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The high incidence of children with recurrent episodes of acute obstructive bronchitis is a widespread problem. Correct identification of children at risk of developing bronchial asthma at school age may improve treatment and prevention approaches to this pathology, but the ability to identify these children remains limited. The purpose of the study was to determine the effectiveness of recombinant interferon alpha-2β in children with recurrent episodes of acute obstructive bronchitis in the course of treatment based on the assessment of cytokine profile. The study examined 59 children of the main group with recurrent episodes of acute obstructive bronchitis and 30 children of the comparison group who suffered from acute bronchitis, aged 2-8 years, who were in the hospital. The results of laboratory studies were compared with the data of 30 healthy children. In children with recurrent episodes of acute obstructive bronchitis, the content of serum interferon-γ and interleukin-4 was significantly reduced compared to healthy children, after treatment with recombinant human interferon alpha-2β, the content of interferon-γ and interleukin-4 in children significantly increased. The content of interleukin-1β in children with recurrent episodes of acute obstructive bronchitis was significantly higher than in healthy children, after immunomodulatory therapy with recombinant interferon alpha-2β, interleukin-4 normalized to its level in healthy children. It was found that children with recurrent episodes of acute obstructive bronchitis have an imbalance of cytokines, the effectiveness of recombinant human interferon alpha-2β therapy, which normalized the levels of the studied cytokines in the serum., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.

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 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 (C ss ) 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 C ss was 0.9 (0.2⁻2.9) mg/L, and C ss 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 C ss 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.

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.)

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.

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 (FEV 1 ) (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.

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.

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 Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Eosinophils are regarded as the major effector cells that produce symptoms in allergic diseases. Activation of eosinophils induces extracellular release of a number of eosinophil granule proteins, including major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin. The objective of this study was to evaluate the differences and significance of the sputum eosinophil% and expression levels of eosinophilic granule protein mRNAs in allergic airway disease. Induced sputum samples were obtained from non-smokers with 25 asthma, 54 eosinophilic bronchitis, 16 allergic rhinitis, and 19 healthy control subjects. The eosinophil granule protein mRNAs were measured with real time RT-PCR. There was no correlation between the sputum eosinophil% and the mRNA level of any of eosinophil granule proteins. However, the expression levels of MBP and ECP mRNAs were higher in subjects with each of the specified allergic diseases than those in control subjects (P < 0.05). Moreover, in the subjects with allergic sensitization, the expression levels of MBP and EPO mRNAs were significantly higher in those with airway hyperresponsiveness (13 subjects) than in those without airway hyperresponsiveness (32 subjects) (P = 0.004 and 0.010, respectively). In asthma patients, the FEV1% was negatively correlated with ECP mRNA levels (r = -0.510, P = 0.022), but showed no correlation with sputum eosinophil%. In conclusion, mRNA levels of eosinophil granule proteins, rather than sputum eosinophil%, may reflect airway hyperresponsiveness and airflow limitation. In practice, consideration for the eosinophil% as well as the eosinophil granule proteins levels in induced sputum is needed.

Brain natriuretic peptide (BNP) is a strong prognostic predictor in congestive heart failure patients. Community-acquired pneumonia (CAP) is frequently associated with systemic inflammatory response syndrome (SIRS), evolving into septic shock, with high mortality. The aim of this study was to compare BNP mean values in CAP, chronic obstructive pulmonary disease (COPD) exacerbation, and acute bronchitis patients, and to evaluate the correlation of BNP values with length of hospital stay. In all, we analysed 56 patients (28 males and 28 females) admitted to our Emergency Department from May 2010 to April 2011 because of dyspnea. The CAP patients had significantly higher mean BNP values in comparison to acute bronchitis patients (127.2 Vs 45.9 pg/mL; p=0.003), and a significantly positive correlation was found between their BNP values and length of hospital stay (r=0.404; p=0.05). A stepwise multivariate linear regression analysis model showed white blood cell count as the only independent predictor of length of hospital stay (p=0.05). The results suggest that CAP patients with SIRS have increased mean BNP levels compared to acute bronchitis patients, but this parameter failed to predict the length of hospital stay.

Asthma and nonasthmatic eosinophilic bronchitis (NAEB) are respiratory disorders characterized by a predominance of Th2 cells and eosinophilic inflammation. Suppressors of cytokine signaling (SOCS) proteins play an important role in Th2-mediated allergic responses through control of the balance between Th1 and Th2 cells, particularly, SOCS3 and SOCS5. The aim of this study was to analyze SOCS expression in human peripheral blood eosinophils from patients with asthma, NAEB and healthy controls. SOCS expression in eosinophils from subjects was demonstrated by different techniques. Results showed that expression of SOCS3 in eosinophils and CD4 T cells from patients was higher than in healthy subjects. In addition, we demonstrated that prostaglandin E₂ (PGE₂) and Th2 cytokines are able to upregulate SOCS3 production in eosinophils and attenuate its degranulation. In conclusion, eosinophils are able to transcribe and translate SOCS3 protein and can contribute to the regulation of the Th1/Th2 balance through SOCS3 production.

