.sup.2]; and (5) systemic steroids therapy.

All participants received similar in-hospital management (including an NIV trial before enrollment) and the same home pharmacological treatment (bronchodilators, anticholinergics, and inhaled corticosteroids) to achieve optimal symptoms control as recommended [20].

Among patients meeting the criteria for home NIV, we evaluated 2 subsets of individuals: a study group undergoing home NIV plus long-term oxygen therapy (LTOT) and a control group in treatment with LTOT alone, on the basis of their compliance to NIV treatment (defined as the use of ventilator for [greater than or equal to] 5 hrs/night) and/or their willingness to be trained [21].

2.2. NIV Protocol. Patients were ventilated using the pressure support ventilation (PSV) module of two ventilators (Neftis; Linde, Munich Germany or Synchrony; Philips Respironics, Andover MA, USA).

Inspiratory positive airway pressure (IPAP) was set as the maximum inspiration pressure value tolerated by patients, able to ensure an exhaled tidal volume of 6 mL/kg (measured body weight). Expiratory positive airway pressure (EPAP) between 2 and 8 cm[H.sub.2]O was applied. A back up respiratory rate of 12 breaths/min was set. Oxygen was added to ventilator at a flow able to reach a target Sa[O.sub.2] [greater than or equal to] 90%. PSV was delivered using either nasal or full face mask based on patient comfort.

2.3. Study Evaluations. Four weeks after discharge, a research nurse reached all participants by phone to ascertain their live/dead status and to inquire about the use of NIV (hours per day). After 3 months, surviving patients, free from exacerbations for at least 4 weeks, were asked to return to the hospital for arterial blood gas measurements (ABL 800, Radiometer, Copenhagen) and assessment of pulmonary function tests (PFTs) (Quark PFT Cosmed, Pavona, Italy) [22] and to collect sputum and blood samples. COPD exacerbation was defined following guidelines [23].

Bronchodilator responsiveness to inhaled 400 [micro]g of salbutamol was measured and postbronchodilator values were used [20]. The number of hospital admissions during the previous 2 years was also collected.

Self-assessed smoking cessation was validated by determination of carboxyhemoglobin (COHb) concentration in blood gas analysis and confirmed by interviews with household members [24].

Subsequently, participants entered a 2-year follow-up with regular clinical evaluations carried out every 2 months; hospital admittances number and survival rate were finally recorded.

2.4. Blood and Sputum Processing and Analyses. Fasting peripheral blood was collected and samples were stored at -80[degrees]C until protein quantification assays. Sputum induction was obtained using 4.5% sodium chloride solution given as two nebulisations each lasting for 7 minutes [25]. Samples were collected and processed within 2 hours. Briefly, sputum was incubated for 15 minutes with four times its weight of freshly prepared 0.1% dithiothreitol (DTT) in Hank's Buffered Salt Solution (HBSS). After incubation the volume of HBSS was doubled and incubated for 5 additional minutes. The suspension was then filtered through a 50 [micro]m nylon gauze to remove mucus and debris and centrifuged at 2000 rpm for 10 minutes. Total cell counts were obtained by using a haemocytometer and cell viability was determined by trypan blue exclusion method. Sputum samples adequacy was evaluated following the literature [26]. Samples were then frozen at -80[degrees]C. Concentrations of human neutrophil peptides (HNP), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-alpha) in sputum and blood samples were quantified by commercial sandwich ELISA following manufacturer instructions (R & D Minneapolis, MN, and HbtCell Sciences, Canton, MA, USA).

2.5. Statistical Analysis. Continuous variables are reported as median (1st-3rd quartile) and categorical variables are reported as n (%). Continuous variables were compared with Mann-Whitney test for unpaired variables and Wilcoxon test for paired variables, and categorical variables were compared with the chi-squared test (or Fisher's exact test when appropriate). Correlation was appraised with Spearman test. Survival curves were computed with the Kaplan-Meier method and compared with the log-rank test. Propensity score matched-pairs were obtained with a nonparsimonious logistic regression model and used for adjusted analyses. Statistical significance was set at the 2-tailed 0.05 level, and P values unadjusted for multiplicity are reported throughout.

3. Results

A total of 610 consecutive individuals were referred to our center for an episode of acute respiratory failure; in the population of 459 COPD patients, stage GOLD III and IV, 156 subjects did not satisfy the inclusion criteria because of the presence of significant comorbidities (54.5%), a BMI > 40 kg/[m.sup.2] (28.2%), and psychiatric disorders that could affect ability to undergo NIV (17.3%). Among the 303 eligible individuals, 208 subjects were recruited in the study (Figure 1). Blood and sputum samples were obtained from 48 individuals in NIV + LTOT and 45 patients in LTOT alone.

Patients' baseline demographic data and clinical characteristics are summarized in Table 1. No differences (demographics, smoking history, comorbidities, therapy, pulmonary function, and gas exchange) were observed between study and control group, before and after matching.

Average NIV setting in the study group was IPAP 18.5 [+ or -] 2.66 cm[H.sub.2]O and EPAP 3.9 [+ or -] 1 cm[H.sub.2]O. Mean daily use of ventilator was 7.4 [+ or -] 1.3 hours.

3.1. Inflammatory Biomarkers Measurements. Blood and sputum levels of TNF-alpha, IL-6, IL-10, and HNP observed in the 2 groups are shown in Table 2. Systemic concentrations of HNP and IL-6 were significantly higher, while IL-10 concentrations were lower in patients undergoing home NIV compared to subjects in long-term oxygen therapy (P < 0.001); no differences were found in TNF-alpha levels. These findings were confirmed after matching analysis. No significant differences were observed in sputum markers levels between the 2 groups of individuals before and following matching analysis.

Participants were further stratified into 2 subsets according to pH values at initial evaluation (pH < 7.35 or pH > 7.35). The clinical characteristics of the 2 subpopulations are shown in Table 3: no differences in demographics, comorbidities, treatment, lung function, and gas exchange were detected. Systemic higher HNP and IL-6 and lower IL10 concentrations were observed in subjects with pH < 7.35 undergoing NIV; similar observations were obtained in individuals with pH > 7.35, with the exception of IL-10 (no significant differences). Sputum biomarkers levels were similar between the two subsets of patients (Table 4).

