bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma TARC concentration may be a useful marker for asthmatic exacerbation in children
Authors: Leung T.F. , Wong C.K. , Lam C.W.K. , Li A.M. , Ip W.K. , Wong G.W.K. , Fok T.F.
Published: September 2008

Recent studies suggested the T-helper cells type-2 lymphocytes-specific thymus and activation-regulated chemokine (TARC) and monocyte-derived chemokine (MDC) are useful inflammatory markers for chronic asthma. However, their roles in assessing the severity of acute asthma are unknown. This study aims to evaluate the serial changes of plasma TARC and MDC concentrations in children with asthmatic exacerbation.

All patients with acute asthma were treated with systemic corticosteroid for 5 days. The severity of asthmatic exacerbation was classified according to the Global Initiative for Asthma guidelines. Plasma TARC and MDC concentrations were measured by sandwich enzyme immunoassays.

Sixteen children, with a median (interquartile range) age of 9.3 (7.2–10.6) yrs and asthmatic exacerbation, were recruited. Plasma TARC concentration showed inverse correlation with peak expiratory flow rate at presentation. The median plasma TARC concentration was highest during the acute attacks (46 pg·mL−1) as compared to those levels at 1 (31 pg·mL−1) and 5 weeks (32 pg·mL−1) following treatment. The median plasma MDC level similarly decreased from 698 pg·mL−1at baseline to 261 pg·mL−11 week later, but increased back to 574 pg·mL−1at 5 weeks.

These results suggest that plasma T-helper cells type-2 lymphocytes-specific thymus and activation-regulated chemokine but not monocyte-derived chemokine concentration may be a useful inflammatory marker in assessing asthmatic exacerbation in children.
Evaluation of airway wall thickness and air trapping by HRCT in asymptomatic asthma
Authors: Gono H. , Fujimoto K. , Kawakami S. , Kubo K.
Published: September 2008

The aim of this study was to examine the relationship between the structural changes in large and small airways in asymptomatic asthmatics quantified by high-resolution computed tomography (HRCT) and airflow obstruction.

The bronchial wall thickness at the trunk of the apical bronchus (B1) of the right upper lobe was used for assessment of the large airways. Air trapping, evaluated by the ratio of the average CT‐determined values for the bilateral upper and lower lung segments at full expiration to that at full inspiration (E/I ratio), was used for assessment of the small airways. Measurements were obtained with a helical HRCT in 24 asymptomatic asthmatics followed by optimal treatment with inhaled and/or oral corticosteroids for >6 months. Prior (20–30 min) to the HRCT examination, all patients were given an inhaled bronchodilator.

The ratio of airway wall thickness to outer diameter (T/D) and the percentage wall area (WA%) at the B1 bronchus and the E/I ratio were significantly greater for the 14 asthmatics with deficient reversible airflow obstruction (forced expiratory volume in one second (FEV1) <80% prediced or FEV1/forced vital capacity <70% after bronchodilator inhalation) than for the 10 asthmatics with normal spirometry and seven normal subjects. T/D, WA%, and E/I ratio showed significant negative correlations with FEV1% pred after bronchodilator inhalation. The E/I ratio also showed significant positive correlations with T/D, WA%, and residual volume/total lung capacity.

These findings suggest that, in spite of optimal treatment, structural changes in both large and small airways may simultaneously occur in asthmatics with deficient reversible airflow obstruction.
Aspirin-sensitive rhinitis-associated changes in upper airway innervation
Authors: Groneberg D.A. , Heppt W. , Welker P. , Peiser C. , Thai Dinh Q. , Cryer A. , Zweng M. , Witt C. , Fischer A.
Published: September 2008

Aspirin-sensitive rhinitis is the manifestation of aspirin intolerance in the upper respiratory tract. The disease represents a pseudoallergy against aspirin or related nonsteroidal anti-inflammatory drugs. As a major immunomodulatory role for airway innervation has been proposed in airway inflammatory diseases, the present study assessed changes in human nasal mucosa innervation in patients with aspirin-sensitive rhinitis in comparison to a control group.