Objective: To compare concentrations of interleukin (IL)-4, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and total nitric oxide (NO) metabolites in bronchoalveolar lavage fluid (BALF) for discrimination between asthma and chronic bronchitis in cats., Animals: 97 cats., Procedures: Cats screened with cytologic examination of BALF included 13 client-owned cats with naturally developing asthma, 8 client-owned cats with chronic bronchitis, 23 research cats with experimentally induced asthma, 33 research cats with experimentally induced nonseptic suppurative inflammation of the airways, and 20 healthy control cats. Banked unconcentrated BALF supernatant samples were assayed for concentrations of IL-4, IFN-gamma, TNF-alpha, and total NO metabolites., Results: Concentrations of IL-4 and IFN-gamma in BALF were less than the limits of detection for most cats, precluding statistical analysis. No significant differences were detected among groups for TNF-alpha concentrations. Concentrations of total NO metabolites were significantly higher in cats with clinical chronic bronchitis, compared with research cats with nonseptic suppurative inflammation or research cats with asthma., Conclusions and Clinical Relevance: There were no significant differences in tested biomarkers between cats with asthma and healthy control cats. None of the measured cytokines or NO metabolites were useful for discriminating between cats with naturally developing asthma and those with chronic bronchitis.

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.

Aims: To assess the diagnostic value of lipopolysaccharide-binding protein (LBP) and fibrinogen compared to C-reactive protein (CRP) for pneumonia in primary care patients with lower respiratory tract infection (LRTI)., Methods: Receiver operating characteristic curves summarising test accuracies for LBP, fibrinogen and CRP for pneumonia were constructed. The respective areas under the curve (AUCs) were calculated and compared with that of body temperature, an acknowledged clinical sign to differentiate pneumonia from acute bronchitis in primary care., Results: 11 of 95 patients had radiographically confirmed pneumonia (11.7%). The AUC was 0.90 for CRP, 0.92 for LBP and 0.86 for fibrinogen. Body temperature yielded an AUC of 0.63. Differences between the AUCs were not significant for the three blood tests, but highly significant when compared to body temperature (p<0.001)., Conclusion: LBP and fibrinogen are equally strong predictors of pneumonia in patients with LRTI, but they do not perform better than CRP.

Background: In asthma interleukin (IL)-13 is increased in the airway compared with non-asthmatic eosinophilic bronchitis. Whether this differential expression is specific to the airway or is more generalised is uncertain., Methods: We sought to examine IL-13 expression in peripheral blood T-cells and eosinophils in asthma and non-asthmatic eosinophilic bronchitis. Peripheral blood CD3+ cell and eosinophil intracellular IL-13 expression from subjects with asthma, non-asthmatic eosinophilic bronchitis and healthy controls was assessed. The effect of priming by asthmatic serum on the release of IL-13 by peripheral blood mononuclear cells from healthy subjects was examined and the serum from these subjects was analysed for a range of chemokines and cytokines., Results: The median (IQR)% intracellular IL-13 expression by CD3+ cells was increased in asthma [5.3 (2.7-9.8)%; n = 12] compared to non-asthmatic eosinophilic bronchitis [1.1 (0.5-3)%; n = 7] and healthy controls [1.7 (0.2-3%); n = 9] (p = 0.02), but was not significantly different in eosinophils across the groups. IL-13 released from healthy peripheral blood mononuclear cells (n = 10) was increased by asthmatic serum [117 (47.8-198)pg/ml] compared to control [78.5 (42.6-128)pg/ml; p = 0.02), but was not affected by non-asthmatic serum., Conclusion: Our findings support the view that IL-13 expression is increased in peripheral blood-derived T cells in asthma and that asthmatic serum up-regulates IL-13 release from healthy peripheral blood mononuclear cells.

Vascular endothelial growth factor (VEGF) is produced by a wide range of cells and plays an important role in normal and pathological angiogenesis. The formation of the vascular system is essential for inflammatory process in airways, especially in the course of chronic lung diseases - for example bronchial asthma. Increased level of VEGF in serum and induced sputum has been demonstrated in patients with stable asthma, as well as during the exacerbation of this disease. VEGF end VEGF-receptor's expressions is closely correlated with neovascularization and seems to be an important predictor of the lung's remodeling. Due to direct causative relationship between inflammatory process and angiogenesis in airways, it was suggested, that inhibiting VEGF's activity would have an anti-inflammatory effect on airways. In this article the potential role of vascular endothelial growth factor in airways inflammation, remodeling and the clinical course of bronchial asthma is presented.