No correlations were found between biomarkers levels and pulmonary function tests (P > 0.05); NIV settings analysis pointed out an inverse association between HNP sputum concentrations and EPAP (rho = -0.31, P = 0.03).

Sputum and blood biomarkers levels were similar between smokers and nonsmokers (all P > 0.05).

No differences were found in the prevalence of individuals with frequent exacerbations ([greater than or equal to] 2 in the year prior to baseline evaluation) between study and control groups (46% versus 40%, resp., P = 0.5). IL-10 sputum levels were significantly decreased in frequent exacerbators as compared to individuals with a low number of exacerbations (5 [3-15] versus 15 [5-23], P = 0.02).

3.2. Hospitalizations and Survival Rates. Median follow-up period was the same for both groups of participants (24 months). During the follow-up period, hospitalization rates were significantly different between the two groups (1 [0-2] for NIV + LTOT and 2.0 [1-4] for LTOT, P = 0.01) with a significant reduction in hospital admissions after enrollment in NIV + LTOT group (2.5 [1-4] versus 1 [0-2], P < 0.01) and no differences in LTOT subset (2 [1-3] versus 2 [1-4], P = 0.4).

Survival rate was similar between the two groups (27.1% and 22.2%; subjects died in the study and control group, resp., P = 0.6), as well as survival time, which appeared to be comparable between the 2 subsets of individuals (22.6 [20.7-24.5] months versus 24.1 [22.5-25.8] months, resp.). In both groups deaths were mostly caused by acute or chronic respiratory failure (34% in NIV + LTOT and 33% in LTOT group), heart failure (22% and 17%, resp.), or pulmonary infection (11% in NIV + LTOT and 17% in LTOT group).

Follow-up results are shown in Table 5.

4. Discussion

The present study shows that systemic concentration of inflammatory mediators is higher in patients treated with long-term home noninvasive mechanical ventilation than in patients treated with domiciliary oxygen supplementation only.

While the role of NIV in the management of COPD acute exacerbations is well established [1-3], the impact of long-term home mechanical ventilation is still a matter of debate and its rationale is controversial. Kolodziej et al. concluded that NIV use in patients with severe stable COPD may improve gas exchange, dyspnoea, exercise tolerance, work of breathing, health-related quality of life, and functional status with a significant reduction of the hospitalization rate [7].

Mc Evoy and coworkers showed that NIV was associated with survival improvement while no changes in arterial blood gas analysis, pulmonary function, or hospitalization rates were observed [6]. Recently, a "high intensity" NIV approach was shown to be effective in decreasing PaC[O.sub.2], improving lung function and global inspiratory muscle strength [27, 28].

The ability of conventional invasive mechanical ventilation to initiate or worsen pulmonary and systemic inflammatory response has been demonstrated in experimental and clinical settings. These data led to the hypothesis that mechanical ventilation (MV) may contribute to worsen or cause lung injury [13, 17, 18] and may be related to the development of multiple organ failure. Although current research concerning ventilator induced lung injury (VILI) is largely based on positive pressure ventilation delivered via endotracheal tube, these principles may be equally relevant to noninvasive pressure ventilation [29].

While very few studies have evaluated the role of NIV in pulmonary and systemic inflammation in animal models and humans [30, 31], to the best of our knowledge, this is the first report aimed at mutually analyzing local and systemic inflammatory responses in patients undergoing long-term NIV for stable COPD.

We found a significant increase in IL-6 and HNP systemic concentrations together with a noteworthy lower amount of IL-10 in patients undergoing long-term NIV.

It is important to underline that the systemic levels of proinflammatory molecules we found in our report, although increased in NIV population, were by far lower than those reported in studies involving patients with invasive ventilation-associated lung injury [12, 18] and in the range of concentrations observed in individuals with stable COPD [32].

Cytokines are low-molecular weight proteins that may initiate and orchestrate inflammatory response to different stimuli. They are produced by airway epithelial cells, alveolar macrophages, neutrophils, and lymphocytes. Concentration of IL-6 has been shown to be increased during positive mechanical ventilation-associated lung injury and its role in VILI is well established [18, 33, 34].

HNPs represent more than 30% of azurophilic granules content and stimulate alveolar macrophages to release IL8, leukotriene B4 (LTB4), and TNF-alpha [35, 36] which may determine a vicious circle contributing to perpetuate inflammation.

The balance between proinflammatory (IL-6) and anti-inflammatory (IL-10) cytokines is crucial in regulating the immune response, contributing to the dampening of the otherwise massive inflammatory response in the lower respiratory tract [37].

In order to obtain a more homogeneous sample and to avoid the profound impact that COPD exacerbations could have had on lung and systemic inflammatory responses, we excluded from the evaluation subjects with any symptom or sign of exacerbation [38]. In addition, because of the pivotal role of pH in COPD patients with respiratory failure, we further stratified participants using a pH cut-off value of 7.35 [6, 8]. The differences between systemic markers concentrations were maintained, confirming the overall evaluation. The clinical follow-up evaluation after 2 years, although not showing differences in survival between the 2 groups, pointed out a significant decrease in the rate of hospital admissions in the study group during the follow-up period, in line with other reports [7, 8].

Our study has several limitations. First, it is an observational cohort study. Accordingly, the lack of randomization remains a key flaw of this work, given the inherent risks of selection, performance, attrition, and adjudication bias. Nonetheless, carefully designed observational studies may reduce the risk of imprecise and inaccurate estimates [39]. To minimize the risk of overestimating or underestimating biologic and clinical effects, we relied for both groups on established indications criteria for the use of NIV in stable COPD [6, 8, 10, 21]. In addition, the choice of medical treatment and ventilatory settings did not significantly change over the period of interest in our institution, providing a common management ground for our comparisons. Moreover, in order to reduce potential confounding factors, propensity score matching and pH-based stratified analyses were performed to compensate for nonrandom assignment to treatments. Second, due to the high number of exacerbations observed during the study period, we did not achieve a time course collection of biomarkers from an adequate number of patients. Therefore, we could not evaluate over time the effects of mechanical ventilation on the modifications of markers concentrations.

Our study is the first analyzing biomarkers levels in COPD patients undergoing long-term home NIV. We reckon that our major finding is that patients with NIV have a significant increase in systemic inflammation as compared to a control group undergoing LTOT alone. Remarkably, follow-up analysis showed a significant lower hospitalization in the study group as compared to control group. Therefore this data seems to suggest that, at least in patients with stable COPD, the activation of proinflammatory mediators related to mechanical ventilation is not linked to an unfavorable clinical outcome. A similar role of a proinflammatory response necessary for adaptive cardiac remodeling observed in the cardiovascular system may explain our preliminary findings [40-42].

