BMC Pulmonary Medicine - Latest Articles

Plasma CC16 levels are associated with development of ALI/ARDS in patients with ventilator-associated pneumonia: a retrospective observational study

Rogier Determann — 2009-12-03T00:00:00Z

Background Despite consensus criteria, diagnosing acute lung injury, or its more severe form acute respiratory distress syndrome (ALI/ARDS) remains challenging. Adding objective measures, such as plasma levels of biological markers could facilitate recognition of ALI/ARDS. This study was designed to assess and compare the diagnostic accuracy of biological markers for ALI/ARDS with ventilator-associated pneumonia (VAP).Methods We performed serial measurements of Clara cell protein (CC16), soluble receptor for advanced glycation end products (sRAGE), surfactant protein D (SP-D) and Krebs von den Lungen (KL-6) in plasma of patients with VAP and mechanically ventilated control patients without VAP. ALI/ARDS was diagnosed using the criteria of the North-American European consensus conference.Results Thirty-seven patients were enrolled - 22 patients with VAP and 15 control patients. Ten patients with pneumonia met the ALI/ARDS consensus criteria. Control patients never met these criteria. Plasma CC16 had a good diagnostic capacity for ALI/ARDS as shown by the receiver operating characteristic curve with an area under the curve of 0.91 (95% confidence interval (CI) 0.79 - 1.00; p < 0.001). Identification of ALI/ARDS patients by sudden increases in plasma CC16 of 30% or more yielded a sensitivity of 90% and a specificity of 92%. Of note, levels of CC16 increased 2 days before ALI/ARDS diagnosis. A cut-off level of 50 ng/ml SP-D yielded a specificity of 100% while the sensitivity was 70%. The area under the curve for SP-D was 0.80 (95% CI 0.58 - 1.00; p = 0.02). The diagnostic accuracies of KL-6 and sRAGE were low.Conclusions Plasma CC16 seems a potential biological marker for ALI/ARDS in patients with VAP. Plasma levels of sRAGE, SP-D and KL-6 have limited discriminative power for diagnosing ALI/ARDS in VAP.

Comparative analysis of selected exhaled breath biomarkers obtained with two different temperature-controlled devices

Frank Hoffmeyer — 2009-11-30T00:00:00Z

Background: The collection of exhaled breath condensate (EBC) is a suitable and non-invasive method for evaluation of airway inflammation. Several studies indicate that the composition of the condensate and the recovery of biomarkers are affected by physical characteristics of the condensing device and collecting circumstances. Additionally, there is an apparent influence of the condensing temperature, and often the level of detection of the assay is a limiting factor. The ECoScreen2 device is a new, partly single-use disposable system designed for studying different lung compartments. Methods: EBC samples were collected from 16 healthy non-smokers by using the two commercially available devices ECoScreen2 and ECoScreen at a controlled temperature of -20degreesC. EBC volume, pH, NOx, LTB4, PGE2, 8-isoprostane and cys-LTs were determined. Results: EBC collected with ECoScreen2 was less acidic compared to ECoScreen. ECoScreen2 was superior concerning condensate volume and detection of biomarkers, as more samples were above the detection limit (LTB4 and PGE2) or showed higher concentrations (8-isoprostane). However, NOx was detected only in EBC sampled by ECoScreen. Conclusions: ECoScreen2 in combination with mediator specific enzyme immunoassays may be suitable for measurement of different biomarkers. Using this equipment, patterns of markers can be assessed that are likely to reflect the complex pathophysiological processes in inflammatory respiratory disease.

Evaluation of psychological and physiological predictors of fatigue in patients with COPD