Objective: To analyse the mid region of plasma N-terminal pro-atrial natriuretic peptide (MR-proANP) levels in patients with lower respiratory tract infections to evaluate its prognostic use for the severity of disease and outcome., Design: Prospective observational study. Setting. Emergency department of a university hospital., Subjects: A total of 545 consecutive patients with lower respiratory tract infections and 50 healthy controls. Interventions. MR-proANP was measured in serum from all patients using a new sandwich immunoassay., Results: MR-proANP levels (median [IQR], in pmol L(-1)) were significantly higher in patients with lower respiratory tract infections when compared with controls (138.0 [74.1-279.0] vs. 72.7 [62.5-89.5], P < 0.001), with highest levels in patients with community-acquired pneumonia (CAP). MR-proANP, but not C-reactive protein (CRP) levels, gradually increased with increasing severity of CAP, classified according to the pneumonia severity index (PSI) score (P < 0.001). On admission, MR-proANP levels were significantly higher in nonsurvivors when compared with survivors (293.0 [154.0-633.0] vs. 129.0 [71.4-255.0], P < 0.001). In a receiver operating characteristic (ROC) analysis for the prediction of survival of patients with CAP the area under the ROC curve (AUC) for MR-proANP was 0.69, similar when compared with the PSI (AUC 0.74, P = 0.31), and better when compared with other biomarkers, i.e. procalcitonin (AUC 0.57, P = 0.08), CRP (AUC 0.52, P = 0.02), and leucocyte count (AUC 0.56, P = 0.07)., Conclusions: MR-proANP levels are increased in lower respiratory tract infections, especially in CAP. Together with other clinical, radiographic and laboratory findings, MR-proANP levels might be helpful for the risk stratification in CAP.

Objective: This study aimed to evaluate the adverse effects of extensively hydrolyzed milk formula on growth in infants and toddlers., Methods: Prospectively, 45 infants and toddlers with a positive history of cow's milk allergy confirmed by positive skin prick test and high IgE levels for either alpha-lactalbumin, beta-lactoglobulin, or casein and positive single-blind food challenge received extensively hydrolyzed milk formulas for 1 year. Sex-normalized percentiles of heights and weights of infants and toddlers before their enrollment in the study were compared to those at the end of the study. The contribution of breastfeeding, early use of bottle feeding and intake of adapted or special milk formulas, and history of bronchitis and atopic dermatitis on toddlers' growth were also evaluated by multivariate analysis., Results: Similar percentiles of the children's weight and height were observed at the beginning of the study and 1 year later. According to the multivariate analysis, sex, breastfeeding, early bottle feeding, ingestion of adapted or special milk formulas, atopic dermatitis, and bronchitis were not correlated with either the children's weight or height at diagnosis of the allergy or at 1 year of follow-up (P > .10). Weights and heights were not different between toddlers who had atopic dermatitis or bronchitis during the study period and those who did not., Conclusions: Growth of infants and toddlers with cow's milk allergy was not affected by the intake of extensively hydrolyzed milk for 1 year. Atopic dermatitis and bronchitis did not appear to have any deleterious effect on these children's growth.

Objective: To investigate the protective effects of beta-carotene in rats against the development of chronic bronchitis induced by cigarette smoking., Methods: Forty-two Male Wistar rats were randomly divided into three study groups: (1) control (n = 15), animals underwent no treatment; (2) cigarette smoking (n = 15), animals developed chronic bronchitis through long-term cigarette smoking twice a day for 75 d; (3) beta-carotene plus cigarette smoking animals (n = 12) were given 1 ml or 15 mg/kg beta-carotene orally every day just before cigarette smoking. The levels of IL-6, IL-8, NO, superoxide dismutase (SOD) and lipoperoxide (LPO) in serum, bronchoalveolar lavage fluid (BALF) and lung tissue were measured and the pathological changes to lung tissue were analyzed using light microscopy., Results: Long-term cigarette smoking caused an obvious increase in the amount of IL-6, IL-8 and LPO and a sharp decrease in the levels of NO and SOD in smoking animals compared to controls. beta-carotene intake reversed all the changes induced by smoking and alleviated the pathological changes caused by chronic bronchitis., Conclusions: Quantitative oral intake of beta-carotene had protective effects against chronic bronchitis induced by long-term cigarette smoking, which was associated with the increased production of NO, the clearance of some oxidative free radicals (OFR) and the alleviation of chronic inflammation.

alpha1-Antitrypsin (AAT) deficiency predisposes to bronchitis and emphysema associated with neutrophilic airway inflammation. The efficacy of augmentation therapy has not been proven clinically or by demonstrating an effect on airway inflammation. We treated 12 patients with four infusions of Prolastin (60 mg/kg) at weekly intervals and monitored both the serum and secretion concentrations of AAT as well as markers of neutrophilic inflammation, including myeloperoxidase, elastase, and the neutrophil chemoattractants interleukin-8 and leukotriene B(4). Serum AAT rose and was maintained above the protective threshold. In addition, AAT concentrations in the sputum rose from a mean of 0.17 microM (SEM +/- 0.04) before therapy to concentrations similar to nondeficient subjects (0.43 +/- 0.12) 1 week after the first infusion (p < 0.01). This was associated with a reduction in elastase activity (p < 0.002) and the chemoattractant leukotriene B(4) (p < 0.02), which fell from a median baseline value of 13.46 nM (range, 4.17-55.00) to 8.62 nM (4.23-21.59) the day following the last infusion. Although median values for myeloperoxidase and interleukin-8 also fell, the changes failed to achieve statistical significance. In summary, short-term therapy with AAT increased lung secretion concentrations and was associated with a fall in leukotriene B(4), which is thought to be central to the airway inflammation of AAT deficiency.