In conclusion, this preliminary study provides original information regarding the relationship between NIV and inflammatory response in patients with chronic hypercapnic respiratory failure. Our data might challenge the view that activation of a proinflammatory signal is per se related to a worse clinical outcome. In this context we cannot rule out that the beneficial impact of NIV on respiratory mechanics (reduction of hyperinflation, work of breathing, and respiratory muscles overload) may overcome the potential unfavorable effects of an increased inflammatory state.

Further studies are required to confirm these preliminary observations.

Abbreviations

NIV:        Noninvasive mechanical ventilation
COPD:       Chronic obstructive pulmonary disease
LTOT:       Long-term oxygen therapy
OSAS:       Obstructive sleep apnea syndrome
HNPs:       Human neutrophil peptides
IL-10:      Interleukin-10
IL-6:       Interleukin-6
TNF-alpha:  Tumor necrosis factor-alpha.


http://dx.doi.org/10.1155/2014/503145

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.

Acknowledgment

This work was supported by PRIN, year 2007--Protocol no. 2007E4SCMR to Giacomo Frati.

References

[1] L. Brochard, D. Isabey, J. Piquet et al., "Reversal of acute exacerbation of chronic obstructive lung disease by inspiratory assistance with a face mask," The New England Journal of Medicine, vol. 323, no. 22, pp. 1523-1530, 1990.

[2] O. K. Plant, J. L. Owen, and M. W. Elliott, "Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial," The Lancet, vol. 355, no. 9219, pp. 1931-1935, 2000.

[3] J. V. Lightowler, J. A. Wedzicha, M. W. Elliott, and F. S. Ram, "Non-invasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: cochrane systematic review and metaanalysis," British Medical Journal, vol. 326, no. 7382, pp. 185-187, 2003.

[4] T. A. Seemungal, G. C. Donaldson, E. A. Paul, J. C. Bestall, D. J. Jeffries, and J. A. Wedzicha, "Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease," American Journal of Respiratory and Critical Care Medicine, vol. 157, no. 5, pp. 1418-1422, 1998.

[5] S. D. Sullivan, S. D. Ramsey, and T. A. Lee, "The economic burden of COPD," Chest, vol. 117, no. 2, pp. 5S-9S, 2000.

[6] R. D. McEvoy, R. J. Pierce, D. Hillman et al., "Nocturnal noninvasive nasal ventilation in stable hypercapnic COPD: a randomised controlled trial," Thorax, vol. 64, no. 7, pp. 561-566, 2009.

[7] M. A. Kolodziej, L. Jensen, B. Rowe, and D. Sin, "Systematic review of noninvasive positive pressure ventilation in severe stable COPD," European Respiratory Journal Supplement, vol. 30, no. 2, pp. 293-306, 2007

[8] E. Clini, C. Sturani, A. Rossi et al., "The Italian multicentre study on noninvasive ventilation in chronic obstructive pulmonary disease patients," European Respiratory Journal Supplement, vol. 20, no. 3, pp. 529-538, 2002.

[9] C. Casanova, B. R. Celli, L. Tost et al., "Long-term controlled trial of nocturnal nasal positive pressure ventilation in patients with severe COPD," Chest, vol. 118, no. 6, pp. 1582-1590, 2000.

[10] D. Hess, "The growing role of noninvasive ventilation in patients requiring prolonged mechanical ventilation," Respiratory Care, vol. 57, no. 6, pp. 900-920, 2012.

[11] I. Tsangaris, M. E. Lekka, E. Kitsiouli, S. Constantopoulos, and G. Nakos, "Bronchoalveolar lavage alterations during prolonged ventilation of patients without acute lung injury," European Respiratory Journal Supplement, vol. 21, no. 3, pp. 495-501, 2003.

[12] H. Wrigge, J. Zinserling, F. Stuber et al., "Effects of mechanical ventilation on release of cytokines into systemic circulation in patients with normal pulmonary function," Anesthesiology, vol. 93, no. 6, pp. 1413-1416, 2000.

[13] V. M. Ranieri, F. Giunta, P. M. Suter, and A. S. Slutsky, "Mechanical ventilation as a mediator of multisystem organ failure in acute respiratory distress syndrome," The Journal of the American Medical Association, vol. 284, no. 1, pp. 43-44, 2000.

[14] M. B. Amato, C. S. Barbas, D. M. Medeiros et al., "Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome," The New England Journal of Medicine, vol. 338, no. 6, pp. 347-354, 1998.

[15] T. Whitehead and A. S. Slutsky, "The pulmonary physician in critical care * 7: ventilator induced lung injury," Thorax, vol. 57, no. 7, pp. 635-642, 2002.

[16] D. Dreyfuss, P. Soler, G. Basset, and G. Saumon, "High inflation pressure pulmonary edema. Respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure," American Review of Respiratory Disease, vol. 137, no. 5, pp. 1159-1164, 1988.

[17] L. N. Tremblay and A. S. Slutsky, "Pathogenesis of ventilator-induced lung injury: trials and tribulations," American Journal of Physiology: Lung Cellular and Molecular Physiology, vol. 288, no. 4, pp. L596-L598, 2005.

[18] V. M. Ranieri, P. M. Suter, C. Tortorella et al., "Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial," The Journal of the American Medical Association, vol. 282, no. 1, pp. 54-61, 1999.

[19] P. E. Parsons, M. A. Matthay, L. B. Ware, and M. D. Eisner, "Elevated plasma levels of soluble TNF receptors are associated with morbidity and mortality in patients with acute lung injury," American Journal of Physiology: Lung Cellular and Molecular Physiology, vol. 288, no. 3, pp. L426-L431, 2005.

[20] K. F. Rabe, S. Hurd, A. Anzueto et al., "Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary," American Journal of Respiratory and Critical Care Medicine, vol. 176, no. 6, pp. 532-555, 2007.

[21] G.-C. Funk, M.-K. Breyer, O. C. Burghuber et al., "Long-term non-invasive ventilation in COPD after acute-on-chronic respiratory failure," Respiratory Medicine, vol. 105, no. 3, pp. 427-434, 2011.

