bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cough augmentation with mechanical insufflation/exsufflation in patients with neuromuscular weakness
Authors: Chatwin M. , Ross E. , Hart N. , Nickol A.H. , Polkey M.I. , Simonds A.K. 
Published: September 2008

Adults and children with neuromuscular disease exhibit weak cough and are susceptible to recurrent chest infections, a major cause of morbidity and mortality. Mechanical insufflation/exsufflation may improve cough efficacy by increasing peak cough flow. It was hypothesised that mechanical insufflation/exsufflation would produce a greater increase in peak cough flow than other modes of cough augmentation. The acceptability of these interventions was also compared.Twenty-two patients aged 10–56 yrs (median 21 yrs) with neuromuscular disease and 19 age-matched controls were studied. Spirometry was performed and respiratory muscle strength measured. Peak cough flow was recorded during maximal unassisted coughs, followed in random order by coughs assisted by physiotherapy, noninvasive ventilation, insufflation and exsufflation, and exsufflation alone. Subjects rated strength of cough, distress and comfort on a visual analogue scale.In the neuromuscular disease group, mean±sd forced expiratory volume in one second was 0.8±0.6 L·s−1, forced vital capacity 0.9±0.8 L, maximum inspiratory pressure 25±16 cmH2O, maximum expiratory pressure 26±22 cmH2O and unassisted peak cough flow 169±90 L·min−1. The greatest increase in peak cough flow was observed with mechanical insufflation/exsufflation at 235±111 L·min−1(p<0.01). All techniques showed similar patient acceptability.Mechanical insufflation/exsufflation produces a greater increase in peak cough flow than other standard cough augmentation techniques in adults and children with neuromuscular disease.
Chlorine inhalation produces nasal congestion in allergic rhinitics without mast cell degranulation
Authors: Shusterman D. , Balmes J. , Avila P.C. , Murphy M.A. , Matovinovic E. 
Published: September 2008

Seasonal allergic rhinitic (SAR) subjects are more sensitive to nasal irritants than nonrhinitic (NR) subjects; however, the mechanism underlying this difference is unclear. This study sought to determine whether irritant-induced nasal congestion involves mast cell degranulation.Eight SAR and eight NR subjects were exposed to both 1.0 parts per million chlorine and filtered air in separate visits; exposures werevianasal mask and lasted 15 min. Rhinomanometry was performed before, immediately after and 15 min after exposure. Following ≥2 weeks, exposures and symptom reporting were repeated with nasal lavage, rather than rhinomanometry, pre- and postexposure. A separate substudy using rye grass antigen provided a positive control. Mast cell tryptase was measured in nasal lavage fluid from both substudies using an automated fluoroenzyme immunoassay.Chlorine provocation significantly increased nasal airway resistance in SAR but not NR subjects. Conversely, tryptase levels in nasal lavage fluid were unaffected. Nasal allergen challenge significantly increased both nasal obstruction and nasal lavage tryptase in SAR subjects.Irritant-induced nasal congestion is more pronounced among seasonal allergic rhinitic than nonrhinitic subjects. However, unlike nasal allergen challenge, the mechanism of response to chlorine does not appear to involve mast cell degranulation.
Effects of erythromycin onPseudomonas aeruginosaadherence to collagen and morphologyin vitro
Authors: Tsang K.W. , Ng P. , Ho P.L. , Chan S. , Tipoe G. , Leung R. , Sun J. , Ho J.C. , Ip M.S. , Lam W.K. 
Published: September 2008

The airways of patients with bronchiectasis and cystic fibrosis are often chronically colonised byPseudomonas aeruginosa(PA), which is virtually impossible to eradicate. Low-dose erythromycin (EM), for unknown mechanisms, is efficacious in bronchiectasis and diffuse panbronchiolitis.In this study, anin vitromodel to investigate PA adherence to human type IV basement collagen was developed by using scanning electron microscopy (SEM). There were significantly less PA bacilli per 20 random SEM fields (4,000×) when PA was cultured in 0.05, 0.5 and 5 µg·mL−1of EM compared with control (absence of EM). Adherence density (20 SEM fields·log−1inocular size) for PA obtained from no EM (56.8±43.16) was significantly higher than that obtained from 0.05, 0.5, and 5 µg·mL−1EM (21.5±17.56, 23.3±16.65, and 21.4±12.65 respectively). By using SEM it was found that PA, when incubated in EM (0.05, 0.5, 5 µg·mL−1) had a significant reduction in its diagonal length, radius, height, volume and surface area.It is possible, therefore, that these misshapedPseudomonas aeruginosabacilli are more susceptible to host defence mechanisms, while at the same time less adherent to the basement membrane of the airwayin vivo. Therefore, this could help explain the clinical efficacy of low-dose erythromycin therapy on patients withPseudomonas aeruginosainfection.
Tumour necrosis factor family genes in a phenotype of COPD associated with emphysema
Authors: Ferrarotti I. , Zorzetto M. , Beccaria M. , Gilè L.S. , Porta R. , Ambrosino N. , Pignatti P.F. , Cerveri I. , Pozzi E. , Luisetti M. 
Published: September 2008