Background: Tobacco smokers have lower serum levels of IgG than non-smokers. IgG subclass deficiency is common in patients with recurrent respiratory infections. Recurrent bronchial infections are common in smokers with chronic bronchitis (CB). We have investigated whether susceptibility to recurrent exacerbations in smokers with CB is associated with altered IgG subclass levels or IgG subclass deficiency., Methods: Serum levels of IgG, IgA, IgM, and IgG subclasses 1-4 were determined by radial immunodiffusion in 100 subjects: 33 smokers with stable CB and recurrent exacerbations, 24 asymptomatic smokers, and 43 healthy never smokers. Systemic tobacco exposure was verified and excluded using a serum cotinine ELISA. Immunoglobulin data were log transformed to enable use of parametric statistical methods., Results: Compared with never smokers, both patients with CB and asymptomatic smokers had significantly lower levels of IgG (median 9.7 g/l (range 5.6-15.2) and 9.9 (6.1-12.1) g/l v 12.0 (6.9-18.5) g/l) and IgG2 (2.8 (0.9-5.9) g/l and 2.5 (1.0-6.3) g/l v 4.0 (1.7-10.2) g/l). The estimated ratio of median values between the patients with CB and never smokers was 0.78 (95% confidence interval (CI) 0.69 to 0.89) for IgG and 0.65 (95% CI 0.50 to 0.83) for IgG2. The corresponding ratios between asymptomatic smokers and never smokers were 0.79 (95% CI 0.69 to 0.91) and 0.60 (95% CI 0.50 to 0.83), respectively. There were no significant differences between the smoking groups., Conclusions: Susceptibility to recurrent exacerbations in smokers with CB is not associated with lower levels of IgG subclasses than can be accounted for by smoking per se.

Background: Acute bronchitis is one of the most common illnesses treated in the primary care setting. Most patients are treated with antibiotics, despite the fact that acute bronchitis is often a viral infection. There is little evidence that antibiotics are of any value in the treatment of this illness. Inappropriate use of antibiotics in the treatment of this and other infectious diseases contributes to the development of resistant bacteria. The purpose of this study was to reduce the prescribing of antibiotics for acute bronchitis in patients without underlying lung disease in the acute care clinic in Arendal, Norway., Material and Methods: The study had three phases, the first of which was a pilot study showing that 87% of patients with acute bronchitis received a prescription for antibiotics. The next phase was an educational intervention in which the physicians were informed of the inappropriately high prescribing rate, the lack of evidence that antibiotics are useful in the treatment of acute bronchitis, and the potential of C reactive protein (CRP) in the diagnose of this illness. The third phase of the study examined the treatment given to patients after the intervention., Results: The antibiotic prescribing rate was reduced from 87% to 71% after the intervention. Doxycycline was prescribed most often, followed by penicillin and erythromycin. The use of CRP increased, and the rate of antibiotic prescriptions for patients with CRP < or = 20 was reduced after the intervention. There were fewer bronchitis diagnoses and more pneumonia diagnoses made after the intervention., Interpretation: An educational intervention designed for prescribing doctors may reduce the use of antibiotics in the treatment of acute bronchitis.

Pulmonary tuberculosis, one of the granulomatous diseases, has few serological markers for its activity. Recently, an increased serum level of vascular endothelial growth factor (VEGF) was detected in patients with Crohn's disease, also a granulomatous disease. We hypothesized that VEGF might be associated with the pathogenesis of pulmonary tuberculosis. We investigated the serum level of VEGF in 43 patients with active pulmonary tuberculosis, 29 patients with old tuberculosis, and 25 patients with acute bronchitis. We were able to examine the serum VEGF levels every 3 mo for a period of 6 mo in seven patients with active pulmonary tuberculosis. We examined the presence of VEGF in the resected lungs of three patients with active pulmonary tuberculosis by immunohistochemistry. The serum levels of VEGF were significantly higher in patients with active pulmonary tuberculosis than in patients with old tuberculosis and acute bronchitis. The decrease in titer of serum VEGF paralleled the clinical improvement of patients with pulmonary tuberculosis. Immunohistochemical staining of the resected lungs demonstrated the presence of VEGF in alveolar macrophages surrounding the lesion. Therefore, VEGF may be associated with the pathogenesis of pulmonary tuberculosis.