[22] P. H. Quanjer, G. J. Tammeling, J. E. Cotes, O. F. Pedersen, R. Peslin, and J. C. Yernault, "Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society," European Respiratory Journal Supplement, vol. 16, pp. 5-40, 1993.

[23] B. R. Celli and P. J. Barnes, "Exacerbations of chronic obstructive pulmonary disease," European Respiratory Journal Supplement, vol. 29, no. 6, pp. 1224-1238, 2007

[24] P. Whincup, O. Papacosta, L. Lennon, and A. Haines, "Carboxyhaemoglobin levels and their determinants in older British men," BMC Public Health, vol. 6, article 189, 2006.

[25] P. L. Paggiaro, P. Chanez, O. Holz et al., "Sputum induction," European Respiratory Journal Supplement, vol. 20, no. 37, supplement, pp. 3S-8S, 2002.

[26] M. L. Bartoli, E. Bacci, S. Carnevali et al., "Quality evaluation of samples obtained by spontaneous or induced sputum: comparison between two methods of processing and relationship with clinical and functional findings," Journal of Asthma, vol. 39, no. 6, pp. 479-486, 2002.

[27] W. Windisch, M. Haenel, J. H. Storre, and M. Dreher, "High-intensity non-invasive positive pressure ventilation for stable hypercapnic COPD," International Journal of Medical Sciences, vol. 6, no. 2, pp. 72-76, 2009.

[28] M. Dreher, J. H. Storre, C. Schmoor, and W. Windisch, "High-intensity versus low-intensity non-invasive ventilation in patients with stable hypercapnic COPD: a randomised crossover trial," Thorax, vol. 65, no. 4, pp. 303-308, 2010.

[29] A. S. Slutsky and V. M. Ranieri, "Ventilator-induced lung injury," The New England Journal of Medicine, vol. 369, no. 22, pp. 2126-2136, 2013.

[30] J.-C. Borel, R. Tamisier, J. G. Bermejo et al., "Noninvasive ventilation in mild obesity hypoventilation syndrome: a randomized controlled trial," Chest, vol. 141, no. 3, pp. 692-702, 2012.

[31] C. Gessner, R. Scheibe, M. Wotzel et al., "Exhaled breath condensate cytokine patterns in chronic obstructive pulmonary disease," Respiratory Medicine, vol. 99, no. 10, pp. 1229-1240, 2005.

[32] B. Celli, N. Locantore, J. Yates et al., "Inflammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary disease," American Journal of Respiratory and Critical Care Medicine, vol. 185, no. 10, pp. 1065-1072, 2012.

[33] F. B. Plotz, H. A. Vreugdenhil, A. S. Slutsky, J. Zijlstra, C. J. Heijnen, and H. van Vught, "Mechanical ventilation alters the immune response in children without lung pathology," Intensive Care Medicine, vol. 28, no. 4, pp. 486-492, 2002.

[34] F. Stuber, H. Wrigge, S. Schroeder et al., "Kinetic and reversibility of mechanical ventilation-associated pulmonary and systemic inflammatory response in patients with acute lung injury," Intensive Care Medicine, vol. 28, no. 7, pp. 834-841, 2002.

[35] L. T. Spencer, G. Paone, P. M. Krein, F. N. Rouhani, J. Rivera-Nieves, and M. L. Brantly, "Role of human neutrophil peptides in lung inflammation associated with [[alpha].sub.1]-antitrypsin deficiency," American Journal of Physiology: Lung Cellular and Molecular Physiology, vol. 286, no. 3, pp. L514-L520, 2004.

[36] G. Paone, G. Lucantoni, A. Leone et al., "Human neutrophil peptides stimulate tumor necrosis factor-[alpha] release by alveolar macrophages from patients with sarcoidosis," Chest, vol. 135, no. 2, pp. 586-587, 2009.

[37] W. Y. Park, R. B. Goodman, K. P. Steinberg et al., "Cytokine balance in the lungs of patients with acute respiratory distress syndrome," American Journal of Respiratory and Critical Care Medicine, vol. 164, no. 10, part 1, pp. 1896-1903, 2001.

[38] N. Soler, C. Agustl, J. Angrill, J. P. de la Bellacasa, and A. Torres, "Bronchoscopic validation of the significance of sputum purulence in severe exacerbations of chronic obstructive pulmonary disease," Thorax, vol. 62, no. 1, pp. 29-35, 2007.

[39] E. von Elm, D. G. Altman, M. Egger, S. J. Pocock, P. C. Gotzsche, and J. P Vandenbroucke, "The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies," Annals of Internal Medicine, vol. 147, no. 8, pp. 573-577, 2007.

[40] D. Carnevale, G. Cifelli, G. Mascio et al., "Placental growth factor regulates cardiac inflammation through the tissue inhibitor of metalloproteinases-3/tumor necrosis factor-[alpha]-converting enzyme axis: crucial role for adaptive cardiac remodeling during cardiac pressure overload," Circulation, vol. 124, no. 12, pp. 1337-1350, 2011.

[41] M. Neri, V Fineschi, M. di Paolo et al., "Cardiac oxidative stress and inflammatory cytokines response after myocardial infarction," Current Vascular Pharmacology. In press.

[42] I. M. Seropian, S. Toldo, B. W. van Tassell, and A. Abbate, "Anti-inflammatory strategies for ventricular remodeling following ST-segment elevation acute myocardial infarction," Journal of the American College of Cardiology, vol. 63, no. 16, pp. 1593-1603, 2014.

Gregorino Paone (1,2), Vittoria Conti (3), Giuseppe Biondi-Zoccai (4), Elena De Falco (4), Isotta Chimenti (4), Mariangela Peruzzi (4), Corrado Mollica (2), Gianluca Monaco (2), Gilda Giannunzio (2), Giuseppe Brunetti (2), Giovanni Schmid (5), V. Marco Ranieri (6), and Giacomo Frati (4,7)

(1) Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiological, and Geriatric Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy

(2) Department of Respiratory Diseases, San Camillo-Forlanini Hospital, Circonvallazione Gianicolense 87, 00152 Rome, Italy

(3) Department of Respiratory Diseases, IRCCS San Raffaele Pisana, Via della Pisana 235, 00163 Rome, Italy

(4) Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100 Latina, Italy

(5) IRCCS Fondazione Don Carlo Gnocchi-Onlus, Via Maresciallo Caviglia 30, 00194 Rome, Italy

(6) Department of Anesthesia and Intensive Care Medicine, S. Giovanni Battista Molinette Hospital, University of Turin, Corso Dogliotti 14,10126 Turin, Italy

(7) Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Via Atinense 18, Pozzilli, 86077 Isernia, Italy

Correspondence should be addressed to Gregorino Paone; rpaone1023@yahoo.com

Received 11 March 2014; Revised 8 May 2014; Accepted 11 May 2014; Published 25 May 2014

Academic Editor: Vittorio Fineschi

TABLE 1: Baseline features *.