Genetic factors are believed to play a role in the individual susceptibility to chronic obstructive pulmonary disease (COPD). Tumour necrosis factor (TNF) family genes have been widely investigated but inconsistent results may lie either in the genetic heterogeneity of populations or in the poor phenotype definition. A genetic study was performed using a narrower phenotype of COPD.The authors studied 86 healthy smokers and 63 COPD subjects who were enrolled based on irreversible airflow obstruction (forced expiratory volume in one second/forced vital capacity <70% predicted) and a diffusing capacity for carbon monoxide <50% predicted (moderate-to-severe COPD associated with pulmonary emphysema). The following polymorphisms were investigated: TNF-308, the biallelic polymorphism located in the first intron of the lymphotoxin‐α gene, and exon 1 and exon 6 of the TNF receptor 1 and 2 genes, respectively.No significant deviations were found concerning the four polymorphisms studied between the two populations.The authors confirm that the tumour necrosis factor family genes, at least for the polymorphisms investigated, are not major genetic risk factors for chronic obstructive pulmonary disease in Caucasians, either defined in terms of emphysema (this study) or airflow obstruction (previous studies). Nevertheless, the authors would like to emphasise the importance of narrowing the phenotype in the search for genetic risk factors in chronic obstructive pulmonary disease.
Reduced lung function and risk of atrial fibrillation in The Copenhagen City Heart Study
Authors: Buch P. , Friberg J. , Scharling H. , Lange P. , Prescott E. 
Published: September 2008

Chronic obstructive pulmonary disease has been associated with a high frequency of arrhythmias. Few studies have analysed the role of reduced lung function in predicting atrial fibrillation (AF). The aim of the present study was to investigate the relationship between forced expiratory volume in one second (FEV1) and risk of first episode of AF in a prospective study.Data from 13,430 males and females without previous myocardial infarction, who participated in the Copenhagen City Heart Study, were analysed. New AF was assessed at re-examination after 5 yrs and by hospital admission for AF during a period of 13 yrs. Multivariate analyses were used with adjustment for cardiopulmonary risk factors. There were 62 new cases of AF at 5-yr follow-up (0.58%) and 290 cases (2.20%) diagnosed at hospitalisations.Risk of new AF at re-examination was 1.8-times higher for FEV1between 60–80% of predicted compared with FEV1≥80% after adjustment for sex, age, smoking, blood pressure, diabetes and body mass index. The risk of AF hospitalisation was 1.3-times higher for FEV1between 60–80% and 1.8-times higher for FEV1<60% compared with FEV1≥80%, when additional adjustment was made for education, treatment with diuretics and chest pain at activity.The authors conclude that reduced lung function is an independent predictor for incident atrial fibrillation.
Procalcitonin as a diagnostic tool in lower respiratory tract infections and tuberculosis
Authors: Polzin A. , Pletz M. , Erbes R. , Raffenberg M. , Mauch H. , Wagner S. , Arndt G. , Lode H. 
Published: September 2008

