Serum vitamin D is associated with improved lung function markers but not with prevalence of asthma, emphysema, and chronic bronchitis.

Hypovitaminosis D has been linked to several non-bone diseases. Relation between 25-hydroxyvitamin D [25(OH)D] and lung function and lung diseases has received little attention at the global level. Cross-sectional data from three National Health and Nutrition Examination Surveys, 2007-2008, 2009-2010, and 2011-2012 were used to investigate the relationship between serum 25(OH)D concentrations and lung function makers [forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)] and lung diseases (asthma, emphysema, and chronic bronchitis) with multivariate regression models (n = 11,983; men, 6,010; women, 5,973). Serum 25(OH)D concentrations were directly associated with FVC and FEV1 (P for trend < 0.01). Individuals in the 4th quartile serum 25(OH)D had significantly higher FVC and FEV1 compared to those in the 1st quartile (P < 0.01). When data were stratified based on gender and smoking status, we found similar associations between serum 25(OH)D concentrations and lung function markers. There was no relation between serum 25(OH)D and prevalence of asthma, chronic bronchitis, and emphysema in US adults. Serum 25(OH)D concentration is associated with improved lung function markers but not with the prevalence of asthma, emphysema, and chronic bronchitis. Controlled studies are needed to determine if the vitamin D supplementation improves lung function in adults and in smokers.

[SERUM CONTENTS OF SUBSTANCE P, ENDOTHELIN-1 AND VASOACTIVE INTESTINAL PEPTIDE IN CHILDREN WITH RECURRENT BRONCHITIS AND VERTEBROBASILAR INSUFFICIENCY].

The recurrent bronchitis (RB) course is caused by the bronchi secretory-evacuation mechanisms state, which provide clearance from pathogens. This mechanism can be disrupted by vegetative reflexes and neuropeptides imbalance that develops in children with the syndrome of the vertebrobasilar arterial system (SVBAS). The objective: study of the neurogenic maintenance of the RB pathogenesis in children with SVBAS by studying the serum content of substances affecting of the bronchial mucosa secretory-evacuation function and inflammatory activity (substance P, vasoactive intestinal peptide - VIP and endothelin-1 - ET-1). 90 children aged 7 to 11 years were examined, 3 observation groups were formed: Group 1 - children with RB and SVBAS (n=30); Group 2 - children with SVBAS without RB (n=30); Group 3 - children with RB without SVBAS (n=30). In the Group 1, compared with the 2nd and 3rd, there was an increase in the children number with high serum content of substance P (by 66.7% and 50.0%, respectively, p<0.05) and ET -1 (by 23.3% and 40.0%, respectively, p<0.05), low content of VIP (by 46.7% and 23.4%, respectively, p<0.05). Children with RB and SVBAS have serum level imbalance of the pro-inflammatory substance P, ET-1 and anti-inflammatory VIP as the bronchitis severe course basis.

Colistin Use in Patients with Chronic Kidney Disease: Are We Underdosing Patients?

Colistin is administered as its inactive prodrug colistimethate (CMS). Selection of an individualized CMS dose for each patient is difficult due to its narrow therapeutic window, especially in patients with chronic kidney disease (CKD). Our aim was to analyze CMS use in patients with CKD. Secondary objectives were to assess the safety and efficacy of CMS in this special population. In this prospective observational cohort study of CMS-treated CKD patients, CKD was defined as the presence of a glomerular filtration rate (GFR) < 60 mL/min/m² for more than 3 months. The administered doses of CMS were compared with those recently published in the literature. Worsened CKD at the end of treatment (EOT) was evaluated with the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria. Colistin plasma concentrations (Css) were measured using high-performance liquid chromatography. Fifty-nine patients were included. Thirty-six (61.2%) were male. The median age was 76 (45⁻95) years and baseline GFR was 36.6 ± 13.6. The daily mean CMS dosage used was compared with recently recommended doses (3.36 vs. 6.07; p < 0.001). Mean Css was 0.9 (0.2⁻2.9) mg/L, and Css was <2 mg/L in 50 patients (83.3%). Clinical cure was achieved in 43 (72.9%) patients. Worsened renal function at EOT was present in 20 (33.9%) patients and was reversible in 10 (52.6%). The CMS dosages used in this cohort were almost half those currently recommended. The mean achieved Css were under the recommended target of 2 mg/dL. Despite this, clinical cure rate was high. In this patient cohort, the incidence of nephrotoxicity was similar to those found in other recent studies performed in the general population and was reversible in 52.6%. These results suggest that CMS is safe and effective in patients with CKD and may encourage physicians to adjust dosage regimens to recent recommendations in order to optimize CMS treatments.