                       Long-term         Noninvasive      P value
                     oxygen therapy      ventilation

Before matching          N = 45             N = 48

Age (years)            72 (66-78)         69 (64-74)       0.091

Male gender            23 (51.1%)         21 (43.8%)       0.477

Diabetes               7 (15.6%)          7 (14.6%)         1.0
mellitus

Arterial               36 (80.0%)         46 (95.8%)       0.018
hypertension

Smoking status          4 (8.9%)           3 (6.2%)        0.709

Cor pulmonale          11 (24.4%)         11 (22.9%)        1.0

Long-acting             2 (4.4%)           1 (2.1%)        0.609
muscarinic
agent only

Long-acting                0               1 (2.1%)         1.0
beta2 agonist
only

Inhalatory                 0                  0             1.0
corticosteroid
only

Long-acting            6 (13.3%)           4 (8.3%)        0.515
beta2 agonist
plus inhalatory
corticosteroid

Long-acting            37 (82.2%)         41 (85.4%)       0.676
muscarinic
agent, plus
long-acting
beta2 agonist
and inhalatory
corticosteroid

Oxygen therapy       2.0 (2.0-3.0)      2.5 (2.0-3.0)      0.059
(L/min)

[FEV.sub.1] (%      30.0 (23.5-34.5)   27.5 (23.0-34.8)    0.467
predicted)

FVC (%              52.0 (47.0-63.0)   50.0 (42.8-57.0)    0.120
predicted)

[FEV.sub.1]/        54.0 (48.0-61.5)   57.0 (50.0-63.5)    0.385
FVC (%)

pH                  7.36 (7.34-7.38)   7.35 (7.34-7.37)    0.125

P[O.sub.2] (mm      72.2 (62.5-84.4)   72.4 (66.6-80.9)    0.756
Hg)

PC[O.sub.2] (mm     55.6 (48.7-61.9)   57.8 (52.9-67.3)    0.086
Hg)

Oxygen              93.6 (92.8-95.4)   93.9 (92.6-96.1)    0.732
saturation (%)

White blood         8.00 (6.85-9.59)   7.73 (6.25-8.48)    0.227
cells (cell
number x
[10.sup.3]/mL)

Polymorphonuclear   71.3 (66.0-75.4)   66.4 (60.4-73.1)    0.020
neutrophils (%)

Procalcitonin            <0.05              <0.05           1.0
(ng/mL)

After matching           N = 30             N = 30

Age (years)            71(66-77)          70 (64-73)       0.390

Male gender            15 (50.0%)         16 (53.3%)       0.796

Diabetes               4 (13.3%)          3 (10.0%)         1.0
mellitus

Arterial               29 (96.7%)         29 (96.7%)        1.0
hypertension

Smoking status          2 (6.7%)           1 (3.3%)         1.0

Cor pulmonale          8 (26.7%)          9 (30.0%)        0.774

Long-acting             1 (3.3%)           1 (3.3%)         1.0
muscarinic
agent only

Long-acting                0                  0             1.0
beta2 agonist
only

Inhalatory                 0                  0             1.0
corticosteroid
only

Long-acting            4 (13.3%)           2 (6.7%)        0.671
beta2 agonist
plus inhalatory
corticosteroid

Long-acting            25 (83.3%)         27 (90.0%)       0.706
muscarinic
agent, plus
long-acting
beta2 agonist
and inhalatory
corticosteroid

Oxygen therapy       3.0 (2.0-4.3)      2.3 (2.0-3.0)      0.837
(L/min)

[FEV.sub.1] (%      27.5 (22.8-32.5)   28.0 (23.8-35.0)    0.695
predicted)

FVC (%              51.5 (44.8-61.5)   50.0 (45.0-57.0)    0.351
predicted)

[FEV.sub.1]/FVC     54.0 (47.0-61.3)   59.0 (50.0-64.3)    0.228
(%)

pH                  7.36 (7.33-7.37)    735 (7.34-736)     0.466

P[O.sub.2] (mm      68.5 (62.4-80.1)   73.3 (68.0-81.0)    0.176
Hg)

PC[O.sub.2] (mm     55.7 (48.7-61.4)   57.8 (54.2-64.1)    0.139
Hg)

Oxygen              93.4 (92.8-94.8)   94.1 (93.0-96.0)    0.228
saturation (%)

White blood         8.03 (6.68-9.83)   7.72 (5.73-8.38)    0.154
cells (cell
number x
[10.sup.3]/mL)

Polymorphonuclear   72.2 (67.2-75.5)   66.0 (60.2-70.7)    0.011
neutrophils (%)

Procalcitonin            <0.05              <0.05           1.0
(ng/mL)

* reported as median (1st-3rd quartile) or n (%) and compared
with Mann-Whitney U-test, chi-squared test, or Fisher's exact
test.

TABLE 2: Blood and sputum biomarkers concentrations *.