The diagnostic significance of procalcitonin concentrations in lower respiratory tract infections and tuberculosis is not known. A prospective analysis was, therefore, performed in patients with acute exacerbation of chronic bronchitis (AECB), community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP) and tuberculosis and their procalcitonin levels compared with those of patients with noninfectious lung diseases (controls). In addition, standard inflammatory parameter data were collected.A prospective clinical study was performed with four different groups of patients and a control group that consisted of patients with noninfectious lung diseases. A total of 129 patients were included: 25 with HAP, 26 CAP, 26 AECB, 27 tuberculosis, and 25 controls. C-reactive protein level, blood cell counts and procalcitonin concentration were evaluated on the first day after onset of clinical and inflammatory symptoms prior to treatment.The median procalcitonin concentrations in HAP, CAP, AECB and tuberculosis were not elevated in relation to the cut-off level of 0.5 ng·mL−1. In the HAP group, in four of five patients who subsequently died, procalcitonin concentrations of >0.5 ng·mL−1were found. In acute lower respiratory infections, such as HAP, CAP and AECB, significantly elevated levels were found in comparison to the control group, but below the usual cut-off level. No differences were observed between tuberculosis and the control group.Relative to the current cut-off level of 0.5 ng·mL−1, procalcitonin concentration is not a useful parameter for diagnosis of lower respiratory tract infections. However, compared to the control group, there were significantly elevated levels in patients with hospital-acquired pneumonia, community-acquired pneumonia and acute exacerbation of chronic bronchitis below the current cut-off level, which should be further investigated.
Airway inflammation in waste handlers exposed to bioaerosols assessed by induced sputum
Authors: Heldal K.K. , Halstensen A.S. , Thorn J. , Eduard W. , Halstensen T.S. 
Published: September 2008

Work-associated lower airway inflammation in waste collectors was examined by induced sputum and correlated with the bioaerosol exposure.Organic waste collectors (n=25) underwent induced sputum collection and spirometry before work on Monday and the following Thursday. Total cells, cell differentials, interleukin (IL)-8 and eosinophilic cationic protein were determined. Personal full-shift exposure measurements were performed Monday, Tuesday and Wednesday and analysed for total bacteria, fungal spores, endotoxins and β(1–3)-glucans.The percentage of neutrophils (46–58%) and the IL-8 concentration (1.1–1.4 ng·mL−1) increased from Monday to Thursday. Forced expiratory volume in one second (FEV1) was significantly reduced on Thursday, and the decrease in FEV1/forced vital capacity correlated with the increase in the percentage of neutrophils. The median exposure to endotoxin (range 7–180 EU·m−3) and β(1–3)-glucan (range 5–220 ng·m−3) was correlated with the increase in IL-8.Bioaerosol exposure during waste collection induced an inflammatory response in the lower airways, characterised by neutrophils and interleukin-8 secretion, that influenced the lung function. The inflammatory response was related to microbial components in the bioaerosol and was more pronounced for endotoxin than β(1–3)-glucan exposure. No associations were found for mould spores or bacteria.
Glucocorticoid receptor-binding characteristics in severe asthma
Authors: Bonnans C. , Chanez P. , Meziane H. , Godard P. , Bousquet J. , Vachier I. 
Published: September 2008

The cellular mechanisms associated with severe asthma are still poorly understood. This study investigated the association between glucocorticoid-receptor (GR) alterations and continuous oral glucocorticoid therapy requirement in severe asthma.GR-binding affinity (Kd) and receptor number (n) in peripheral blood monocytes (PBM) obtained from 10 normal subjects, 10 untreated, intermittent asthmatics and 10severe asthmatics were assessed. Moreover, one ability of dexamethasone to inhibit regulated on activation, T-cells expressed and secreted (RANTES) release by these cellsin vitrowas investigated. GR-binding characteristics were studied in PBM using a3H dexamethasone ligand-binding assay and Scatchard analysis. RANTES release was measured in the supernatant of PBM at 24 h using an enzyme-linked immunosorbent assay.No significant differences in Kdand n were found between the three groups of patients. Dexamethasonein vitrowas able to inhibit RANTES release (mean±sem), with the same concentration/response curve in intermittent, untreated asthmatics (0.47±0.22versus1.64±0.31 ng·mL−1) and severe asthmatics (1.49±0.64versus2.59±0.77 ng·mL−1).This study showed that, despite long-term treatment with oral glucocorticoids, there was no evidence of abnormalities in glucocorticoid receptor-binding characteristics in severe asthma, and moreover, it was demonstrated that glucocorticoid receptors were functionalin vitro.
Epidermal growth factor receptor expression in pre-invasive and early invasive bronchial lesions
Authors: Meert A-P. , Verdebout J-M. , Martin B. , Ninane V. , Feoli F. , Sculier J-P. 
Published: September 2008