Up-regulation of serum periostin and squamous cell carcinoma antigen levels in infants with acute bronchitis due to respiratory syncytial virus.

BACKGROUND: Periostin and squamous cell carcinoma antigen (SCCA) are involved in the pathogenesis of asthma. Acute bronchitis due to respiratory syncytial virus (RSV) infection during infancy exhibits an asthma-like pathogenesis, suggesting that it may be associated with the subsequent development of asthma. However, the mechanism by which RSV infection leads to development of asthma has not yet been fully elucidated. METHODS: Infants younger than 36 months were enrolled and classified into three groups. Group I included patients hospitalized with RSV-induced bronchitis. These patients were further stratified into two sub-groups according to whether the criteria for the modified Asthma Predictive Index (mAPI) had been met: Group I consisted of mAPI (+) and mAPI (-) patients; Group II included patients with food allergy as a positive control group; and Group III included children with no allergy as a negative control group. Serum periostin and SCCA levels were measured in the groups. This study was registered as a clinical trial (UMIN000012339). RESULTS: We enrolled 14 subjects in Group I mAPI (+), 22 in Group I mAPI (-), 18 in Group II, and 18 in Group III. In Group I, the serum periostin and SCCA levels were significantly higher during the acute phase compared with the recovery phase. However, no significant differences were found between Group I mAPI (+) and mAPI (-). CONCLUSIONS: The serum periostin and SCCA levels increased during acute RSV bronchitis. Both periostin and SCCA may play a role in the pathogenesis of acute bronchitis due to RSV.

Observation of the effects of the Suhuang Zhike capsule on acute bronchitis.

Acute bronchitis is one of the most common diseases in the world. The Suhuang Zhike capsule is a part of Traditional Chinese Medicine (TCM) that was approved to treat acute bronchitis. In order to study the clinical effects of the Suhuang Zhike capsule on acute bronchitis subjects, the clinical data of 96 patients from the Department of Lung Disease of Zhengzhou Traditional Chinese Hospital from June 2014 to June 2014 were retrospectively analyzed. The patients were randomly divided into a control group and a Suhuang Zhike capsule treatment group, each with 48 cases. The therapeutic effects of the treatments were evaluated on the tenth day. The results showed that the total effective rate of the observation group was 95.83%, which was significantly higher when compared with the control group, which was 72.91% (P less than 0.005). The clinical signs (e.g. coughing, itchy throat, dry cough without phlegm, little sputum) of the two groups obviously decreased, and the difference was statistically significant when compared with the pretreatment scores (P less than 0.005). The decreased rate of the observation group was significantly larger when compared with the control group (P less than 0.005). The time it took for the clinical symptoms of the observation group to resolve was significantly shorter when compared with the control group (P less than 0.005). After treatment, the serum levels of c-reactive protein (CRP), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α) of the two groups obviously decreased. There was a significant difference in these serum levels when compared with pre-treatment levels (P less than 0.005). The decreased rate of the observation group was obviously larger when compared with the control group (P less than 0.005). In the observation group, there were 3 cases with adverse reactions (nausea in 2 cases and mild vomiting in 1 case) during the observation period, with an adverse reaction rate of 6.25% In the control group, 10 cases developed adverse reactions (nausea in 2 cases, mild diarrhea in 3 cases, and mild vomiting in 5 cases), with an adverse reaction rate of 20.83% (P less than 0.005, vs the observation group). In this study, we showed that the Suhuang Zhike capsule provides positive therapeutic effects in the treatment of acute bronchitis by promoting the alleviation of the clinical symptoms in a short time and reducing the inflammation in the respiratory tract.

