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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., (Copyright © 2018 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

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., (Copyright © 2014. Published by Elsevier Ltd.)

A 56-year-old woman was referred to our hospital because of dyspnea, wheezing, and a productive cough. Eight years before presentation, bronchial asthma was diagnosed and the patient received inhaled corticosteroids plus antiasthmatic agents (a long-acting inhaled beta2-agonist, leukotriene modifiers, and theophylline). Chest radiography showed small diffuse nodular shadows, and a computed tomographic scan showed thickening of the bronchi and bronchioles, with diffuse centrilobular nodules in both lung fields. A blood test and microscopic examination of the bronchoalveolar fluid revealed marked eosinophilia. Transbronchial lung biopsy and transbronchial biopsy showed eosinophilic bronchitis and bronchiolitis. After treatment with oral prednisolone (40 mg daily) and inhaled corticosteroids, the symptoms, blood eosinophilia, and radiographic findings improved. Recently, several similar cases of eosinophilic bronchiolitis have been reported. Studies of further cases and elucidation of the pathophysiology of eosinophilic bronchiolitis are necessary to establish a concept for this disease and to determine whether it should be classified as a subtype of bronchial asthma or as a distinct entity.

Aim: The role of high mobility group box protein 1 (HMGB1) in non-small cell lung cancer (NSCLC) is unknown. We investigated the contributions of HMGB1 in NSCLC, and analyze the correlation between HMGB1 and clinicopathologic outcomes., Patients and Methods: A total of 145 patients with diagnosed NSCLC, and 77 patients with diagnosed chronic obstructive pulmonary disease (COPD) (51 chronic bronchitis and 26 obstructive pulmonary emphysema), and 49 healthy volunteers were enrolled from January 2005 through July 2008. HMGB1 levels were analyzed by Western blot analysis., Results: The mean value of serum HMGB1 levels in 145 patients with lung cancer was 76.1+/-37.0ng/ml and was significantly higher than those in 77 COPD patients (39.8+/-10.8ng/ml), and 49 healthy control (7.7+/-6.1ng/ml, p<0.0001, respectively); The serum HMGB1 levels were 30.2+/-5.9ng/ml, 60.9+/-22.5ng/ml, 99.0+/-23.1ng/ml and 133.4+/-18.9ng/ml in patients with NSCLC of TNM stage I, II, III, and IV. There were significant differences among four groups (p<0.0001). Moreover, the significant positive correlation between the levels of serum HMGB1 and the size of tumor (r=0.799, p<0.001); The serum HMGB1 levels were 57.2+/-28.8ng/ml in patients with NSCLC before operation, and 26.5+/-14.7ng/ml one month after operation (p<0.0001)., Conclusions: Our study suggests that HMGB1 may be a useful clinical marker for evaluating the NSCLC progression and is of potential prognostic value.

Background: Lower respiratory tract infections are often treated with antibiotics without evidence of clinically relevant bacterial disease. Serum calcitonin precursor concentrations, including procalcitonin, are raised in bacterial infections. We aimed to assess a procalcitonin-based therapeutic strategy to reduce antibiotic use in lower respiratory tract infections with a new rapid and sensitive assay., Methods: 243 patients admitted with suspected lower respiratory tract infections were randomly assigned standard care (standard group; n=119) or procalcitonin-guided treatment (procalcitonin group; n=124). On the basis of serum procalcitonin concentrations, use of antibiotics was more or less discouraged (<0.1 microg/L or <0.25 microg/L) or encouraged (> or =0.5 microg/L or > or =0.25 microg/L), respectively. Re-evaluation was possible after 6-24 h in both groups. Primary endpoint was use of antibiotics and analysis was by intention to treat., Findings: Final diagnoses were pneumonia (n=87; 36%), acute exacerbation of chronic obstructive pulmonary disease (60; 25%), acute bronchitis (59; 24%), asthma (13; 5%), and other respiratory affections (24; 10%). Serological evidence of viral infection was recorded in 141 of 175 tested patients (81%). Bacterial cultures were positive from sputum in 51 (21%) and from blood in 16 (7%). In the procalcitonin group, the adjusted relative risk of antibiotic exposure was 0.49 (95% CI 0.44-0.55; p<0.0001) compared with the standard group. Antibiotic use was significantly reduced in all diagnostic subgroups. Clinical and laboratory outcome was similar in both groups and favourable in 235 (97%)., Interpretation: Procalcitonin guidance substantially reduced antibiotic use in lower respiratory tract infections. Withholding antimicrobial treatment did not compromise outcome. In view of the current overuse of antimicrobial therapy in often self-limiting acute respiratory tract infections, treatment based on procalcitonin measurement could have important clinical and financial implications.