                                                Long-term
                                              oxygen therapy

Before matching                                   N = 45

Sputum
  Human neutrophil peptides ([micro]g/mL)    34.5 (33.0-35.3)
  Interleukin-6 (pg/mL)                      40.0 (19.0-51.5)
  Interleukin-10 (pg/mL)                      14.0 (6.0-24.0)
  Tumor necrosis factor-alpha (pg/mL)        32.0 (22.0-110.0)
Blood
  Human neutrophil peptides ([micro]g/mL)      3.3 (1.1-9.8)
  Interleukin-6 (pg/mL)                        3.7 (2.9-6.0)
  Interleukin-10 (pg/mL)                       70 (5.4-8.0)
  Tumor necrosis factor-alpha (pg/mL)          7.0 (3.0-9.0)
Sputum/blood ratio
  Human neutrophil peptides                   10.5 (3.7-35.1)
  Interleukin-6                               7.0 (4.6-14.4)
  Interleukin-10                               2.6 (1.0-3.8)
  Tumor necrosis factor-alpha                 7.8 (3.7-14.0)
After matching                                    N = 30
Sputum
  Human neutrophil peptides ([micro]g/mL)    34.0 (33.0-35.6)
  Interleukin-6 (pg/mL)                      42.5 (28.3-52.3)
  Interleukin-10 (pg/mL)                      14.0 (3.8-24.3)
  Tumor necrosis factor-alpha (pg/mL)        29.0 (20.0-72.5)
Blood
  Human neutrophil peptides ([micro]g/mL)     3.2 (0.9-10.5)
  Interleukin-6 (pg/mL)                        3.5 (2.9-6.1)
  Interleukin-10 (pg/mL)                       6.5 (5.0-8.0)
  Tumor necrosis factor-alpha (pg/mL)          6.5 (4.5-8.3)
Sputum/blood ratio
  Human neutrophil peptides                   11.0 (3.5-41.0)
  Interleukin-6                               8.5 (5.0-16.1)
  Interleukin-10                               2.6 (1.1-4.0)
  Tumor necrosis factor-alpha                 4.9 (2.5-13.4)

                                                Noninvasive
                                                ventilation

Before matching                                   N = 48

Sputum
  Human neutrophil peptides ([micro]g/mL)    34.0 (32.3-36.0)
  Interleukin-6 (pg/mL)                      41.9 (18.0-68.5)
  Interleukin-10 (pg/mL)                      5.0 (4.0-20.0)
  Tumor necrosis factor-alpha (pg/mL)        49.0 (30.0-99.0)
Blood
  Human neutrophil peptides ([micro]g/mL)     10.8 (7.9-11.7)
  Interleukin-6 (pg/mL)                       8.2 (6.1-10.9)
  Interleukin-10 (pg/mL)                       3.2 (0.8-6.7)
  Tumor necrosis factor-alpha (pg/mL)         8.0 (5.0-10.0)
Sputum/blood ratio
  Human neutrophil peptides                    3.3 (2.9-5.2)
  Interleukin-6                                3.9 (2.0-8.2)
  Interleukin-10                               3.5 (0.9-6.6)
  Tumor necrosis factor-alpha                 8.0 (3.8-15.0)
After matching                                   N = 30
Sputum
  Human neutrophil peptides ([micro]g/mL)    33.6 (31.5-36.0)
  Interleukin-6 (pg/mL)                      40.9 (16.0-65.5)
  Interleukin-10 (pg/mL)                      5.5 (3.0-23.5)
  Tumor necrosis factor-alpha (pg/mL)        47.0 (27.0-105.0)
Blood
  Human neutrophil peptides ([micro]g/mL)     10.9 (7.2-11.7)
  Interleukin-6 (pg/mL)                       8.7 (6.3-18.3)
  Interleukin-10 (pg/mL)                       1.0 (0.7-6.0)
  Tumor necrosis factor-alpha (pg/mL)         8.0 (4.6-11.8)
Sputum/blood ratio
  Human neutrophil peptides                    3.2 (2.9-5.7)
  Interleukin-6                                3.9 (1.5-8.4)
  Interleukin-10                               4.2 (1.4-8.8)
  Tumor necrosis factor-alpha                 8.5 (3.6-15.2)

                                             P value

Before matching

Sputum
  Human neutrophil peptides ([micro]g/mL)     0.787
  Interleukin-6 (pg/mL)                       0.275
  Interleukin-10 (pg/mL)                      0.092
  Tumor necrosis factor-alpha (pg/mL)         0.412
Blood
  Human neutrophil peptides ([micro]g/mL)    < 0.001
  Interleukin-6 (pg/mL)                      < 0.001
  Interleukin-10 (pg/mL)                     < 0.001
  Tumor necrosis factor-alpha (pg/mL)         0.122
Sputum/blood ratio
  Human neutrophil peptides                  < 0.001
  Interleukin-6                               0.010
  Interleukin-10                             < 0.001
  Tumor necrosis factor-alpha                 0.803
After matching
Sputum
  Human neutrophil peptides ([micro]g/mL)     0.563
  Interleukin-6 (pg/mL)                       0.734
  Interleukin-10 (pg/mL)                      0.347
  Tumor necrosis factor-alpha (pg/mL)         0.068
Blood
  Human neutrophil peptides ([micro]g/mL)     0.003
  Interleukin-6 (pg/mL)                      < 0.001
  Interleukin-10 (pg/mL)                     < 0.001
  Tumor necrosis factor-alpha (pg/mL)         0.216
Sputum/blood ratio
  Human neutrophil peptides                   0.002
  Interleukin-6                               0.004
  Interleukin-10                              0.042
  Tumor necrosis factor-alpha                 0.344

* reported as median (1st-3rd quartile) or n (%) and compared with
Mann-Whitney U test, chi-squared test, or Fisher exact test.

TABLE 3: Baseline features according to pH *.

                       Long-term         Noninvasive      P value
                     oxygen therapy      ventilation

pH < 7.35                N = 14             N =17

Age (years)            69 (64-78)         67 (62-72)       0.426

Male gender            6 (42.9%)          10 (58.8%)       0.376

Diabetes               3 (21.4%)          3 (17.6%)         1.0
mellitus

Arterial               12 (85.7%)         17 (100%)        0.196
hypertension

Smoking status          1 (7.1%)           1 (5.9%)         1.0

Cor pulmonale          2 (14.3%)          3 (17.6%)         1.0

Long-acting            2 (14.3%)           1 (5.9%)        0.576
muscarinic
agent only

Long-acting                0                  0             1.0
beta2 agonist
only

Inhalatory                 0                  0             1.0
corticosteroid
only

Long-acting                0                  0             1.0
beta2 agonist
plus inhalatory
corticosteroid

Long-acting            12 (85.7%)         16 (94.1%)       0.576
muscarinic
agent plus
long-acting
beta2 agonist
and inhalatory
corticosteroid

Oxygen therapy       2.3 (2.0-3.3)      2.0 (2.0-3.0)      0.672

[FEV.sub.1] (%      30.5 (25.0-32.5)   24.0 (20.0-31.0)    0.209
predicted)