Increased Systemic Cytokine/Chemokine Expression in Asthmatic and Non-asthmatic Patients with Bacterial, Viral or Mixed Lung Infection.

This study was aimed to determine the profiles of serum cytokines (IL-1ß, TNF-α, IL-4, IL-5) and chemokines (MCP-1: monocyte chemoattract protein-1 and RANTES: regulated on activation normal T cell expressed and secreted) in individuals with an asthmatic versus a non-asthmatic background with bacterial, viral or mixed acute respiratory infection. Asthmatic (n = 14) and non-asthmatic (n = 29) patients with acute viral, bacterial or mixed (bacterial and viruses) respiratory infection were studied. Patients were also analysed as individuals with pneumonia or bronchitis. Healthy individuals with similar age and sex (n = 10) were used as controls. Cytokine/chemokine content in serum was determined by ELISA. Increased cytokine/chemokine concentration in asthmatic and non-asthmatic patients was observed. However, higher concentrations of chemokines (MCP-1 and RANTES) in asthmatic patients infected by viruses, bacteria or bacteria and viruses (mixed) than in non-asthmatic patients were observed. In general, viral and mixed infections were better cytokine/chemokine inducers than bacterial infection. Cytokine/chemokine expression was similarly increased in both asthmatic and non-asthmatic patients with pneumonia or bronchitis, except that RANTES remained at normal levels in bronchitis. Circulating cytokine profiles induced by acute viral, bacterial or mixed lung infection were not related to asthmatic background, except for chemokines that were increased in asthmatic status.

Biomarkers of extracellular matrix turnover are associated with emphysema and eosinophilic-bronchitis in COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and loss of lung tissue mainly consisting of extracellular matrix (ECM). Three of the main ECM components are type I collagen, the main constituent in the interstitial matrix, type VI collagen, and elastin, the signature protein of the lungs. During pathological remodeling driven by inflammatory cells and proteases, fragments of these proteins are released into the bloodstream, where they may serve as biomarkers for disease phenotypes. The aim of this study was to investigate the lung ECM remodeling in healthy controls and COPD patients in the COPDGene study. METHODS: The COPDGene study recruited 10,300 COPD patients in 21 centers. A subset of 89 patients from one site (National Jewish Health), including 52 COPD patients, 12 never-smoker controls and 25 smokers without COPD controls, were studied for serum ECM biomarkers reflecting inflammation-driven type I and VI collagen breakdown (C1M and C6M, respectively), type VI collagen formation (Pro-C6), as well as elastin breakdown mediated by neutrophil elastase (EL-NE). Correlation of biomarkers with lung function, the SF-36 quality of life questionnaire, and other clinical characteristics was also performed. RESULTS: The circulating concentrations of biomarkers C6M, Pro-C6, and EL-NE were significantly elevated in COPD patients compared to never-smoking control patients (all p < 0.05). EL-NE was significantly elevated in emphysema patients compared to smoking controls (p < 0.05) and never-smoking controls (p < 0.005), by more than 250%. C1M was inversely associated with forced expiratory volume in 1 s (FEV1) (r = -0.344, p = 0.001), as was EL-NE (r = -0.302, p = 0.004) and Pro-C6 (r = -0.259, p = 0.015). In the patients with COPD, Pro-C6 was correlated with percent predicted Forced Vital Capacity (FVC) (r = 0.281, p = 0.046) and quality of life using SF-36. C6M and Pro-C6, were positively correlated with blood eosinophil numbers in COPD patients (r = 0.382, p = 0.006 and r = 0.351, p = 0.012, respectively). CONCLUSIONS: These data suggest that type VI collagen turnover and elastin degradation by neutrophil elastase are associated with COPD-induced inflammation (eosinophil-bronchitis) and emphysema. Serological assessment of type VI collagen and elastin turnover may assist in identification of phenotypes likely to be associated with progression and amenable to precision medicine for clinical trials.