Study Objectives: In a 2-year longitudinal study of boilermaker construction workers, we found a significant association between working at oil-fired, coal-fired, and gas-fired industries during the past year and reduced lung function. In the present study, we investigated whether chronic bronchitis, asthma, or baseline methacholine airway responsiveness can explain the heterogeneity in lung function response to boilermaker work., Design: This study is part of an ongoing prospective cohort study of boilermakers. Exposure was assessed with a work history questionnaire. Spirometry was performed annually to assess lung function. A generalized estimating equation approach was used to account for the repeated-measures design., Setting: Boilermaker union members., Participants: One hundred eighteen boilermakers participated in the study., Interventions: None., Measurements and Results: Self-reported history of chronic bronchitis and asthma were associated with a larger FEV1 reduction in response to workplace exposure at coal-fired and gas-fired industries. Although we found a high prevalence (39%) of airway hyperresponsiveness (provocative concentration of methacholine causing a 20% fall in FEV1 of < 8 mg/mL) among boilermakers, we did not find a consistent pattern of effect modification by airway responsiveness., Conclusions: Although chronic bronchitis and asthma were associated with a greater loss in lung function in response to hours worked as a boilermaker, and therefore they acted as effect modifiers of the exposure-lung function relationship, airway hyperresponsiveness did not. However, the high prevalence of airway hyperresponsiveness found in the cohort may be a primary consequence of long-term workplace exposure among boilermakers.

One of the issues concerning harmonization in the development of pharmaceutical products, especially antimicrobials, is discrepancy in the indications to be studied clinically. In particular, it has been very much questioned whether the underlying disease in Western patients diagnosed with acute exacerbation of chronic bronchitis (AECB) is identical with chronic bronchitis in Japan. We assessed chest X-ray films from 105 AECB patients enrolled in a clinical study of SB265805 (a fluoroquinolone antibacterial agent under development) conducted in Europe, and then compared their clinical signs/symptoms and laboratory data with Japanese historical data. Five of the 105 patients did not meet the criteria of AECB; i.e., 2 of them were diagnosed with pneumonia, 1 with bronchiectasis, 1 with pneumoconiosis, and 1 with bronchiectasis plus pulmonary emphysema. In the remaining 100 patients, chest X-ray findings and laboratory test results were consistent with the concept of chronic bronchitis, although 23 of them had other cardiac or pulmonary diseases as well. There were significant imbalances in distribution between Western patients and Japanese historical data in terms of age, cough, WBC counts, and C-reactive protein (CRP) levels. Compared with Japanese historical data, Western patients were younger and had a more severe cough, although increases in WBC and CRP were less remarkable. For other variables, i.e., sex, fever, and volume of sputum, no significant difference was detected in distribution. Overall, there was no significant difference between the two groups in regard to disease severity, as assessed by fever, WBC, and CRP.

Positive association has been suggested between a variety of infections and coronary heart disease. Disturbances in blood coagulation system may form a link between infections and coronary heart disease. The aim of this study was to analyze whether chronic bronchitis, defined by the occurrence of symptoms, is associated with selected haemostatic factors in a cross-sectional population study of 2379 Finnish men and women aged between 45 and 64 years. Plasma fibrinogen level was significantly higher, 3.70 versus 3.35 g/l (P < 0.001) in men and 3.64 versus 3.44 g/l (P < 0.001) in women, among subjects with symptoms of chronic bronchitis than among those without symptoms. The association was independent of age, smoking, body mass index, physical exercise, and alcohol consumption. Also plasminogen was higher among men with symptoms than among those without but the difference disappeared after adjustment for age and smoking. Factor VII coagulant activity and factor VII antigen level did not differ between subjects with and without symptoms. Thus, fibrinogen may be associated with a possible mechanism to link chronic bronchitis to coronary heart disease risk, even though the causality of the association cannot be verified in a cross-sectional study.