FVC (%              56.5 (43.8-61.5)   48.0 (40.5-52.0)    0.108
predicted)

[FEV.sub.1]/FVC     51.0 (46.3-61.3)   55.0 (45.5-62.5)    0.633
(%)

pH                  732 (7.31-7.33)    7.33 (7.31-7.34)    0.382

P[O.sub.2] (mm      73.6 (66.3-83.9)   72.0 (66.0-79.0)    0.648
Hg)

PC[O.sub.2] (mm     64.2 (55.1-675)    67.9 (59.2-71.0)    0.266
Hg)

Oxygen              94.4 (93.2-95.6)   93.3 (91.5-95.4)    0.275
saturation (%)

White blood         7.67 (6.74-9.47)   7.60 (5.45-8.46)    0.147
cells (cell
number x
[10.sup.3]/mL)

Polymorphonuclear   69.9 (67.2-73.6)   66.4 (61.6-72.3)    0.137
neutrophils (%)

Procalcitonin            < 0.05             <0.05           1.0
(ng/mL)

pH [greater              N = 31             N = 31
than or equal
to] 7.35

Age (years)            72 (66-76)         70 (65-74)       0.139

Male gender            17 (54.8%)         11 (35.5%)       0.126

Diabetes               4 (12.9%)          4 (12.9%)         1.0
mellitus

Arterial               24 (77.4%)         29 (93.5%)       0.147
hypertension

Smoking status          3 (9.7%)           2 (6.5%)         1.0

Cor pulmonale          9 (29.0%)          8 (25.8%)        0.776

Long-acting                0                  0             1.0
muscarinic
agent only

Long-acting                0               1 (3.2%)         1.0
beta2 agonist
only

Inhalatory                 0                  0             1.0
corticosteroid
only

Long-acting            6 (19.4%)          4 (12.9%)        0.490
beta2 agonist
plus inhalatory
corticosteroid

Long-acting            25 (80.6%)         25 (80.6%)        1.0
muscarinic
agent plus
long-acting
beta2 agonist
and inhalatory
corticosteroid

Oxygen therapy       2.0 (2.0-2.5)      3.0 (2.0-4.0)      0.015

[FEV.sub.1] (%      30.0 (23.0-37.0)   31.0 (26.0-36.0)    0.893
predicted)

FVC (%              51.0 (48.0-64.0)   52.0 (46.0-60.0)    0.490
predicted)

[FEV.sub.1]/FVC     57.0 (49.0-62.0)   59.0 (51.0-65.0)    0.434
(%)

pH                  7.37 (7.36-739)    7.36 (7.35-7.38)    0.013

P[O.sub.2] (mm      71.8 (62.4-85.2)   74.0 (67.0-83.9)    0.593
Hg)

PC[O.sub.2] (mm     53.8 (46.8-57.5)   56.0 (50.6-60.3)    0.141
Hg)

Oxygen              93.3 (92.6-95.5)   94.1 (93.0-96.7)    0.239
saturation (%)

White blood         8.04 (6.84-9.68)   7.80 (6.71-8.87)    0.573
cells (cell
number x
[10.sup.3]/mL)

Polymorphonuclear   72.1 (64.9-75.6)   65.6 (60.2-73.9)    0.077
neutrophils (%)

Procalcitonin            <0.05              <0.05           1.0
(ng/mL)

* reported as median (1st-3rd quartile) or n (%) and compared with
Mann-Whitney U-test, chi-squared test, or Fisher's exact test.

TABLE 4: Blood and sputum biomarkers concentrations according to pH *.

                                                 Long-term
                                              oxygen therapy

pH < 7.35                                         N = 14

Sputum
  Human neutrophil peptides ([micro]g/mL)    33.2 (30.8-35.3)
[-0.5pt] Interleukin-6 (pg/mL)               40.0 (19.8-56.0)
  Interleukin-10 (pg/mL)                      11.0 (5.3-18.0)
  Tumor necrosis factor-alpha (pg/mL)        56.0 (26.5-113.8)
Blood
  Human neutrophil peptides ([micro]g/mL)      2.3 (1.1-9.6)
  Interleukin-6 (pg/mL)                        4.7 (2.9-6.9)
  Interleukin-10 (pg/mL)                       7.0 (5.9-8.5)
  Tumor necrosis factor-alpha (pg/mL)          6.5 (4.8-8.3)
Sputum/blood ratio
  HNP                                         16.8 (3.6-39.3)
  Interleukin-6                               7.9 (5.0-13.6)
  Interleukin-10                               1.7 (0.8-2.9)
  Tumor necrosis factor-alpha                 9.5 (3.6-16.0)

pH [greater than or equal to] 7.35                N = 31

Sputum
  Human neutrophil peptides ([micro]g/mL)    34.5 (33.0-35.4)
  Interleukin-6 (pg/mL)                      40.0 (16.0-50.0)
  Interleukin-10 (pg/mL)                      14.0 (6.0-25.0)
  Tumor necrosis factor-alpha (pg/mL)        30.0 (20.0-110.0)
Blood
  Human neutrophil peptides ([micro]g/mL)     3.5 (1.0-10.5)
  Interleukin-6 (pg/mL)                        3.5 (2.9-6.0)
  Interleukin-10 (pg/mL)                       7.0 (1.0-8.0)
  Tumor necrosis factor-alpha (pg/mL)         7.0 (2.0-10.0)
Sputum/blood ratio
  HNP                                         9.4 (3.5-35.1)
  Interleukin-6                               6.7 (3.8-15.0)
  Interleukin-10                               3.0 (1.1-4.4)
  Tumor necrosis factor-alpha                 7.8 (3.7-14.0)