Immunohistochemistry for protein gene product 9.5, tachykinins, calcitonin gene-related peptide, vasoactive intestinal peptide (VIP) and neuropeptide tyrosine was performed on cryostats sections of nasal mucosa and neuropeptide containing nerves were examined independently using a score grading.

In comparison to the control, the aspirin-sensitive rhinitis group had a significant increase of VIP‐like immunoreactivity in mucosal nerve fibres. In contrast to constant numbers of mast cells, highly significant increases in the numbers of eosinophils were found in the group of aspirin-sensitive rhinitis patients.

In summary, the present quantification of neuropeptide-immunoreactivity of mucosal nerves demonstrated differences in the human nasal mucosa innervation between nonrhinitic and aspirin-sensitive rhinitic individuals. These differences may reflect a pathophysiological role of upper airway innervation in pseudoallergic reactions.
Distribution of technetium-99m-labelled QVARTMdelivered using an AutohalerTMdevice in children
Authors: Devadason S.G. , Huang T. , Walker S. , Troedson R. , Le Souëf P.N.
Published: September 2008

QVARTM, an extrafine hydrofluoroalkane/beclomethasone dipropionate formulation, has been shown to double lung deposition in adults. The aim of the present study was to assess the total body deposition and distribution oftechnetium-99m-labelled (99mTc) QVARTMin children after inhalationviaan AutohalerTM.

Sixteen male asthmatic children (5–14 yrs) inhaled labelled drug (<4 MBq99mTc; 100 µg beclomethasone dipropionate)viaan Autohaler within 30 min after salbutamol (200 µg) administration. Simultaneous anterior and posterior planar scintigraphic scans(120 s acquisition time) were collected after inhalation of labelled drug.

Mean±sd lung deposition of labelled drug (attenuation-corrected; percentage of ex-actuator dose) was 36.9±9.2, 46.5±11.6 and 54.1±10.7% in children aged 5–7, 8–10 and 11–14 yrs, respectively. Combined oropharyngeal and gastrointestinal deposition was 59.7±8.2, 48.9±12.3 and 40.3±11.8%. Lung deposition positively correlated with the forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Gastrointestinal dose negatively correlated with the FEV1, FVC, height and age.

In older children (11–14 yrs), lung deposition was almost identical to that reported inadults using QVARTM. In children aged 5–10 yrs, lung deposition using QVARTMwas greater than the levels measured using other commercial aerosol delivery systems. Oropharygeal and gastrointestinal deposition was inversely related toage.
Pulmonary actinomycosis
Authors: Mabeza G.F. , Macfarlane J.
Published: September 2008

Pulmonary actinomycosis is a rare but important and challenging diagnosis to make. Even when the clinical suspicion is high, the disease is commonly confused with other chronic suppurative lung diseases and with malignancy.

An early, accurate diagnosis will prevent the considerable psychological and physical morbidity, including unwarranted surgery, associated with delayed diagnosis.

The clinical, radiological and therapeutic characteristics of the infection are reviewed here.

Respiratory physicians should be aware of this important differential when investigating patients for persistent pulmonary shadowing. This will expedite the diagnosis of an otherwise highly treatable condition with an excellent prognosis if picked up early.
Arginine as an adjuvant to chemotherapy improves clinical outcome in active tuberculosis
Authors: Schön T. , Elias D. , Moges F. , Melese E. , Tessema T. , Stendahl O. , Britton S. , Sundqvist T.
Published: September 2008

Nitric oxide (NO) is involved in the host defence against tuberculosis (TB). Patients with TB exhibit increased catabolism and reduced energy intake. Thus the hypothesis for this study was that restoring a relative deficiency in the amino acid arginine, the substrate for mycobactericidal NO production, would improve the clinical outcome of TB by increasing NO production.

In a randomised double-blind study, patients with smear-positive TB (n=120) were given arginine or placebo for 4 weeks in addition to conventional chemotherapy. Primary outcomes were sputum conversion, weight gain, and clinical symptoms after week 8. Secondary outcomes were sedimentation rate and levels of NO metabolites, arginine, citrulline, and tumour necrosis factor‐α.