Chronic obstructive pulmonary disease (COPD) is a syndrome of chronic wasting, in part associated with a chronic inflammatory response. The aim of this study was to investigate cross-sectionally and prospectively the potential role of leptin in relation to systemic inflammation in the regulation of the energy balance in COPD. Body composition by deuterium dilution, resting energy expenditure (REE) by indirect calorimetry, and plasma concentrations of leptin and soluble tumor necrosis factor (TNF) receptors (sTNF-R) 55 and 75 by ELISA were measured in 27 male patients with emphysema and 15 male patients with chronic bronchitis (disease-subtype defined by high-resolution computed tomography [HRCT]). Emphysematous patients were characterized by a lower body mass index due to a lower fat mass (FM) (p = 0.001) and by lower mean (detectable) leptin concentrations (p = 0.020) compared with bronchitic patients. Leptin was exponentially related to FM in emphysema (r = 0.74, p < 0.001) and in chronic bronchitis (r = 0.80, p = 0.001). Furthermore, a significant partial correlation coefficient between leptin and sTNF-R55 adjusted for FM and oral corticosteroid use was seen in emphysema (r = 0.81, p < 0.001) but not in chronic bronchitis. In 17 predominantly emphysematous depleted male patients with COPD, baseline plasma leptin divided by FM was in addition logarithmically inversely related to baseline dietary intake (r = -0.50, p = 0.047) and to the degree of weight change after 8 wk of nutritional support (r = -0.60, p = 0.017). This proposed cytokine-leptin link in pulmonary cachexia may explain the poor response to nutritional support in some of the cachectic patients with COPD and may open a novel approach in combating this significant comorbidity in COPD. Schols AMWJ, Creutzberg EC, Buurman WA, Campfield LA, Saris WHM, Wouters EFM. Plasma leptin is related to proinflammatory status and dietary intake in patients with chronic obstructive pulmonary disease.

Moraxella catarrhalis is an important cause of otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). Outer membrane protein CD (OMP CD) is a 45-kDa protein which is a potential vaccine antigen to prevent infections caused by M. catarrhalis. Eight monoclonal antibodies were used to study the antigenic structure of the OMP CD molecule by assaying recombinant peptides corresponding to the sequence of the protein. This approach identified two surface-exposed epitopes, including one near the amino terminus (amino acids 25 to 44) and one in the central region of the molecule (amino acids 261 to 331). Assays with serum and sputum supernatants of adults with COPD revealed variable levels of antibodies to OMP CD among individuals. To determine which portions of the OMP CD molecule were recognized by human antibodies, three human serum samples were studied with six recombinant peptides which span the sequence of OMP CD. All three sera contained immunoglobulin G antibodies which recognized exclusively the peptide corresponding to amino acids 203 to 260 by immunoblot assay. Adsorption experiments with whole bacteria established that some of the human antibodies are directed at surface-exposed epitopes on OMP CD. We conclude that OMP CD is a highly conserved molecule which contains at least two separate epitopes which are exposed on the bacterial surface. While individual adults with COPD show variability in the immune response to OMP CD, a specific region of the OMP CD molecule (amino acids 203 to 260) is important as a target of the human immune response.

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.

Increased serum levels of mucin-associated antigen have been previously demonstrated in patients with cystic fibrosis (CF) and interstitial pneumonia, and in lung-transplant recipients. The present study assessed the serum airway mucin levels in patients with acute respiratory distress syndrome (ARDS). An enzyme-linked immunosorbent assay (ELISA) method with a human-airway-mucin-specific monoclonal antibody (17Q2) was used to measure serum mucin levels in normal subjects, chronic smokers, patients with chronic bronchitis and other pulmonary diseases, patients with acute cardiogenic lung edema, and patients with ARDS. The serum mucin levels measured 9.9 +/- 0.8 ng/ml (mean +/- SEM, n = 59) in normal subjects, 12.7 +/- 1.6 ng/ml (n = 29) in chronic smokers, 21.8 +/- 1.9 ng/ml (n = 28) in patients with chronic bronchitis and other pulmonary diseases, 9.0 +/- 3.1 ng/ml (n = 5) in patients with acute cardiogenic lung edema. The serum mucin level was 53.8 +/- 6.6 ng/ml (n = 13) in patients with ARDS (p < 0.05, as compared with the four other groups). Serial measurements of serum mucin levels were obtained in patients with ARDS. Statistical analysis showed an inverse correlation of serial measurements of serum mucin with static respiratory-system compliance (p = 0.021), an inverse correlation of sequential serum mucin levels and log(Pa(O2)/Fl(O2)) (p = 0.016), and a positive correlation of sequential serum mucin levels and lung injury score (LIS) (p = 0.019). Gel-filtration analysis showed that mucin-associated antigens in ARDS sera were polydispersed and smaller than the antigens in normal sera. This study indicates that an increasing amount of degraded mucin occurs in patients with ARDS.

Objective: To investigate how close we can come to the aetiology of acute bronchitis in adults in a primary care setting., Design: Prospective study., Setting: General practice population in Gardabaer district, south-western Iceland., Subjects: 140 patients > or = 16 years old who were diagnosed as having acute bronchitis during a two-year period (1992-1993)., Main Outcome Measures: Laboratory investigations (twice with a minimum four-week interval), used in general practice to analyse respiratory tract infections. They included serology for Chlamydia pneumoniae, Mycoplasma pneumoniae, respiratory tract viruses, and the level of C-reactive protein., Results: Of a total of 140 patients, two blood samples were taken on scheduled time in 113 patients. Serology confirmed recent infection in 18 (16%) of these patients. Only two (2%) had a bacterial infection (one C. pneumoniae, one M. pneumoniae). The others (84%) did not have a significant increase in antibody titres. Only four (4%) had C-reactive protein levels higher than 48 mg/l., Conclusions: The study indicates that it is difficult to come close to a precise aetiology with respect to infectious agents of acute bronchitis in general practice. We conclude that the disease is rarely caused by atypical bacteria such as C. pneumoniae and M. pneumoniae, and rarely caused by bacterial infections severe enough significantly to increase the level of C-reactive protein.