                                                Noninvasive
                                                ventilation

pH < 7.35                                          N = 17

Sputum
  Human neutrophil peptides ([micro]g/mL)    33.0 (30.0-36.0)
[-0.5pt] Interleukin-6 (pg/mL)               50.0 (23.0-75.5)
  Interleukin-10 (pg/mL)                      5.0 (4.0-24.0)
  Tumor necrosis factor-alpha (pg/mL)        45.0 (22.0-115.0)
Blood
  Human neutrophil peptides ([micro]g/mL)     11.0 (5.4-11.5)
  Interleukin-6 (pg/mL)                       7.0 (4.0-18.4)
  Interleukin-10 (pg/mL)                       1.0 (0.7-6.0)
  Tumor necrosis factor-alpha (pg/mL)         8.0 (3.4-10.0)
Sputum/blood ratio
  HNP                                         3.1 (2.8-10.6)
  Interleukin-6                               7.5 (2.7-11.9)
  Interleukin-10                               4.1 (0.9-9.0)
  Tumor necrosis factor-alpha                 8.5 (2.9-17.5)

pH [greater than or equal to] 7.35                 N = 31

Sputum
  Human neutrophil peptides ([micro]g/mL)    34.0 (33.0-37.2)
  Interleukin-6 (pg/mL)                      35.0 (16.0-58.0)
  Interleukin-10 (pg/mL)                      5.0 (4.0-18.0)
  Tumor necrosis factor-alpha (pg/mL)        50.0 (31.0-96.0)
Blood
  Human neutrophil peptides ([micro]g/mL)     9.4 (7.8-11.8)
  Interleukin-6 (pg/mL)                       8.4 (6.3-10.6)
  Interleukin-10 (pg/mL)                       3.6 (0.9-7.0)
  Tumor necrosis factor-alpha (pg/mL)         8.0 (5.4-14.8)
Sputum/blood ratio
  HNP                                          3.7 (2.9-5.4)
  Interleukin-6                                3.3 (1.8-7.5)
  Interleukin-10                               3.3 (0.8-5.0)
  Tumor necrosis factor-alpha                 6.1 (3.9-12.5)

                                             P value

pH < 7.35

Sputum
  Human neutrophil peptides ([micro]g/mL)     0.952
[-0.5pt] Interleukin-6 (pg/mL)                0.311
  Interleukin-10 (pg/mL)                      0.499
  Tumor necrosis factor-alpha (pg/mL)         0.858
Blood
  Human neutrophil peptides ([micro]g/mL)     0.040
  Interleukin-6 (pg/mL)                       0.049
  Interleukin-10 (pg/mL)                      0.001
  Tumor necrosis factor-alpha (pg/mL)         0.617
Sputum/blood ratio
  HNP                                         0.032
  Interleukin-6                               0.475
  Interleukin-10                              0.068
  Tumor necrosis factor-alpha                 0.953

pH [greater than or equal to] 7.35

Sputum
  Human neutrophil peptides ([micro]g/mL)     0.677
  Interleukin-6 (pg/mL)                       0.592
  Interleukin-10 (pg/mL)                      0.113
  Tumor necrosis factor-alpha (pg/mL)         0.207
Blood
  Human neutrophil peptides ([micro]g/mL)     0.002
  Interleukin-6 (pg/mL)                      <0.001
  Interleukin-10 (pg/mL)                      0.097
  Tumor necrosis factor-alpha (pg/mL)         0.095
Sputum/blood ratio
  HNP                                         0.002
  Interleukin-6                               0.010
  Interleukin-10                              0.751
  Tumor necrosis factor-alpha                 0.683

* reported as median (1st-3rd quartile) or n (%) and compared with
Mann-Whitney U-test, chi-squared test, or Fisher's exact test.

TABLE 5: Clinical results *.

                                    Long-term         Noninvasive
                                  oxygen therapy      ventilation

Overall population
Before matching                       N = 45             N = 48
  Follow-up (months)             24.0 (21.0-25.5)   24.0 (24.0-24.0)
  Prior hospitalizations          2.0 (1.0-3.0)      2.5 (1.0-4.0)
  Subsequent hospitalizations     2.0 (1.0-4.0)       1.0 (0-2.0)
  All hospitalizations             4.0 (2.0-70)      4.0 (2.0-6.8)
  Death                             10 (22.2%)         13 (27.1%)
After matching                        N = 30             N = 30
  Follow-up (months)             24.0 (22.5-25.0)   24.0 (22.5-24.0)
  Prior hospitalizations          3.0 (2.0-3.0)      2.0 (1.0-3.3)
  Subsequent hospitalizations     2.5 (1.0-4.0)       1.0 (0-1.3)
  All hospitalizations            5.0 (3.0-7.0)      3.0 (1.8-5.0)
  Death                             7 (23.3%)          9 (30.0%)
Excluding cross-overs
Before matching                       N = 38             N = 48
  Follow-up (months)             24.0 (16.5-25.0)   24.0 (24.0-24.0)
  Prior hospitalizations          2.0 (1.0-3.0)      2.5 (1.0-4.0)
  Subsequent hospitalizations     2.0 (1.0-3.0)       1.0 (0-2.0)
  All hospitalizations            4.0 (2.0-5.3)      4.0 (2.0-6.8)
  Death                             9 (23.7%)          13 (27.1%)
After matching                        N = 26             N = 30
  Follow-up (months)             24.5 (22.5-25.0)   24.0 (22.5-24.0)
  Prior hospitalizations          2.0 (2.0-3.0)      2.0 (1.0-3.3)
  Subsequent hospitalizations     2.0 (1.0-3.0)       1.0 (0-1.3)
  All hospitalizations            4.5 (3.0-6.0)      3.0 (1.8-5.0)
  Death                             6 (23.1%)          9 (30.0%)

                                 P value

Overall population
Before matching
  Follow-up (months)              0.190
  Prior hospitalizations          0.498
  Subsequent hospitalizations     0.005
  All hospitalizations            0.536
  Death                           0.587
After matching
  Follow-up (months)              0.198
  Prior hospitalizations          0.564
  Subsequent hospitalizations    <0.001
  All hospitalizations            0.021
  Death                           0.976
Excluding cross-overs
Before matching
  Follow-up (months)              0.325
  Prior hospitalizations          0.282
  Subsequent hospitalizations     0.024
  All hospitalizations            0.885
  Death                           0.720
After matching
  Follow-up (months)              0.168
  Prior hospitalizations          0.980
  Subsequent hospitalizations     0.001
  All hospitalizations            0.082
  Death                           0.560

* reported as median (1st-3rd quartile) or n (%) and compared with
Mann-Whitney U-test, chi-squared test, or Fisher's exact test.
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Title Annotation:Research Article
Author:Paone, Gregorino; Conti, Vittoria; Biondi-Zoccai, Giuseppe; De Falco, Elena; Chimenti, Isotta; Peruz
Publication:Mediators of Inflammation
Article Type:Clinical report
Date:Jan 1, 2014
Words:7351
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