Compared with the human immunodeficiency virus (HIV)−/TB+ placebo group, the HIV−/TB+ patients in the arginine group showed significant improvement, defined as increased weight gain, higher sputum conversion rate and faster reduction of symptoms, such as cough. The arginine level increased after week 2 in the HIV−/TB+ arginine group (100.2 µM (range 90.5–109.9)versus142.1 µM (range 114.1–170.1)) compared with the HIV−/TB+ placebo group (105.5 µM (range 93.7–117.3)versus95.7 µM (range 82.4–108.9)). HIV seroprevalence was 52.5%. No clinical improvement or increase in serum arginine was detected in arginine supplemented HIV+/TB+ patients compared with placebo.

Arginine is beneficial as an adjuvant treatment in human immunodeficiency virus-negative patients with active tuberculosis, most likely mediated by increased production of nitric oxide.
Individual and area-based indicators of socioeconomic status and childhood asthma
Authors: Cesaroni G. , Farchi S. , Davoli M. , Forastiere F. , Perucci C.A.
Published: September 2008

The current study evaluated the association between individual and area-based indicators of socioeconomic status and the prevalence, severity, and lifetime hospitalisation for asthma in children.

The representative sample of 4,027 children from Rome, aged 6–7 yrs, used for the 1994 ISAAC (International Study on Asthma and Allergies in Childhood) initiative, was selected. Individual and small area indicators of socioeconomic status were used. Individual data on parents' education and on childhood asthma were gathered from self-administered parental questionnaires. Two small-area indicators (socioeconomic status index (SES) and average income in 1994) were derived using information available at the census tract of residence. Logistic regression models were used to estimate the association of parental education and small area indicators with asthma prevalence, severity, and hospitalisation. Parental smoking was considered in the analysis as a potential confounder.

Prevalence of physician diagnosis of asthma (11.3%) increased as father's education decreased. Prevalence of severe asthma (1.6%) increased as maternal and paternal educational levels decreased. Lifetime hospitalisation for asthma (2.8%) was strongly associated with both parental education and small-area indicators of social disadvantage, even when considered simultaneously in the same logistic model.

Socioeconomic conditions are associated with asthma occurrence, its severity, and hospitalisation. The association was stronger for asthma severity and hospitalisation. Individual indicators correlated better with the outcomes than area-based indicators. However, living in an underprivileged area is a strong independent predictor of hospital admission for asthma.
Climate, traffic-related air pollutants and allergic rhinitis prevalence in middle-school children in Taiwan
Authors: Lee Y-L. , Shaw C-K. , Su H-J. , Lai J-S. , Ko Y-C. , Huang S-L. , Sung F-C. , Guo Y.L.
Published: September 2008

The prevalence of allergic rhinitis, a common respiratory disorder, may be rapidly increasing. Epidemiological studies, however, indicate little about its association with climatic factors and air pollution. The relationship between traffic-related air pollutants and allergic rhinitis in middle-school students was therefore investigated.

In a nationwide survey of middle-school students in Taiwan conducted in 1995/1996, the lifetime prevalence of physician-diagnosed allergic rhinitis and typical symptoms of allergic rhinitis were compared with air-monitoring station data on temperature, relative humidity, sulphur dioxide (SO2), nitrogen oxides (NOx), ozone (O3), carbon monoxide (CO) and particulate matter with a 50% cut-off aerodynamic diameter of 10 µm (PM10).

A total of 331,686 nonsmoking children attended schools located within 2 km of 55 stations. Mean (range) annual exposures were: CO 853 (381–1,610) parts per billion (ppb), NOx 35.1 (10.2–72.4) ppb, SO27.57 (0.88–21.2) ppb, PM1069.2 (40.1–116.2) µg·m−3, O321.3 (12.4–34.1) ppb, temperature 22.9 (19.6–25.1)°C, and relative humidity 76.2 (64.8–86.2)%. The prevalence of physician-diagnosed allergic rhinitis was 28.6 and 19.5% in males and females, respectively, with prevalence of questionnaire-determined allergic rhinitis 42.4 and 34.0%. After adjustment for age, parental education and history of atopic eczema, physician-diagnosed allergic rhinitis was found to be associated with higher nonsummer (September–May) warmth and traffic-related air pollutants, including CO, NOx and O3. Questionnaire-determined allergic rhinitis correlated only with traffic-related air pollutants.