Serum secretory leukoprotease inhibitor (SLPI) is synthesized and secreted by serous cells in airway glands, and the serum level is speculated to reflect airway gland hyperplasia. To test this hypothesis, we measured the serum SLPI in 38 clinically stable patients with chronic bronchitis (3F and 35M; 58 +/- 2 years, mean +/- S.E.M.) (group CB), 24 patients with Sjögren's syndrome (24F; 52 +/- 3 years) (group SG), and compared it with 12 healthy control subjects (6F and 6M; 54 +/- 3 years) (group CN) using an enzyme-linked immunosorbent assay (ELISA). The serum SLPI from group CB (105 +/- 8 ng/ml) was significantly higher than that from group CN (60 +/- 2 ng/ml) and further, it significantly correlated with sputum volume per day. Although the mean value of serum SLPI from group SG (64 +/- 5 ng/ml) was not different from that from group CN, serum SLPI significantly correlated with the duration of respiratory symptoms (cough and/or sputum) in group SG. In conclusion, serum SPLI level reflects airway gland hyperplasia, suggesting that SLPI measurement is a possible laboratory method to estimate airway glandular hyperplasia.

The possibility of nocturnal oxygen desaturation (NOD) in patients with chronic bronchitis and emphysema (CBE) even with basal hypoxemia greater that 55 mmHg is well recognised. Nocturnal hypoventilation is admitted as the main cause for this NOD. In this study we evaluate how the presence of left ventricular dysfunction (LVD) could aggravate NOD. Thirty-six patients with CBE and basal stabilised PaO2 55-70 mmHg underwent right heart catheterisation and polysomnographic study. NOD was defined as more than 30% of total sleep time with SaO2 less than 90%; LVD was defined as capillary pressure greater than 15 mmHg. Six patients were excluded from analysis because of sleep apnoea syndrome. In the remaining 30 patients (20 men, 10 women; mean age = 65.88.6 years; mean FEV1 = 0.970.31 litres; 43.316.6% predicted; mean basal PaO2 = 61.83.6 mmHg) 8 had LVD and 18 and NOD. Patients with NOD had a greater diurnal level of hypoventilation (basal PaCO2 = 44.63.8 vs. 414.1 mmHg; p = 0.025). Patients with LVD, despite identical diurnal pulmonary function, showed a significantly p < 0.05) greater degree of NOD (mean nocturnal SaO2 = 84.56.4 vs 89.52.5; minimal nocturnal SaO2= 68.517.3 vs. 79.47.8; Time spent with SaO2 < 90% = 78.833.7 vs. 43.138.7). We conclude that the presence of LVD in patients with CBE and PaO2 55-70 mmHg aggravates the intensity and the time spent with NOD, probably because of aggravation of hypoventilation or ventilation/perfusion mismatching.

We report here a case of thromboembolism occurring in a 29-year-old woman with transient eosinophilia. Eosinophilia for at least 11 days was followed by pulmonary embolism. Both reperfusion of pulmonary arteries and disappearance of deep vein thrombi were obtained by treatment with urokinase, tissue plasminogen activator, and heparin. Although the causes of eosinophilia were not specified, we suggested a causative correlation of elevated serum levels of eosinophil granule proteins with the development of thromboembolism.

The aim of this study was to assess the effects of diamorphine on breathlessness and exercise tolerance in patients with severe chronic airflow obstruction and normal arterial carbon dioxide tension (PCO2) levels ("pink puffer" syndrome). In this double-blind, cross-over, randomized study we examined both acute and chronic effects of single and multiple doses of oral diamorphine in 14 "pink puffer" patients. Their mean resting forced expiratory volume in one second (FEV1) was 36% predicted normal, mean arterial oxygen tension (PaO2) was 9.2 kPa and mean PaCO2 was 5.2 kPa. Ten patients took either diamorphine 2.5 or 5 mg or placebo elixir 6 hourly for 2 weeks, recording on a diary card dyspnoea, sleepiness and well-being on a visual analogue scale (VAS). The final treatment was given 30 min before measuring spirometry, arterial blood gases, plasma morphine levels, 6 min walking distances, time walked on treadmill and self-assessment of dyspnoea on a VAS scale after exercise. On two further days, eight patients took two doses, 4 h apart, of either diamorphine 7.5 mg or placebo elixir. Spirometry, 6 min walking distance with a VAS score for dyspnoea were measured before and at 1 h after each dose. Morphine levels and blood gases were also measured. Whether given in single or repeated doses, oral diamorphine had no significant effect on exercise tolerance and breathlessness when compared with placebo. Diamorphine 2.5-7.5 mg produced neither sleepiness nor a deterioration in blood gases. However, plasma levels associated with analgesic efficacy were not achieved with these doses. Thus, as given in this study, oral diamorphine is unlikely to have therapeutic potential in the treatment of dyspnoea in the "pink puffer" syndrome.

