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Increased Sympathetic Nerve Activity in COPD is Associated with Morbidity and Mortality

Chronic obstructive lung disease (COPD) is a major cause of comorbidity and mortality. Systemic effects, such as sympathetic activation, might contribute to progression and severity of the disease.

Objectives : This study investigated whether increased sympathetic activity is associated with increased long-term morbidity and mortality with COPD.

Methods : Following a baseline registration of muscle sympathetic nerve activity (MSNA), 21 COPD patients and 21 matched healthy control subjects were contacted after a mean follow-up period of 7 years. Information about the number of hospitalizations during follow-up was obtained from patients who were still alive. Information about the time of death was collected from relatives of the deceased and local registration offices. The primary endpoint was the comparison of MSNA in living patients without hospitalizations versus MSNA in the patients who died or had at least one hospitalization due to exacerbation of COPD.

Results : At baseline, MSNA was significantly increased, whereas forced expiratory volume in 1 s and arterial oxygen tension (PaO2) were significantly decreased in patients compared with controls. MSNA was significantly higher in COPD patients who had reached the combined endpoint of hospitalization or death during follow-up (n = 12) compared with patients who were still alive at follow-up and had not been hospitalized (n = 8): 60.3 ± 15.8 (SD) bursts/min versus 40.5 ± 17.5 bursts/min; p = 0.022.

Conclusions : Our data suggest that sympathetic activation is related to adverse outcome in COPD. Although this finding has to be replicated in larger studies, it implies that neurohumoral activation could be a potential therapeutic target in COPD.

 

Increased Platelet Binding to Circulating Monocytes in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia and its prognosis is poor. Epidemiological evidence suggests an association of IPF with vascular disease and thrombotic tendency, which may be related to platelet activation.

Methods :Platelet–monocyte adhesion in peripheral blood was examined by flow cytometry in patients with IPF (n = 19), interstitial lung disease (ILD) other than IPF (n = 9), and control subjects without pulmonary fibrosis (n = 14). Expression of platelet activation markers P-selectin (CD62P), PSGL-1 (CD162), and CD40 ligand (CD40L) on leukocytes and platelets were studied. Plasma concentrations of soluble P-selectin and CD40L were measured by ELISA.

Results : Significantly elevated levels of platelet–monocyte binding were found in patients with IPF (35.6 ± 4.34 % [mean ± SEM]) compared with patients with non-IPF ILD (23.5 ± 3.68 %) and non-ILD control subjects (16.5 ± 2.26 %; P < 0.01). There was a trend towards increased divalent cation-independent platelet–monocyte binding in IPF (6.0 ± 0.77 % [mean ± SEM]) compared with non-IPF ILD (4.3 ± 1.38 %) and control subjects without ILD (3.1 ± 1.75 %; P = 0.058). There was no differential surface expression of platelet activation markers on subsets of leukocytes or platelets. Plasma concentrations of CD40L and soluble P-selectin did not differ between IPF and control subjects. Platelet–monocyte binding had no significant correlation with percent predicted TLco or FVC.

Conclusions : Platelet–monocyte binding is increased in IPF, suggesting increased platelet activation. This conjugation is predominantly calcium-dependent, but there may be more calcium-independent adhesion in IPF. These findings support further research into the role of platelet activation in IPF.

Prognostic factors of Pneumocystis jirovecii pneumonia in patients without HIV infection.

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Prognostic factors of Pneumocystis jirovecii pneumonia in patients without HIV infection.

J Infect. 2014 Mar 4;

Authors: Kim SJ, Lee JW, Cho YJ, Park YS, Lee CH, Yoon HI, Lee SM, Yim JJ, Lee JH, Yoo CG, Lee CT, Kim YW, Han SK, Kim HB, Park JS