Agnieszka Lewko — 2009-10-21T00:00:00Z

Background: Fatigue in COPD impairs functional status; however there are few studies examining mechanistic pathways of this symptom. The aims of this study are to compare fatigue between COPD patients and healthy age-matched subjects, and to identify predictors of fatigue in COPD. Methods: Seventy four COPD patients, mean age 69.9 (49-87) yrs, mean (SD) % predicted FEV1 46.5 (20.0) % and FEV1/FVC ratio 0.45 (0.13) and 35 healthy subjects, mean age 67.1 (50-84) yrs completed the Multidimensional Fatigue Inventory (MFI 20). Patients' assessment included Depression (HADS), lung function, BMI, muscle strength, incremental shuttle walk test (ISWT), exercise oxygen saturation (SpO2), Borg breathlessness (CR-10) and exertion (RPE). Serum level of Interleukin 6 (IL-6) was recorded. Differences in MFI 20 between groups were examined and predictors of fatigue identified using logistic regression. Results: Significant differences (p < 0.01) were found between the COPD and healthy subjects for all MFI 20 dimensions. There were significant differences when classified according to GOLD and dyspnoea stages for selected dimensions only. Predictors of General Fatigue were depression, muscle strength and end SpO2 (R2 = .62); of Physical Fatigue: depression, % predicted FEV1, ISWT and age (R2 = .57); Reduced Activity: % predicted FEV1, BMI and depression (R2 = .36); Reduced Motivation: RPE, depression and end SpO2 (R2 = .37) and Mental Fatigue: depression and end SpO2 (R2 = .38). Conclusion: All dimensions of fatigue were higher in COPD than healthy aged subjects. Predictive factors differ according to the dimension of fatigue under investigation. COPD-RF is a multi component symptom requiring further consideration.

Association of the TLR4 Asp299Gly polymorphism with lung function in relation to body mass index

Punam Pahwa — 2009-09-21T00:00:00Z

Background: Previous studies have shown conflicting results for the association between TLR4 polymorphism (Asp299Gly) and lung function. We investigated the influence of TLR4 Asp299Gly, a polymorphism, on lung function in a community population. Methods: In 2003, a cross-sectional survey was conducted to assess the respiratory health of residents living in and around the town of Humboldt, Saskatchewan, Canada. There were 2090 adults age 18-79 years who completed a questionnaire that included a medical and smoking history, as well as socio-economic and lifestyle variables. Genetic information and lung function test measurements were available on 1725 subjects (754 males and 971 females) of the 2090 respondents. These subjects were selected for further analysis to investigate the association between TLR4 Asp299Gly genotype and forced expiratory volume in the first second in liters (FEV1), forced vital capacity in liters (FVC), FEV1/FVC ratio, and forced expiratory flow rate in liters/second (FEF25-75). Multivariable linear regression analysis was used to investigate associations. Results: Adjusted mean values of FEV1 and FVC were significantly different between TLR4 wild type and TLR4 variant groups [Mean ± S.E.: (TLR4 wild type - FEV1: 3.18 ± 0.02, FVC: 3.95 ± 0.03; TLR4 variant - FEV1: 3.31 ± 0.06, FVC: 4.14 ± 0.07)]. Based on multivariable regression analysis, we observed that body mass index (BMI) was associated with decreased FEV1/FVC ratio and FEF25-75 in TLR4 variant group but not in wild type group. Conclusion: BMI may modify the associations of TLR4 Asp299Gly polymorphism with FEV1/FVC ratio and FEF25-75.

Protective effect of geranylgeranylacetone, an inducer of heat shock protein 70, against drug-induced lung injury/fibrosis in an animal model

Takayoshi Fujibayashi — 2009-09-16T00:00:00Z

Background: To determine whether oral administration of geranylgeranylacetone (GGA), a nontoxic anti-ulcer drug that is an inducer of heat shock protein (HSP) 70, protects against drug-induced lung injury/fibrosis in vivo. Methods: We used a bleomycin (BLM)-induced lung fibrosis model in which mice were treated with oral 600 mg/kg of GGA before and after BLM administration. Inflammation and fibrosis were evaluated by histological scoring, hydroxyproline content in the lung and inflammatory cell count, and quantification by ELISA of macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage fluid. Apoptosis was evaluated by the TUNEL method. The induction of HSP70 in the lung was examined with western blot analysis and its localization was determined by immunohistochemistry. Results: We confirmed the presence of inflammation and fibrosis in the BLM-induced lung injury model and induction of HSP70 by oral administration of GGA. GGA prevented apoptosis of cellular constituents of lung tissue, such as epithelial cells, most likely related to the de novo induction of HSP70 in the lungs. GGA-treated mice also showed less fibrosis of the lungs, associated with the findings of suppression of both production of MIP-2 and inflammatory cell accumulation in the injured lung, compared with vehicle-treated mice. Conclusion: GGA had a protective effect on drug-induced lung injury/fibrosis. Disease-modifying antirheumatic drugs such as methotrexate, which are indispensable for the treatment of rheumatoid arthritis, often cause interstitial lung diseases, an adverse event that currently cannot be prevented. Clinical use of GGA for drug-induced pulmonary fibrosis might be considered in the future.