Serum levels of the soluble haemoglobin scavenger receptor CD163 in MPO-ANCA-associated renal vasculitis.

OBJECTIVES: The contribution of infections to the mortality of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is important, and early and careful infection control is necessary. We investigated the usefulness of the serum-soluble haemoglobin scavenger receptor CD163 for detecting the presence of infectious complications regardless of disease activity. METHOD: Soluble CD163 in serum obtained from 45 Japanese patients with myeloperoxidase (MPO)-AAV was measured by an enzyme-linked immunosorbent assay (ELISA). We evaluated 36 samples from active-vasculitis patients, 36 samples from inactive-vasculitis patients without infection, and 19 samples from inactive-vasculitis patients with infectious complications. Serum-soluble CD163 was also measured in 15 infectious patients without vasculitis and in 30 normal controls. RESULTS: The mean serum-soluble CD163 level was higher in the patients with infectious complications than in the active-vasculitis patients, inactive-vasculitis patients, and normal controls. There were significant positive correlations between serum-soluble CD163 levels and white blood cell (WBC) count, serum C-reactive protein (CRP) levels, and serum albumin levels, but only serum CRP levels were correlated with serum-soluble CD163 levels in a multiple regression analysis. On the receiver-operating characteristic (ROC) curve, serum-soluble CD163 levels had 80.6% sensitivity and 86.7% specificity for differentiating patients with infection from those without infection. Among the active-vasculitis patients, the mean serum-soluble CD163 level of the patients with alveolar haemorrhage was significantly lower than that of the patients with interstitial lung diseases and that of the patients without pulmonary lesions. CONCLUSIONS: The serum-soluble CD163 level may be a useful marker for the detection of infectious complications in MPO-AAV patients.

Evaluation of Blood Alcohol Concentrations after Oral Administration of a Fixed Combination of Thyme Herb and Primrose Root Fluid Extract to Children with Acute Bronchitis.

BACKGROUND: The application of alcohol-containing medicinal products to children has been a subject of discussion for many years. A safety threshold of 0.125‰ blood alcohol concentration following the administration of a single dose has been recommended by the European Medicines Agency.The aim of this clinical study was to prove the safety of administering a fixed combination of thyme herb and primrose root fluid extract (Bronchicum(®) Elixir) containing 4.9% ethanol. METHODS: The herbal drug was administered for a period of 7-9 days to 16 children (ages 1-12 years) suffering from acute bronchitis for ≤ 48 h. After 3-5 days, a blood sample was taken 45 min (children ≥ 5 years: also 0 and 90 min) after application of the drug. The efficacy was assessed using the Bronchitis Severity Score. Global efficacy and tolerability were rated by the investigator and patients. RESULTS: All measured blood ethanol concentrations were below the threshold (mean value after 45 min: 0.0029 ± 0.0057‰ and after 90 min: 0.0051 ± 0.0078‰). The Bronchitis Severity Score decreased from 6.6 ± 1.0 to 0.9 ± 1.6 points. Global efficacy was assessed as "very good" and "good" in 60% (investigator) and 80% (patients) of cases. Global tolerability was rated as "very good" and "good" in more than 90% of cases. CONCLUSION: In conclusion, oral administration of the drug containing 4.9% ethanol to children (age 1-12 years) demonstrated a favourable risk/benefit ratio of the drug.

[DYNAMICS OF CYTOKINES IN INFANTS WITH ACUTE OBSTRUCTIVE BRONCHITIS AND THYMOMEGALIA].

The article contains the information about pro- and anti-inflammatory cytokines in infants with acute obstructive bronchitis and thymus hypertrophy. The content of IL-6 and IL-10 has been de- termined in 101 children in acute period of disease and during early convalescence. It was found the increasing of production of proinflammatory IL-6 and a low level of anti-inflammatory IL-10 in the first days of illness in all children with thymomegalia. During convalescence in patients with acute obstructive bronchitis and thymomegalia IL-6 level was decreasing, and the level of IL-10 was in- creasing, but it did not amount to the level of healthy children.