Abstract
OBJECTIVES: The incidence of Pneumocystis jirovecii pneumonia (PCP) in patients without HIV infection (non-HIV PCP) has been increasing along with the increased use of chemotherapeutic agents and immunosuppressants, but the prognostic factors of non-HIV PCP remain unclear. This study aimed to identify the prognostic factors of non-HIV PCP.
METHODS: Immunocompromised patients without HIV infection who were diagnosed and treated for PCP were included. The PCP diagnosis was based on positive direct fluorescent antibody (DFA) or polymerase chain reaction (PCR) results and compatible clinical symptoms and radiological findings.
RESULTS: In total, 372 non-HIV patients with positive PCP DFA or PCR findings were screened and 173 were included. Univariate analysis indicated that age, smoking, chronic lung disease or hematologic malignancy, chemotherapeutic agents, high alveolar-arterial oxygen gradient (D[A-a]O2), C-reactive protein, albumin, blood urea nitrogen (BUN), CMV antigenemia, combined bacteremia, high percentage of neutrophils and rate of co-infection in BAL fluid, and mechanical ventilator care were related to the prognosis of non-HIV PCP. Multivariate analysis revealed that high D(A-a)O2, combined bacteremia, increased BUN and preexisting lung disease were indicators of a poor prognosis.
CONCLUSIONS: High D(A-a)O2, combined bacteremia, increased BUN and preexisting lung disease were independent factors of poor prognosis in non-HIV PCP patients.

PMID: 24607411 [PubMed - as supplied by publisher]

The global burden of respiratory disease-Impact on child health.

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The global burden of respiratory disease-Impact on child health.

Pediatr Pulmonol. 2014 Mar 9;

Authors: Zar HJ, Ferkol TW

Abstract
Respiratory disease is the major cause of mortality and morbidity worldwide, with infants and young children especially susceptible. The spectrum of disease ranges from acute infections to chronic non-communicable diseases. Five respiratory conditions dominate-acute respiratory infections, chronic obstructive pulmonary disease, asthma, tuberculosis (TB), and lung cancer. Pneumonia remains the predominant cause of childhood mortality, causing nearly 1.3 million deaths each year, most of which are preventable. Asthma is the commonest non-communicable disease in children. Pediatric TB constitutes up to 20% of the TB caseload in high incidence countries. Environmental exposures such as tobacco smoke, indoor air pollution, and poor nutrition are common risk factors for acute and chronic respiratory diseases. Pediatric and adult respiratory disease is closely linked. Early childhood respiratory infection or environmental exposures may lead to chronic disease in adulthood. Childhood immunization can effectively reduce the incidence and severity of childhood pneumonia; childhood immunization is also effective for reducing pneumonia in the elderly. The Forum of International Respiratory Societies (FIRS), representing the major respiratory societies worldwide, has produced a global roadmap of respiratory diseases, Respiratory Disease in the World: Realities of Today-Opportunities for Tomorrow. This highlights the burden of respiratory diseases globally and contains specific recommendations for effective strategies. Greater availability and upscaled implementation of effective strategies for prevention and management of respiratory diseases is needed worldwide to improve global health and diminish the current inequities in health care worldwide. Pediatr Pulmonol. © 2014 Wiley Periodicals, Inc.

PMID: 24610581 [PubMed - as supplied by publisher]

Assessment of Circulating microRNAs in Plasma of Lung Cancer Patients.

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Assessment of Circulating microRNAs in Plasma of Lung Cancer Patients.

Molecules. 2014;19(3):3038-54

Authors: Fortunato O, Boeri M, Verri C, Conte D, Mensah M, Suatoni P, Pastorino U, Sozzi G

Abstract
Lung cancer is the most common cause of cancer deaths worldwide and numerous ongoing research efforts are directed to identify new strategies for its early detection. The development of non-invasive blood-based biomarkers for cancer detection in its preclinical phases is crucial to improve the outcome of this deadly disease. MicroRNAs (miRNAs) are a new promising class of circulating biomarkers for cancer detection and prognosis definition, but lack of consensus on data normalization methods for circulating miRNAs and the critical issue of haemolysis, has affected the identification of circulating miRNAs with diagnostic potential. We describe here an interesting approach for profiling circulating miRNAs in plasma samples based on the evaluation of reciprocal miRNA levels measured by quantitative Real-Time PCR. By monitoring changes of plasma miRNA-ratios, it is possible to assess the deregulation of tumor-related miRNAs and identify signatures with diagnostic and prognostic value. In addition, to avoid bias due to the release of miRNAs from blood cells, a miRNA-ratios signature distinguishing haemolyzed samples was identified. The method described was validated in plasma samples of lung cancer patients, but given its reproducibility and reliability, could be potentially applied for the identification of diagnostic circulating miRNAs in other diseases.

PMID: 24619302 [PubMed - in process]

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