Nonsummer warmth and traffic-related air pollution, probably mediated through exposure to common allergens such as dust mites, are possible risk factors for allergic rhinitis in middle-school-aged children.
Pseudomonas aeruginosaadherence to human basement membrane collagenin vitro
Authors: Tsang K.W. , Shum D.K. , Chan S. , Ng P. , Mak J. , Leung R. , Shum I.H. , Ooi G.C. , Tipoe G.L. , Lam W.K.
Published: September 2008

The mechanisms forPseudomonas aeruginosacolonisation in the airways of patients with bronchiectasis and cystic fibrosis are poorly understood.P. aeruginosacould evade mucociliary clearance by adhering to the basement membrane at areas denuded of intact respiratory epithelium.

The authors have developed anin vitromodel to studyP. aeruginosaadherence tohuman basement membrane type-IV collagen by using scanning electron microscopy.P. aeruginosaadherence density was determined as the number ofP. aeruginosaper 20microscope fields (2,000×) to log inocular size after incubation at 37°C for 45 min.

The presence of phytohaemagglutinin (PHA)-E, which binds specifically to d-galactose-β1–4-d-N-acetylglucosamine, significantly reducedP. aeruginosaadherence density compared with control. The presence of heparin and calcium also significantly reducedP. aeruginosaadherence density.P. aeruginosaadherence was not affected by the presence of proline, trans-hydroxyproline, glycine, galactose,N-acetylneuraminic acid,N-acetylglucosamine orArachis hypogea.

Pseudomonas aeruginosaadherence probably actsviarecognition of the d-galactose-β1–4-d-N-acetylglucosamine sequence on type-IV collagen and this process could be inhibited by heparin and calcium. As persistentPseudomonas aeruginosacolonisation is detrimental to patients with cystic fibrosis and bronchiectasis and there is currently no effective treatment for its eradication, these results could lead to novel therapy for persistentPseudomonas aeruginosainfection.
Respiratory symptoms in children and exposure to pesticides
Authors: Salameh P.R. , Baldi I. , Brochard P. , Raherison C. , Abi Saleh B. , Salamon R.
Published: September 2008

In Lebanon, childhood asthma is an important disease and pesticides are commonly used. The objective of this study was to evaluate whether exposure to pesticides has chronic effects on the respiratory health of Lebanese children.

A cross­sectional study was performed on children from a randomly selected sample of Lebanese public schools. Exposure to pesticides was evaluated by a standardised questionnaire and a residential exposure score, and respiratory symptoms were assessed by using the American Thoracic Society standardised questionnaire.

A chronic respiratory disease was reported in 407 (12.4%) out of 3,291 children. The baseline difference in mean age was small but statistically significant. Any exposure to pesticides, including residential, para­occupational and domestic, was associated with respiratory disease and chronic respiratory symptoms (chronic phlegm, chronic wheezing, ever wheezing), except for chronic cough.

Exposure to pesticides was associated with chronic respiratory symptoms and disease among Lebanese children.
Variation of CD8+ T‐lymphocytes around the bronchial internal perimeter in chronic bronchitis
Authors: Gamble E. , Burns W. , Zhu J. , Ansari T. , De Rose V. , Kips J. , Barnes N.C. , Jeffery P.K.
Published: September 2008

The variation of CD8+ cells has been determined around the internal perimeter of intrapulmonary bronchi in smokers with chronic bronchitis (CB), and the amount of tissue required to confidently estimate the true mean has been calculated.

Lung specimens were obtained from 10 smokers with CB. Paraffin sections of intrapulmonary bronchi were immunostained and CD8+ cells counted in the epithelium and subepithelium in up to 10 sequential 1‐mm segments around the internal perimeter of each airway.

The percentage of counts falling between ±20% of the final mean was 43.0% for epithelium and 40.9% for subepithelium. In 90% of subjects, the cumulative mean was stable after examination of subepithelial tissue associated with 5 mm of reticular basement membrane.