Cellular and Soluble Inflammatory Markers in Induced Sputum of Composting Plant Workers.

Inflammatory processes, including respiratory symptoms, can be induced among workers in composting plants exposed to bioaerosols containing microorganisms and their compounds. We evaluated inflammatory processes in the lower respiratory tract via cellular and soluble mediator profiles in induced sputum (IS). IS samples of 140 current (35% smokers) and 49 former compost workers (29% smokers) as well as 29 white-collar workers (17% smokers) were collected and analyzed for the cell count and composition, and for soluble biomarkers. Significant differences between current and former compost workers and white-collar workers were detected for total cell count (p=0.0004), neutrophils (p=0.0045), sCD14 (p=0.008), and 8-isoprostane (p<0.0001). IS of non-smoking former compost workers showed lower concentrations of IL-8, total protein, immunoreactive MMP-9 and sCD14, compared with non-smoking current compost workers. 10.1% of the study population was suffering from chronic bronchitis with significant differences (p=0.018) between former compost workers (24.5%), current workers (5%), and white-collar workers (10.3%). Significantly lower IL-8 (p=0.0002), neutrophils (p=0.001), and MMP-9 (p=0.0023) values were measured in healthy subjects compared with subjects with chronic bronchitis. In conclusion, changes in lower airways were detected by analysis of biomarkers in IS of current exposed and, to a lesser extent, in IS of former compost workers. These effects are especially pronounced in subjects with chronic bronchitis.

[SOME CLINICAL AND CYTOKINE FEATURES OF THE CLINICAL COURSE OF RECURRENT RESPIRATORY SYSTEM DISEASES IN CHILDREN WITH THE TOXOCARIASIS INVASION].

The aim of the present study was to analyze clinical and cytokine features of recurrent respiratory system diseases in children with toxocariasis. 50 children aged 1 to 17 years (mean age - 10±5 years) with recurrent current of respiratory system disorders were studied. During the survey such clinical manifestations of the respiratory system disorders as obstructive bronchitis (50%), bronchial asthma (30%), pneumonia (10%) and laryngotracheitis (10%) have been revealed. Statistical analysis of the results was performed using the software package STATISTICA 6.1 (SNANSOFT). We have shown that the disorders of respiratory system in case of toxocariasis invasion often occur with severe intoxication and bronchial obstruction syndromes, temperature reaction, respiratory insufficiency and hepatomegaly. A prolonged course of the disease has been noted. "Inflammatory" indicators of general blood analysis, such as leukocytosis and increased of ESR have been recorded in patients with respiratory system disorders in children with T.canis infection significantly more often, significant "allergic" laboratory changes were in the form of eosinophilia. High average levels of pro-inflammatory IL-6, as well as low levels of IL 5 have been determined in children suffering from the respiratory system disorders and with toxocariasis invasion in the anamnesis. The obtained findings require further study.

Is C-reactive protein testing useful to predict outcome in patients with acute bronchitis?

BACKGROUND: A recent clinical trial could not find differences between anti-inflammatory drugs, antibiotics and placebo in shortening the duration of symptoms in acute bronchitis. OBJECTIVES: To investigate if C-reactive protein (CRP) concentrations at presentation are predictive of symptom resolution in these patients. METHODS: We performed a secondary analysis of the data from a placebo-controlled, randomized clinical trial carried out in primary care. Patients from 18 to 70 years of age presenting a respiratory tract infection of <1 week of evolution, with cough as the predominant symptom and the presence of discoloured expectoration, were enrolled in the study. On the baseline visit, CRP was determined in capillary blood and a five-item symptom diary was given. Patients were followed up to 30 days. The main outcome measure was the number of days with persistent cough. RESULTS: A total of 312 subjects fulfilled all the criteria for the efficacy analysis and had undergone the CRP test; of these, 56.4% presented a CRP value <8 mg/l and 76% presented <20 mg/l. There were no significant differences in the median duration of cough: 10 days among patients with CRP concentrations <8 mg/l [95% confidence interval (CI): 8-11 days], 11 days among those with concentrations ranging from 8 to 19 mg/l (95% CI: 8-16) and 11 days in those with CRP >20 mg/l (95% CI: 9-12) (P = 0.337). CONCLUSION: Among patients with uncomplicated acute bronchitis and discoloured sputum, the CRP concentrations at presentation are not helpful for predicting symptom resolution.