Efficacy and safety of tigecycline versus levofloxacin for community-acquired pneumonia

Cristina Tanaseanu — 2009-09-09T00:00:00Z

Background: Tigecycline, an expanded broad-spectrum glycylcycline, exhibits in vitro activity against many common pathogens associated with community-acquired pneumonia (CAP), as well as penetration into lung tissues that suggests effectiveness in hospitalized CAP patients. The aim of the present study was to compare the efficacy and safety of intravenous (IV) tigecycline with IV levofloxacin in hospitalized adults with CAP. Methods: In this prospective, double-blind, non-inferiority phase 3 trial, eligible patients with a clinical diagnosis of CAP supported by radiographic evidence were stratified by Fine Pneumonia Severity Index and randomized to tigecycline or levofloxacin for 7-14 days of therapy. Co-primary efficacy endpoints were clinical response in the clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure (Day 10-21 post-therapy). Results: Of the 428 patients who received at least one dose of study drug, 79% had CAP of mild-moderate severity according to their Fine score. Clinical cure rates for the CE population were 88.9% for tigecycline and 85.3% for levofloxacin. Corresponding c-mITT population rates were 83.7% and 81.5%, respectively. Eradication rates for Streptococcus pneumoniae were 92% for tigecycline and 89% for levofloxacin. Nausea, vomiting, and diarrhoea were the most frequently reported adverse events. Rates of premature discontinuation of study drug or study withdrawal because of any adverse event were similar for both study drugs. Conclusion: These findings suggest that IV tigecycline is non-inferior to IV levofloxacin and is generally well-tolerated in the treatment of hospitalized adults with CAP.Trial registrationNCT00081575

Impact of patient characteristics, education and knowledge on emergency room visits in patients with asthma and COPD: a descriptive and correlative study

Margareta Emtner — 2009-09-07T00:00:00Z

Background: Asthma and COPD are major health problems and an extensive burden for the patient and the health care system. Patient education has been recommended, but the influence on knowledge and health outcomes is not fully examined. Our aims were to compare patient characteristics, education and knowledge in patients who had an emergency room (ER) visit, to explore factors related to disease knowledge, and to investigate patient characteristics, patient education and knowledge in relation to further ER visits over a 12 month period. Methods: Eighty-four patients with asthma and 52 with COPD, who had had an ER visit, were included. They were interviewed by telephone 4 to 6 weeks after the ER visit and followed for a year. Results: Patients with COPD were older, more sedentary, had had more ER visits the previous year, and had more co morbidity than patients with asthma. About 80% of the patients had received information from health professionals or participated in education/rehabilitation, but a minority (< 20%) reported that their knowledge about how to handle the disease was good. Patients with "good knowledge" were younger, were more likely to have asthma diagnose, and had a higher educational background (p < 0.05). Sixty-seven percent of the patients with COPD had repeated ER visits during the following year versus 42% in asthma (p < 0.05) (adjusted HRR: 1.73 (1.03-2.90)). Patients who had had ER visits the year before inclusion had a higher risk of ER visits the following year (adjusted HRR: 3.83 (1.99-7.38)). There were no significant differences regarding patient education and knowledge between the group with and without further ER visits after adjusting for sex, diagnose, age, and educational background. Conclusion: Patients with asthma had a better self reported knowledge of disease management and were less likely to have new exacerbations than patients with COPD. Reported level of knowledge was, however, in it self not a predictor of exacerbations. This indicates that information is not sufficient to reduce the burden of disease. Patient education focused on self-management and behavioral change should be emphasized.