There is considerable variation in the counts of CD8+ cells between adjacent 1‐mm airway mucosal segments in chronic bronchitis. In order to achieve a representative count and to maximise statistical power to detect differences between study populations, subepithelial tissue including a minimum of 5 mm of reticular basement membrane length should be examined.
Combined bronchoalveolar lavage and transbronchial lung biopsy: safety and yield in ventilated patients
Authors: Bulpa P.A. , Dive A.M. , Mertens L. , Delos M.A. , Jamart J. , Evrard P.A. , Gonzalez M.R. , lnstallé E.J.
Published: September 2008

The aim of this study was to evaluate the safety and diagnostic yield of bedside bronchoalveolar lavage (BAL) combined with fibrescopic transbronchial lung biopsy (TBLB) in determining the aetiology of pulmonary infiltrates in mechanically ventilated patients.

The records of 38 mechanically ventilated patients who underwent BAL/TBLB to investigate unexplained pulmonary infiltrates were retrospectively reviewed. Patients were divided into two groups: immunocompetent (group 1: n=22; group 1a: n=11, late acute respiratory distress syndrome (ARDS); group 1b: n=11, no ARDS) and immunocompromised (group 2, n=16).

The procedure allowed a diagnosis in 28 patients (74%), inducing therapeutic modification in 24 (63%) and confirmation of clinical diagnosis in four (11%). In groups 1a, 1b and 2, diagnosis was obtained in 11 out of 11 (fibroproliferation), seven out of 11 and 10 out of 16 patients, and therapy changed in 11 out of 11 (administration of steroids), six out of 11 and seven out of 16 patients, respectively. Pneumothorax occurred in nine patients (four of group 1a), bleeding in four (<35 mL), and transient hypotension in two. No fatalities were procedure-related.

Combined bronchoalveolar lavage/transbronchial lung biopsy is of diagnostic and therapeutic value in mechanically ventilated patients with unexplained pulmonary infiltrates, excluding those with late acute respiratory distress syndrome. Although complications are to be expected, the benefits of the procedure appear to exceed the risks in patients in whom a histological diagnosis is deemed necessary.
The role of mean inspiratory effort on daytime sleepiness
Authors: Pelin Z. , Karadeniz D. , Öztürk L. , Gözükirmizi E. , Kaynak H.
Published: September 2008

This study has investigated the role of average maximum inspiratory effort in excessive daytime sleepiness in patients with obstructive sleep apnoea syndrome (OSAS) and upper airway resistance syndrome (UARS).

Fifteen patients diagnosed with UARS and 32 patients with OSAS, with >5.5 h total sleep time (TST) during 8 h of nocturnal polygraphic recordings, were included in the study. Demographical data, polysomnographical data and data about daytime sleepiness, including Epworth sleepiness scale (ESS) and multiple sleep latency test (MSLT), were evaluated. In order to compute the average maximum inspiratory effort from oesophageal pressure (Poes) measurements, maximumPoeswas obtained from 20 representative obstructive respiratory events (obstructive apnoeas, hypopnoeas or flow limitations) for each sleep stage in both supine and side positions. FromPoesmeasurements during sleep, the increase inPoes(ΔPoes) during respiratory events was also calculated.

The average maximumPoes, ΔPoes, respiratory disturbance index (RDI) and arousal index were significantly correlated with ESS in OSAS patients. In patients with UARS, the only significant correlation was obtained between average maximumPoesand ESS. The MSLT score did not show any significant correlation with arousal index, number of stage variations, RDI, averagePoes, ΔPoes, minimum oxygen saturation (Sa,O2) and percentage of TST with anSa,O2<90% in both UARS and OSAS patients. The results of multiple regression analysis showed that average maximumPoescorrelates best with the variance in ESS for OSAS patients.

In conclusion, the data from this study indicate the possible important role of average inspiratory effort in determining subjective sleepiness in both obstructive sleep apnoea syndrome and upper airway resistance syndrome patients.
Pulmonary disease caused byM. malmoensein HIV negative patients: 5‐yr follow-up of patients receiving standardised treatment
Authors:   The Research Committee of the British Thoracic Society
Published: September 2008

The literature concerning the management of pulmonary disease caused byMycobacterium malmoenseconsists of retrospective reports on small series of patients. A recent multicentre trial conducted by the British Thoracic Society provided an opportunity to prospectively document the clinical features and response to treatment of this relatively rare but challenging disease in a substantial number of patients.