The utility of biomarkers in differentiating bacterial from non-bacterial lower respiratory tract infection in hospitalized children: difference of the diagnostic performance between acute pneumonia and bronchitis.

The aim of this study is to investigate the utility of several biomarkers in differentiating bacterial community-acquired lower respiratory tract infection (CA-LRTI) from non-bacterial CA-LRTI in children and the difference of their diagnostic performance between pneumonia and bronchitis. A retrospective cohort study composed of 108 pediatric patients hospitalized for CA-LRTI was performed during 2010-2013. Based on the findings of chest X-ray and sputum samples, patients were divided into 4 categories, group of bacterial pneumonia or bronchitis, and non-bacterial (viral or etiology-unknown) pneumonia or bronchitis. Peripheral white blood cell and neutrophil counts, and serum C-reactive protein (CRP) and procalcitonin (PCT) levels were compared among the 4 groups. Finally, 54 patients were the subject of this study. In the patients with pneumonia, serum CRP and PCT levels were significantly elevated in the group of bacterial pneumonia (CRP: p = 0.02, PCT: p = 0.0008). The area under the receiver operating characteristic curve for PCT for distinguishing between bacterial and non-bacterial pneumonia was the largest, and sensitivity, specificity, positive predictive value and negative predictive value of PCT were best among 4 markers. On the other hand, in the patients with bronchitis, neutrophil count was significantly decreased in non-bacterial bronchitis whereas no significant differences of WBC count, CRP level or PCT level were seen. In conclusion, PCT was the most useful marker to differentiate bacterial pneumonia whereas neutrophil count contributed most to the discrimination of bacterial bronchitis. The diagnostic performance of biomarkers may be different between pneumonia and bronchitis.

Inhaled corticosteroids and systemic inflammatory response in community-acquired pneumonia: a prospective clinical study.

BACKGROUND AND OBJECTIVE: The previous use of inhaled corticosteroids (ICS) may reduce the inflammatory response and mortality in patients with community-acquired pneumonia (CAP). METHODS: We measured serum levels of several inflammatory biomarkers, as well as mortality at various time-points, in 663 consecutive patients hospitalized for CAP; 128 (19%) were receiving chronic outpatient treatment with ICS. Patients on previous oral corticosteroids were excluded from the analysis. RESULTS: On admission, patients treated with ICS were older; had been diagnosed with chronic obstructive pulmonary disease (COPD), asthma and pneumonia in the previous year more often; and had higher CAP severity risk classes and lower tumour necrosis factor (TNF)-alpha (P < 0.001) and interleukin (IL)-6 (P = 0.015) serum levels. After adjusting for potential confounders, this association persisted for TNF-alpha (P < 0.001), but not for IL-6. Mortality at 30 and 90 days tended to be lower in patients treated with ICS (P = 0.062 and 0.050, respectively), but mortality was similar after 1 year in both groups (16, 13% vs 81, 15% for patients treated and not treated with ICS, respectively). Hospital readmission rate after 1 year was higher in patients treated with ICS (49, 38% vs 109, 20%, P < 0.001). The association of ICS treatment with a previous diagnosis of pneumonia, lower levels of TNF-alpha and IL-6 on admission and higher readmission rates during follow up persisted in the subpopulation of 210 patients with COPD. CONCLUSIONS: Previous use of ICS in patients hospitalized for CAP is associated with a reduced systemic inflammatory response without any impact on long-term mortality.