Effect of traffic pollution on respiratory and allergic disease in adults: cross-sectional and longitudinal analyses

Mar Pujades-Rodriguez — 2009-08-24T00:00:00Z

Background: Epidemiological research into the role of traffic pollution on chronic respiratory and allergic disease has focused primarily on children. Studies in adults, in particular those based on objective outcomes such as bronchial hyperresponsiveness, skin sensitisation, and lung function, are limited. Methods: We have used an existing cohort of 2644 adults aged 18–70 living in Nottingham, UK, for whom baseline health and demographic data were collected in 1991 and computed two markers of exposure to traffic: distance between the home and nearest main road and modelled outdoor nitrogen dioxide (NO2) concentration at the home location. Using multiple regression techniques, we analysed cross-sectional associations with bronchial hyperresponsiveness, FEV1, spirometry-defined COPD, skin test positivity, total IgE and questionnaire-reported wheeze, asthma, eczema and hayfever in 2599 subjects, and longitudinal associations with decline in FEV1 in 1329 subjects followed-up nine years later in 2000. Results: There were no significant cross-sectional associations between home proximity to the roadside or NO2 level on any of the outcomes studied (adjusted OR of bronchial hyperresponsiveness in relation to living ≤150 m vs >150 m from a road = 0.92, 95% CI 0.68 to 1.24). Furthermore, neither exposure was associated with a significantly greater decline in FEV1 over time (adjusted mean difference in ΔFEV1 for living ≤150 m vs >150 m of a road = 10.03 ml, 95% CI, -33.98 to 54.04). Conclusion: This study found no evidence to suggest that living in close proximity to traffic is a major determinant of asthma, allergic disease or COPD in adults.

T-cell-based diagnosis of tuberculosis infection in children in Lithuania: a country of high incidence despite a high coverage with bacille Calmette-Guerin vaccination

Edita Hansted — 2009-08-18T00:00:00Z

Background: Lithuania is a country with a high incidence of tuberculosis (TB), despite a high coverage with bacille Calmette-Guerin (BCG) vaccination. Until now the only method used to detect latent TB infection was the tuberculin skin test (TST). However, TST may have a cross reactivity to the BCG vaccine and to environmental mycobacteria. The aim of this study was to conduct assessments of the diagnostic accuracy of the T-cell based test (T SPOT TB) for TB in children who had previously been BCG vaccinated and compare these with the results of the TST. Methods: Between January 2005 and February 2007, children with bacteriologically confirmed TB, children having contacts with a case of infectious pulmonary TB and children without any known risk for TB were tested with both the TST and T SPOT TB. Results: The TST and T SPOT TB tests were positive for all patients in the „culture-confirmed TB“ group. Whereas, in the „high risk for TB“ group, the TST was positive for 60%, but the T SPOT TB test, only for 17.8%. Meanwhile the results for the „low risk for TB“ group were 65.4% and 9.6%, respectively. A correlation between the TST and T SPOT TB was obtained in the "culture-confirmed TB" group where the TST ≥15 mm (r = 0.35, p < 0.001). Conclusion: The T-cell based method is more objective than the TST for identifying latent TB infection in children who had been previously BCG vaccinated. This method could be useful in countries like Lithuania where there is a high incidence of TB despite a high coverage with BCG vaccination. It may also help to avoid unnecessary chemoprophylaxis when TST reactions are false-positive.

A solitary bronchial papilloma with unusual endoscopic presentation: case study and literature review

Fabrice Paganin — 2009-08-18T00:00:00Z

Background: Solitary endobronchial papillomas (SEP) are rare tumors and most of them are described by case report. A misdiagnosis is common with viral related papillomas. A histopathological classification has recently permitted a major advancement in the understanding of the disease.Case PresentationWe report a case of a mixed bronchial papilloma with an unusual endoscopic presentation. The literature was extensively reviewed to ascertain the unusual characteristics of the current case. A 39-year of age male was referred to our institution for the investigation of a slight hemoptysis. Routine examination was normal. A fibroscopy revealed an unusual feature of the right main bronchus. The lesion was a plane, non-bleeding, non-glistering sub-mucosal proliferation. No enhanced coloration was noticed. Biopsies revealed a mixed solitary bronchial papilloma. In situ HPV hybridization was negative. Endoscopic treatment (electrocautery) was effective with no relapse. Conclusion: This lesion contrasts with the data of the literature where papilloma were described as wart-like lesions or cauliflower tumors, with symptoms generally related to bronchial obstruction. We advise chest physicians to be cautious with unusually small swollen lesions of the bronchi that may reveal a solitary bronchial papilloma. Endoscopic imaging can significantly contribute to the difficult diagnosis of SEP by pulmonary physicians and endoscopists.