When two positive cultures were confirmed by the Mycobacterium Reference Units for England, Wales, Scotland or Scandinavia, the coordinating physician invited the patient's physician to enrol the patient, who was then treated on a random basis with either rifampicin plus ethambutol or rifampicin, ethambutol and isoniazid for 2 yrs. Clinical, bacteriological and radiological progress were monitored at set intervals for 5 yrs.

In over 5 yrs a total of 106 patients were recruited to the study. The mean age was 58 yrs, range 24–89 yrs. A total of 58% were male and just over half previously or at the time of the study had other lung diseases. Sputum was positive on direct smear in 58%. Cavitation was seen on the chest radiographs of 74%, the majority having cavities of ≥2 cm in diameter. Less than half of the patients showed bilateral disease, 26% having involvement of more than three lung zones. Disease was confined to the upper zone(s) in 30%. Other lung diseases were evident in 52%. Although clinical response was judged satisfactory at most reviews (90%), one in three patients died within 5 yrs and <5% were thought to have died primarily because ofM. malmoense. There were three failures of treatment and eight relapses after the end of treatment. There was no correlation between failure of treatment/relapse andin vitroresistance. A total of 63 (59%) of patients were alive at 5 yrs, of whom 44 (42% of the total entry) were known to be cured.

Pulmonary disease caused byMycobacterium malmoenseis a serious condition that is associated with high morbidity and mortality. The results of standard susceptibility tests do not correlate with the bacteriological response of the disease to chemotherapy. Rifampicin and ethambutol, with or without isoniazid, cured only 42% of patients but were better tolerated than previously described, more complex regimens of equal or lesser efficacy. There is a need for more effective regimens that will reduce mortality and failure of treatment/relapse rates, but, in addition, attention should be directed at improving management of comorbid conditions and improving the general health of the patient.
A role of GM-CSF in the accumulation of neutrophils in the airways caused by IL-17 and TNF‐α
Authors: Laan M. , Prause O. , Miyamoto M. , Sjöstrand M. , Hytönen A.M. , Kaneko T. , Lötvall J. , Lindén A.
Published: September 2008

The T‐cell cytokine interleukin (IL)-17 selectively accumulates neutrophils in murine airwaysin vivoand may thus constitute a link between activation of T‐lymphocytes and accumulation of neutrophils. In this study, the authors evaluated the role of granulocyte macrophage-colony stimulating factor (GM-CSF) in accumulation of neutrophils in the airways caused by IL-17 and tumour necrosis factor (TNF)‐α.

In vitro, human (h) IL-17 concentration-dependently stimulated the release of GM-CSF protein (enzyme-linked immunosorbent assay) in human bronchial epithelial cells (16HBE). IL-17 also time-dependently stimulated the release of GM-CSF protein in venous endothelial (human umbilical vein endothelial cells) cellsin vitro. Co-stimulation with IL-17 plus the pro-inflammatory cytokine TNF‐α potentiated the release of GM-CSF protein in 16HBE cells. hIL-17 also enhanced the expression of GM-CSF messenger ribonucleic acid in 16HBE cells (reverse transcriptase polymerase chain reaction), with a similar order of magnitude as TNF‐α. Conditioned cell medium from bronchial epithelial cells co-stimulated with hIL-17 plus TNF‐α prolonged survival (trypan blue exclusion) of human neutrophilsin vitroand this effect was blocked by an anti-GM-CSF antibody.In vivo, local co-stimulation with mouse IL-17 plus TNF‐α caused an additive potentiation of the accumulation of neutrophils in bronchoalveolar lavage fluid from mouse airways and this effect was blocked by an anti‐GM-CSF antibody given systemically.