von Willebrand factor (vWF) is a large glycoprotein secreted predominantly by endothelial cells in both the systemic and pulmonary circulations and has a central role in the formation of the platelet plug. It has been put forward as a possible marker of endothelial cell injury, but is not ideal in that it is not specific for either the pulmonary or systemic circulation and may be released as part of the acute phase response from otherwise healthy endothelial cells. We undertook two studies (i) to assess within-subject to assess within-subject variation in plasma von Willebrand factor antigen (vWF:Ag) levels over time and to assess between-subject variation in a healthy patient population, and (ii) as part of a descriptive study of acute bronchitis, to assess whether plasma vWF:Ag levels altered in such a common and minor insult. A random sample of patients aged 45-74 years were taken from a local general practice. vWF:Ag levels were measured on three occasions, and spirometry was performed. The descriptive study was undertaken on patients in the general practice diagnosed with acute bronchitis without pre-existing pulmonary disease. Plasma vWF:Ag was measured on presentation and 14 and 42 days later. In 219 randomly selected patients the mean plasma vWF:Ag was similar at all three visits, the within-subject standard deviation being 0.09 U ml(-1) and 1.12 U ml(-1) respectively). There was no correlation between plasma vWF:Ag and C-reactive protein on presentation. We conclude that there is relatively little variation in an individual's plasma vWF:Ag level but that levels increase significantly with age. The observed elevation occurring with acute bronchitis is a true phenomenon; the absence of an associated acute phase response suggests that endothelial cell injury is the mechanism for the rise. These observations are important in the context of vWF as a marker of endothelial cell damage, as a common and supposedly minor insult such as acute bronchitis may markedly raise plasma levels.

Patients with COPD who fulfill the diagnostic criteria of chronic bronchitis have been shown to exhibit lower serum levels of complement components C3 and C4 than healthy subjects, and this may indicate sustained complement activation as a result of recurrent respiratory tract infections. Since activation of complement leads to influx of inflammatory cells into the lung parenchyma with subsequent release of elastases and oxidants that cause damage to elastic lung tissue, we postulated that there might be a quantitative relationship between complement consumption and degree of elastic tissue destruction. In this study, we tried to investigate possible correlations between serum levels of C3 and C4 and degree of emphysema among patients with COPD of the bronchitic type. We studied 20 patients with chronic bronchitis aged 68+/-1 years (mean+/-SEM) without significant fluctuations of serum C3 and C4 levels over a 3-month period by performing detailed lung function tests, recording of emphysema score in chest radiogram, and the incidence of infective exacerbations during the past 3 years. Measured C3 and C4 serum levels were 124+/-9 and 28.5+/-2 mg/dL, respectively, lower than the respective levels in control subjects (141+/-3 and 39+/-2 mg/dL, respectively). Significant correlations were observed between levels of C4 and (1) incidence of respiratory tract infections during the past 3 years (r=-0.747, p<0.001), (2) radiologic emphysema score (r=-0.936, p<0.001), and (3) various functional indexes, such as midexpiratory flow rate, percent of predicted (r=0.629, p<0.01), forced expiratory flow rate at 50% of vital capacity, percent of predicted (r=0.606, p<0.01), residual volume/total lung capacity ratio (r=-0.651, p<0.01), and the exponential constant of static pressure-volume curve (r=-0.606, p<0.01). These results suggest that patients with chronic bronchitis with the lowest levels of C4 are those experiencing more frequent respiratory infections, tend to have more signs indicative of emphysema in their chest radiograph, have a more prominent small airways dysfunction and gas trapping, and present a greater defect in lung elastic recoil.

Study Objective: The monitoring of serum concentrations of Cyfra 21-1, tumor polypeptide antigen (TPA), and tissue polypeptide specific antigen (TPS) has been demonstrated to be useful in the clinical treatment of patients with lung cancer. This study was planned to evaluate the clinical usefulness of the assay of these tumor markers on bronchial washing (BW) fluid and to compare it with serum assay in patients with neoplastic and nonneoplastic disease., Study Design: Serum and BW fluid levels of Cyfra 21-1, TPA, and TPS were measured in 40 subjects (10 control subjects, 11 with chronic bronchitis, 10 with squamous cell lung cancer, and 9 with nonsquamous cell lung cancer) undergoing diagnostic bronchoscopy. BW was performed using 25 mL of pyrogen-free saline solution instilled through the working channel of the bronchoscope, and successively aspirated. The quantity of the fluid recovered was measured and used for the assay of albumin, Cyfra 21-1, TPA, and TPS., Results: Mean BW concentrations of Cyfra 21-1, TPA, and TPS concentrations were significantly higher than serum concentrations (p < 0.01). Serum Cyfra 21-1, TPA, and TPS concentrations were significantly lower in controls and in those with chronic bronchitis than in patients with epidermoid and nonepidermoid carcinoma (p < 0.01). No difference in serum concentrations of the three markers was observed between controls and patients with chronic bronchitis. On the contrary, BW Cyfra 21-1 and TPA concentrations were significantly higher in those with chronic bronchitis and in cancer patients than in controls (p < 0.01), whereas they did not differ between patients with chronic bronchitis and cancer patients. No significant difference in BW TPS concentration was observed among the four groups. Sensitivity and specificity of the BW markers in diagnosing lung cancer were as follows: 68.4% and 61.9% for Cyfra 21-1; 68.4% and 66.6% for TPA; and 57.9% and 66.6% for TPS., Conclusions: BW fluid concentrations of Cyfra 21-1 and TPA are increased in patients with chronic bronchitis and in patients with lung cancer. Being unable to distinguish malignant from nonmalignant inflammatory conditions, the measurement of airway concentrations of such markers has a too-low specificity to be considered useful in diagnosing malignant abnormalities of the lung.