The 1999 World Health Organization/International Association for the Study of Lung Cancer histological classification of preneoplastic bronchial lesions has been shown to be reproducible but little is known about its biological significance. The current study evaluated the correspondence between the morphological changes of the bronchial epithelium and epidermal growth factor receptor (EGF-R) expression.Thirteen normal bronchial epithelia, 19 hyperplasia, 16 metaplasia, 10 mild dysplasia, one moderate dysplasia, 10 severe dysplasia (SD), 14 carcinomain situ(CIS) and 11 microinvasive tumours were assessed. A global EGF-R score obtained by the sum of the positivity score plus the EGF-R staining intensity score was calculated for each lesion.A global EGF-R score of >5 was reached only in one metaplasia, in six SD, in six CIS and in six microinvasive tumours. There was no difference in EGF-R expression between normal, hyperplastic and metaplastic epitheliaversusmild dysplasia or between severe dysplasiaversusCIS and microinvasive tumours but there was a statistically significant difference between mildversussevere dysplasia.This study demonstrates that epidermal growth factor receptor expression rate changes with the stage of the bronchial lesion, increasing from normal epithelium to carcinomain situand microinvasive tumours with a statistically significant difference between mildversussevere dysplasia.
Minimal important difference of the transition dyspnoea index in a multinational clinical trial
Authors: Witek T.J. , Mahler D.A. 
Published: September 2008

Dyspnoea is a primary symptom of chronic obstructive pulmonary disease (COPD). The baseline (BDI) and transition (TDI) dyspnoea indices are commonly used instruments to assess breathlessness and the impact of intervention. Its validity and pattern of response in multinational clinical trials has not been established.In a retrospective analysis of a cohort of 997 COPD patients who received tiotropium, salmeterol or placebo, in addition to usual care, the validity and pattern of response of the BDI and TDI were examined.The BDI was significantly correlated with the dyspnoea diary (DD) score and the symptom and activity components of the St. George's respiratory questionnaire (SGRQ), establishing concurrent validity. Furthermore, the TDI was also correlated with the changes in DD, SGRQ symptom and activity scores. Construct validity was established by the association between baseline forced expiratory volume in one second (FEV1) and BDI and ΔFEV1with TDI. Physician's global evaluation (PGE) was significantly associated with BDI as well as ΔPGE with TDI. Significant correlations have also been observed when the cohorts were classified according to native English and native non­English speaking countries. A change in PGE of 1 category (i.e.2 units on an 8‐point scale) was associated with a mean TDI of ∼1 unit (0.9–1.3 mean focal score), lending further support to the clinical significance of this change inherent in the instrument's descriptors. TDI responders (i.e.focal score ≥1 unit) used less supplemental salbutamol, had fewer exacerbations and had significantly improved health status as measured by impacts and total SGRQ scores compared with nonresponders.In conclusion, the transition dyspnoea index is a valid instrument when used in a multinational clinical trial and the patterns of response confirm a 1‐unit change in the transition dyspnoea index focal score as being clinically important.
Biological markers in nasal secretions
Authors: Riechelmann H. , Deutschle T. , Friemel E. , Gross H-J. , Bachem M. 
Published: September 2008

Biological markers in nasal secretions provide valuable information on nasal pathophysiology. However, published data on biomarker concentrations in nasal fluids are remarkably inconsistent, and the bias due to different sampling techniques, has not yet been systematically evaluated.Concentrations of various protein were repeatedly determined in nasal secretions of 16 healthy volunteers. The proteins were detected by using: 1) α2-macroglobulin as a marker for plasma contamination; 2) lactoferrin as a marker for glandular secretion; 3) lactate dehydrogenase as a marker for tissue injury; and 4) interleukin (IL)-1β, IL-8, tumour necrosis factor-α, and eosinophil cationic protein and tryptase as indicators for tissue inflammation. A total of four different sampling methods, including nasal lavage (NL) and a new polyurethane foam sampler technique (PFST) were employed.Analyte concentrations in NL were approximately10-times lower than in specimens obtained by PFST. Due to the unpredictable dilution during NL, various analytes were below the detection limit of the high sensitivity assays employed. With PFST, concentrations below the detection limit rarely occurred. The specimens did not significantly differ regarding plasma contamination, glandular secretion or tissue injury.The considerable variability of reported analyte concentrations in nasal secretions mainly results from different sampling techniques. To collect nasal secretions, samplers are considered superior to nasal lavage techniques.
Alveolar macrophages are the main source for tumour necrosis factor‐α in patients with sarcoidosis
Authors: Fehrenbach H. , Zissel G. , Goldmann T. , Tschernig T. , Vollmer E. , Pabst R. , Müller-Quernheim J. 
Published: September 2008