Recurrent pulmonary infections with Staphylococcus aureus and Pseudomonas aeruginosa are a major problem in cystic fibrosis (CF), leading to severe and progressive deterioration of the respiratory tract. Fibronectin (FN) has a binding site(s) for S. aureus and Streptococcus pyogenes. This bacterial bindings site(s) was studied by using FN from patients with CF and comparing them with FN purified from the plasma of bronchitis and normal subjects by an enzyme-linked immunosorbent assay technique. We found a decreased binding of the CF FN to these bacteria in all seven CF patients. Other differences between the CF FN and normal FN were a marked modification in the pattern of peptide migration in polyacrylamide gel electrophoresis after hydrolysis with various proteinases and an increase or decrease of the total sugar content of the FN.

In more than a thousand chronic obstructive lung disease (COLD) patients we have observed in six cases, that exercise-induced hypercapnia was accompanied by a concomitant improvement in arterial oxygen tension (PaO2) and a decrease in the alveolo-arterial O2. This behaviour was not due to technical errors. We explained the increase in PaO2 during exercise by three nonmutually exclusive mechanisms: 1) an increase in the respiratory quotient; 2) the exercise induced increase in alveolar ventilation, although inadequate to match the increase in CO2 production, would be redistributed to previously poorly ventilated regions of the lung, these regions therefore receiving enough oxygen to arterialize the blood flowing through the alveolar capillaries; 3) alternatively, perfusion would be redistributed in a more efficient way during exercise, so that even in the presence of hypoventilation, oxygenation would be improved.

Twenty patients with chronic bronchitis were given incremental dosages of a new slow release preparation of theophylline and observed for its effect on lung function and exercise tolerance. Measurements were made subjectively by using visual analogue scales and objectively using six minute walking distances and spirometry. The study was placebo controlled and had a double blind randomised design. In the dosages used (200, 400, 600, and 800 mg) theophylline produced no significant improvement in forced expiratory volume in one second or forced vital capacity, and there was no overall improvement in peak expiratory flow rate. Similarly, neither effort tolerance nor degree of breathlessness appeared to be influenced by the drug, even when unacceptably high dosages were used. By contrast, placebo yielded a 7% increase in the six minute walking distance. From these results it seems difficult to justify the routine, indiscriminate use of theophylline for chronic bronchitis.

In a cross-over study, 10 healthy adult volunteers received 1 g cefaclor and 1 g cephalexin orally 1 hour after a standard breakfast. Serum levels of cefaclor rose somewhat faster and were higher than those of cephalexin in the first 60 minutes. At the end of the second hour the serum concentration of cephalexin was 50--100% higher. The area under the serum level curve averaged 45 hr-micrograms/ml for cefaclor and 60 hr-micrograms/ml for cephalexin. Calculated pharmacokinetic constants indicate that the absorption rate of cefaclor was nearly the same as that of cephalexin. The serum half-life of cefaclor was 1 hr. The urine recovery of cefaclor for 9 hours averaged 65%, whereas cephalexin resulted in a urine recovery of 85%. To evaluate sputum levels, 15 adult patients with bronchial carcinoma and secondary bronchitis or pneumonia were treated with 0.5 g of cefaclor orally 4 times daily. The mean individual sputum levels were 0.44 micrograms/ml (after the first dose) and 0.54 micrograms/ml (after repeated administration). In 10 other patients, after a single 1 g dose of cefaclor mean sputum levels after 1 hour and 3 hours doubled, whereas peak concentrations in sputum after 2 hours did not differ significantly. These results suggest that cefaclor will be useful in respiratory tract infections caused by sensitive bacteria.

Peripheral blood leucocyte counts, and E binding rosettes were measured on 138 men on five separate occasions. Little effect was seen from age, or length of asbestos exposure. Overall the most marked effect was that obtained from smoking. Most relevant was an increase in percentage of E-rosettes read after 1 1/2 hrs, which was obtained in the group of those with radiological evidence of fibrosis who smoked. Restricted to subjects with small opacities, those who smoke have a significantly higher (P less than 0.05) percentage E 1 1/2 hr rosettes than those who do not smoke. (Percentage E rosettes read overnight remained unaltered by smoking or X-ray). This increase was found on each occasion that it was measured. Since the absolute number of T lymphocytes rosetting at 1 1/2 hr did not increase, it is suggested that there is either no stimulation of the central pool of T lymphocytes or a decrease in the absolute number of T lymphocytes which could only rosette overnight.