Retractions of the lower ribcage (chest wall distortion [CWD]) during inspiration are frequently observed with moderate to severe respiratory disease in the infant. Laryngotracheobronchitis (LTB) results in a reversible partial airway obstruction with severe CWD. We wished to measure the motion of the chest wall during distortion to determine the changes in minute ventilation (VE) and to evaluate this clinical sign as a means of assessing disease severity. The respiratory inductance plethysmograph was used to determine the distortion of the lower chest wall, and distortion was correlated with VE, measured at the mouth, in six infants with severe LTB and ventilatory failure. As the conditions of these infants improved, the CWD decreased with decreasing transcutaneous carbon dioxide tension (tcPCO2), VE increased from 0.27 +/- 0.12 L.min-1 x kg-1 at a tcPCO2 of 64 mm Hg to 0.64 +/- 0.06 L.min-1 x kg-1 when the tcPCO2 had fallen to 28 mm Hg. Over the same change in tcPCO2, the tidal volume (VT) increased from 4.8 +/- 0.5 ml.kg-1 to 15.7 +/- 1.4 ml.kg-1. In the most severe disease state, the excursion of the chest wall (as an inductance) was -14 +/- 3 mV in severe obstruction, but increased to 75 mV +/- 4 mV with resolution of the illness. The timing and vector of movement of the abdomen and chest wall were expressed as a Lissajous figure, which is measured as a phase angle. The severity of the disease process, as determined by tcPCO2 was directly related to the phase relationship, and thus reflected both VE and VT. The severity of the CWD may be assessed rapidly by the use of Lissajous figures.

The relationship of peripheral blood leukocyte count to respiratory symptoms was explored in data from the Second Annual National Health and Nutrition Survey (NHANES II). The study sample consisted of 9237 white and nonwhite US adults between the ages of 30 and 74 years. Three respiratory symptom outcomes were utilized: physician-diagnosed chronic cough and chronic bronchitis and self-reported frequent wheeze apart from colds or flu in the past 12 months. Peripheral blood leukocyte counts were performed using a Coulter counter, model FN. Logistic regression analysis was performed for each of the three respiratory symptom outcomes controlling for age, race, gender, and cigarette-years of smoke exposure. The peripheral blood leukocyte count was a significant predictor for each symptom. For a standard deviation increase in the log leukocyte count, the relative odds of wheezing was 1.93 (95% confidence level [CI], 1.47 to 2.52); for chronic cough, 2.29 (95% CI, 1.74 to 3.00); and for bronchitis, 2.44 (95% CI, 1.77 to 3.35). Analyses restricted to never smokers gave similar results. These data suggest that peripheral blood leukocyte count correlates with respiratory symptoms and are consistent with the hypothesis that the leukocyte count is a serum marker of inflammation.

In acute and subacute disease the active thyroid hormones, triiodothyronine (T3) and tetraiodothyroacetic acid (tetrac), are decreased while serum-thyroxine (T4) levels tend to be slightly reduced. Conversely, the inactive metabolite, reverse triiodothyronine (reverse T3), is increased indicating a diversion of T4 metabolism from an activating to an inactivating pathway. With convalescence the serum levels of T3, tetrac, and T4 recover while reverse T3 decreases to normal. These changes occur without significant alterations in serum levels of thyroid-stimulating hormone, indicating maintenance of euthyroidism throughout disease.