Tumour necrosis factor (TNF)‐α is known to play a major role in the formation of noncaseating granuloma, a hallmark of sarcoidosis. The main cellular sourcein situis still ambiguous.Serial sections of transbronchial biopsies from 14 patients with and 12 without sarcoidosis were studied, using immunohistochemistry (IHC), for TNF‐α, T‐cells (CD3), macrophages (CD68), and epithelial cells (MNF116). TNF‐α spontaneously released (sr-TNF‐α) by freshly isolated bronchoalveolar lavage cells, isolated from the same patients and cultured without any stimulus over a 24‐h period was measured using an enzyme-linked immunosorbent assay.IHC revealed colocalisation of TNF‐α with CD68 cells only. Cases with TNF‐α tissue immunoreactivity exhibited higher sr-TNF‐α (1,667±504 pg·mL−1) than cases without tissue immunoreactivity (211±60 pg·mL−1). In an explorative approach, a subgroup of patients could be identified and characterised by the presence of alveolar macrophage aggregates. It was found that sr-TNF‐α was highest in this subgroup (2,700±769 pg·mL−1) compared with patients with normal histology (221±61 pg·mL−1) or with prominent granuloma (460±137 pg·mL−1), whereas in most clinical parameters this subgroup was intermediate.The findings from this study strongly corroborate the view that alveolar macrophages are the main cellular source for tumour necrosis factor‐α in the initial phase of sarcoidosis. The authors suggest that in these patients, aggregates of alveolar macrophages may represent at least predecessors to granulomas if not granulomasin statu nascendi.
The forced oscillation technique in clinical practice: methodology, recommendations and future developments
Authors: Oostveen E. , MacLeod D. , Lorino H. , Farré R. , Hantos Z. , Desager K. , Marchal F. 
Published: September 2008

The forced oscillation technique (FOT) is a noninvasive method with which to measure respiratory mechanics. FOT employs small-amplitude pressure oscillations superimposed on the normal breathing and therefore has the advantage over conventional lung function techniques that it does not require the performance of respiratory manoeuvres.The present European Respiratory Society Task Force Report describes the basic principle of the technique and gives guidelines for the application and interpretation of FOT as a routine lung function test in the clinical setting, for both adult and paediatric populations.FOT data, especially those measured at the lower frequencies, are sensitive to airway obstruction, but do not discriminate between obstructive and restrictive lung disorders. There is no consensus regarding the sensitivity of FOT for bronchodilation testing in adults. Values of respiratory resistance have proved sensitive to bronchodilation in children, although the reported cutoff levels remain to be confirmed in future studies.Forced oscillation technique is a reliable method in the assessment of bronchial hyperresponsiveness in adults and children. Moreover, in contrast with spirometry where a deep inspiration is needed, forced oscillation technique does not modify the airway smooth muscle tone. Forced oscillation technique has been shown to be as sensitive as spirometry in detecting impairments of lung function due to smoking or exposure to occupational hazards. Together with the minimal requirement for the subject's cooperation, this makes forced oscillation technique an ideal lung function test for epidemiological and field studies. Novel applications of forced oscillation technique in the clinical setting include the monitoring of respiratory mechanics during mechanical ventilation and sleep.
Does interferon‐γ improve pulmonary function in idiopathic pulmonary fibrosis?
Authors: Prasse A. , Müller K-M. , Kurz C. , Hamm H. , Virchow J.C. 
Published: September 2008

Idiopathic pulmonary fibrosis (IPF) is a disease with progressive and devastating deterioration of lung function and a fatal prognosis, despite aggressive therapeutic attempts, which, in the majority of cases are futile.Recently, a preliminary study of long-term treatment with interferon (IFN)‐γ1band low-dose prednisolone in patients with IPF suggested that IFN‐γ1btreatment may improve lung function parameters of patients with IPF. Ever since, specialists in respiratory medicine who treat patients with IPF, are called by patients demanding treatment with IFN‐γ1b. Therefore, the authors here present another prospective investigation of IFN‐γ1bin five patients with IPF.According to the previously published design, patients received 200 µg IFN‐γ1bsubcutaneously three-times per week and 10 mg prednisolone orally for 12 months. Two patients stopped IFN‐γ1btreatment after 4 months due to side-effects and further lung function deterioration and one patient died 3 months after commencement of therapy. In total, pulmonary function improved in only one patient during IFN‐γ1btreatment, while four patients deteriorated.To conclude, this small series of idiopathic pulmonary fibrosis cases treated with interferon‐γ1band corticosteroids does not support previous data that this treatment improves pulmonary function or alters the natural course of idiopathic pulmonary fibrosis. Furthermore, in the authors' experience, side-effects of interferon‐γ1btreatment can significantly reduce patients' quality of life.