Changes in blood gas tensions occurring when 100% oxygen or air was used as the driving gas for nebulised salbutamol were studied in 23 patients with severe airways obstruction. The patients fell into three groups: nine had chronic bronchitis and emphysema with carbon dioxide retention, seven had emphysema and chronic bronchitis without carbon dioxide retention, and seven had severe asthma (no carbon dioxide retention). When oxygen was used as the driving gas patients who retained carbon dioxide showed a mean rise of 1.03 kPa (7.7 mm Hg) in their pressure of carbon dioxide (Pco2) after 15 minutes (p less than 0.001) but the Pco2 returned to baseline values within 20 minutes of stopping the nebuliser. The other two groups showed no rise in Pco2 with oxygen. When air was used as the driving gas none of the groups became significantly more hypoxic. Although it is safe to use oxygen as the driving gas for nebulisers in patients with obstructive airways disease with normal Pco2, caution should be exercised in those who already have carbon dioxide retention.

The serum S-IgA levels of 33 patients with diffuse panbronchiolitis (DPB) were compared with those of 13 patients with chronic bronchitis (CB) and 24 patients with bronchiectasis (BE), to obtain information on differences in the pathologic states in DPB and other chronic bronchial diseases. The S-IgA levelw as elevated in all three bronchial diseases, being significantly higher in DPB than in CB, and intermediate in BE. Persistent bacterial infections developed in most of the patients with DPB and two-thirds of those with BE, but in few of those with CB. Serum S-IgA levels were especially high in patients expectorating Pseudomonas aeruginosa-positive sputum, who constituted two-thirds of the patients with DPB and about one-third of those with BE. The highest levels over (100 micrograms/ml) were observed in far-advanced patients with DPB who expectorated P. aeruginosa-positive sputum. The increase in the serum level of IgA was less than that of S-IgA in all three diseases. These results indicate that the marked elevation of the serum S-IgA level in patients with DPB is due to extensive, chronic infection of the airways of the lungs, especially the peripheral airways, and that serum S-IgA is a useful marker for determining the clinical stage and the pathologic state of patients with diffuse peripheral airway diseases.

Corticosteroids caused a reduction in the ratio of sol-phase sputum concentration to serum concentration of albumin in 12 patients with chronic obstructive bronchitis, suggesting a reduction in protein transudation. Alpha-1-antitrypsin values followed the same pattern as those of albumin in both the control and treatment periods, confirming the similar behaviour of the two proteins. The alpha 1-antichymotrypsin ratios were on average three times higher than those of albumin in the control period, confirming the presence of local mechanisms in the lung for preferentially concentrating this protein. The sputum-to-serum ratio of alpha 1-antichymotrypsin, however, rose during steroid treatment with the result that there was a selective increase in this protease inhibitor, which may be of potential benefit to such patients.

An increasing work rate was performed by 40 patients with chronic obstructive bronchitis, split into two groups according to FEV1 (group M, mean FEV1 1-451. and group S, mean FEV1 0-621.), and by 20 normal, non-athletic men of similar age to the patients. Values for cardiac frequency and ventilation were interpolated to standard oxygen uptakes of 0-75, 1-0, and, where possible, 1-5 min-1. The tidal volume at a ventilation of 20 and 30 1 min-1 was also determined. The cardiac frequencies at oxygen uptake of 0-75 and 1-01 min-1 were significantly higher in the patient groups than in the normal men, and were highest in patient group S. The cardiac output when related to the oxygen uptake was in the normal range in all three groups of subjects, so that the patients had smaller stroke volumes than the normal men. Ventilation at oxygen uptakes of 0-75 and 1-01 min-1 was significantly higher in both patient groups than in the normal subjects; there were no significant differences between the two patient groups, Values for dead space/tidal volume ration, alveolar-arterial oxygen gradient, and the percent venous admixture measured during a constant work rate test were significantly greater than normal in the patient groups. Possible factors limiting exercise tolerance in these patients were assessed by extending the increasing work rate test from submaximum to maximum exercise. Changes in blood gas tensions and blood lactate concentrations from resting levels were small, and probably did not limit exercise performance. Measurements at maximum exercise did not add appreciably to the analysis of the disturbed cardiopulmonary function. This study has shown that major disturbances in cardiopulmonary function can be demonstrated without the need for stressing a patient to the limit of his effort tolerance.

A detailed pharmacokinetic study of cefuroxime has been carried out. Levels of cefuroxime were determined in the blood, sputum, saliva, and urine of 23 patients receiving parenteral cefuroxime eight hourly for chest infections. Profiles were obtained after the first dose and on the final (fifth) day of treatment. Antibiotic levels in the sputum reached 0.8 mg/l within one hour of the first injection, and were maintained close to this value for six hours. There was a build-up by the fifth day, mean cefuroxime concentrations at this time reaching 1.8 mg/l. This concentration was maintained for a prolonged period. Salivary concentrations were detectable but low (maximum mean value was 0.6 mg/l). Concentrations of antibiotic were significantly higher in the serum than those observed after the same doses in volunteers. In the patients there was no build-up in serum levels between the first and fifth days. The data obtained explain the clinical efficacy of cefuroxime in the treatment of lower respiratory infections, and suggest that a 12-hour schedule may be feasible.