Routine results, pH, partial pressure of carbon dioxide (pCO2) and of oxygen (pO2), and standard hydrogen carbonate ion concentration (SBC) in identical specimens of arterial blood from patients deviate substantially. The results from seven laboratories (each laboratory examining the same 12 patients and the same five types of quality control materials) and evaluation in terms of accuracy and precision suggest the variations between days (delta 2) and single measurements (sigma 2) to be the main factors for these deviations. A reduction of these variations must have the highest priority in quality control programmes, since the variations mask possible true level deviations between laboratories. The five control materials (Qualicheck, Quantra whole blood level I-II-III and hemolyzed donor blood) are not fully optimal as substitutes for patient blood in such quality control programmes.

The authors studied 79 patients with chronic obstructive lung disease. (COLD) (FEV1/VC less than 70%). Patients with chronic asthma were excluded from the series. These patients with COLD were divided up into 2 groups, depending on radiological and clinical criteria: (1) Type A, primary emphysema, 24 patients; (2) Type B, chronic bronchitis, 49 patients. 6 patients of type X (intermediate type) were excluded. Their respiratory function tests were studied together with clinical and radiological findings and blood gases. Furthermore, were studied in each patient, the antitrypsic activity and the serum concentrations of alpha-1-antitrypsin and phenotype Pi. Group A were, on average, more obstructive than group B. The ratio FEV1/VC was 31% +/- 7% in group A, against 46% +/- 13% in group B. The serum antitrypsin activity and the serum concentration in alpha-1-AT were on average close to normal in both groups. However, group A was divided up into two populations: a small population with a low concentration of alpha-1-AT, and a large population with normal alpha-1-AT. A study of the incidence of various phenotypes in groups A and B showed a significantly higher frequency of phenotype ZZ in group A (12.5%) than in group B (10%). All ZZ subjects were of clinical type A. There was no significant difference in the incidence of other phenotypes encountered. Serum alpha-1-antitrypsin concentration was very low in 3 ZZ patients. One case with phenotype SZ and one MM showed intermediate levels. The authors emphasize the low percentage of cases of pulmonary emphysema which may be explained by an alpha-1-antitrypsin deficiency. Nevertheless, this preliminary report should be completed by a study of a larger sample of patients with COLD with control of the phenotype.

The effect of passage through the lung on alpha1-antitrypsin was studied in sixteen patients with chronic obstructive airways disease. The average mixed venous value of alpha1-antitrypsin (106.2% standard serum value) was not different from the the mean arterial value (105.6%). Where individual differences were found there was a similar difference in serum albumin. However, there was a small but significant rise (p less than 0.005) in serum alpha1-antitrypsin "complex" as blood traversed the lung (mixed value = 6.3%; mixed arterial value = 6.8%). The reason is not yet clear.

Hypoxic pulmonary vasoconstriction is considered as one of the factors leading to pulmonary hypertension in patients with chronic bronchitis, but the magnitude and the variability of the pulmonary vascular response to hypoxia in these patients have not been well established. We investigated the pulmonary hemodynamic changes induced by breathing two hypoxic mixtures (FIO2 = 0.15 and 0.13) in 26 patients with chronic bronchitis with airway obstruction (FEV1/VC = 49 +/- 14 percent). Results show that there is a wide variability of the pulmonary vascular response to acute hypoxia in chronic bronchitis patients, but it is not possible to say whether such differences play a role in the natural history of the disease.

Differences from the normal were found in the serum proteins of coal workers suffering from pneumoconiosis which were similar to those in subjects suffereing from bronchitis, cancer and rheumatoid arthritis. The differences consisted of decreased albumin and increased globulin contents, and decreased sulphydryl contents, and decreased sulphydryl contents in both albumin and globulin proteins. These differences caused a reduction in the number of protein sulphydryl groups in serum. In pnemoconiotic coal workers the amount of idsulphide-linked cysteine in albumin increased above the normal, the increase tending to depend on the severity of the pneumoconiosis. Apart from this correlation the above differences could not be used to diagnose the class of pneumoconiosis.

In a comparative study, we examined 324 sera of the PiMM phenotype by isoelectric focusing. Sera were obtained from 254 healthy individuals, and from 70 patients suffering from chronic obstructive pulmonary disease (COPD). All individuals were examined, a detailed history and chest x-ray films were taken, and lung function tests were performed. The classification into PiMM subtypes according to a modified method, originally described by Genz et al, showed a significantly higher number of subtypes, containing more slowly migrating protein fractions (M2) in the group of patients. Since the prevalence of bronchitic symptoms is unusually common in industry, in workers who are exposed to dust and smoke tobacco, these findings are important, especially in regard to prophylactic measures in industry.