In conclusion, granulocyte macrophage-colony stimulating factor is involved in the accumulation of neutrophils in the airways caused by interleukin-17 and tumour necrosis factor‐α, probablyviaeffects on both recruitment and survival of neutrophils.
Bronchial asthma causing symptoms suggestive of angina pectoris
Authors: Kiss D. , Veegh W. , Schragel D. , Bachl C. , Stöllberger C. , Sertl K.
Published: September 2008

Many patients undergoing pharmacological stress echocardiography for assessing symptoms suggestive of coronary artery disease are found to have a normal test. This study was performed to evaluate whether asthma symptoms simulate angina pectoris.

A total 41 consecutive patients who had a negative pharmacological stress echocardiography and had been evaluated for angina pectoris were studied. Patients with previously known coronary artery disease or obstructive lung disease were excluded. Lung function testing was performed and the authors proceeded either with the administration of a bronchodilator or with methacholine challenge testing. A questionnaire was applied to assess the symptoms dyspnoea, chest tightness and substernal burning at the end of the challenge test. In addition, patients were asked if they were experiencing those symptoms that made them seek medical attention. From the 41 patients tested, 26 patients showed a significant bronchial hyperreactivity (mean±sd provocative concentration causing a 20% fall in the forced expiratory volume in one second 5.93±4.50 mg·mL−1). A total of 20 patients confirmed having those symptoms that led to cardiac evaluation.

It was concluded that symptoms suggestive of angina pectoris might represent bronchial asthma. This should be considered in the differential diagnosis of angina pectoris.
Inhaled corticosteroids and growth of airway function in asthmatic children
Authors: Merkus P.J.F.M. , van Pelt W. , van Houwelingen J.C. , van Essen-Zandvliet L.E.M. , Duiverman E.J. , Kerrebijn K.F. , Quanjer P.H.
Published: September 2008

Airway inflammation and remodelling play an important role in the pathophysiology of asthma. Remodelling may affect childhood lung function, and this process may be reversed by anti-inflammatory treatment. The current study assessed longitudinally whether asthma affects growth of airway function relative to airspaces, and if so whether this is redressed by inhaled corticosteroids (ICS).

Every 4 months for up to 3 yrs, lung function was assessed in 54 asthmatic children (initial age 7–16 yrs), who inhaled 0.2 mg salbutamolt.i.d.and 0.2 mg budesonidet.i.d.(β2‐agonist (BA)+ICS), or placebo (PL)t.i.d. (BA+PL) in a randomised, double-blind design. Measurements were carried out before and after maximal bronchodilation. Airway growth was assessed from the change of forced expiratory volume in one second and of maximal expiratory flows (at 60% and 40% of total lung capacity (TLC) remaining in the lung) relative to TLC, as measures of more central, intermediate and more peripheral airways. Growth patterns were compared with the longitudinal findings in 376 healthy children.

Airway patency after maximal bronchodilation in patients on BA+PL remained reduced compared to healthy subjects, whereas in patients on BA+ICS a marked improvement was observed to subnormal. No differences between patients and controls could be demonstrated for growth patterns of central and intermediate airway function. Compliance with BA+ICS was 75% of the prescribed dose, resulting in significant, sustained improvement of symptoms and postbronchodilator calibre of central and intermediate airways to subnormal within 2 months, but postbronchodilator small airway patency remained reduced, though improved compared to patients on BA+PL.

Anti-inflammatory treatment of asthmatic children is associated with normal functional development of central and intermediate airways. The persistently reduced postbronchodilator patency of peripheral airways may reflect remodelling, or insufficient anti-inflammatory treatment.
Effect of saliva contamination on induced sputum cell counts, IL‐8 and eosinophil cationic protein levels
Authors: Simpson J.L. , Timmins N.L. , Fakes K. , Talbot P.I. , Gibson P.G.
Published: September 2008

Excessive salivary contamination of induced sputum samples prevents the satisfactory examination of lower airway inflammation. The effects of salivary contamination on different sputum fluid phase measures and the levels of salivary contamination preventing analysis are not defined. The present study sought to examine this by investigating the effect of increasing salivary contamination on induced sputum samples.

Sputum and saliva samples from subjects with asthma and healthy controls were collected, and treated with dithiothreitol (DTT). Saliva was then added to aliquots of dispersed sputum in increasing proportions (0% to 100%). The effect of increasing saliva contamination was assessed on sputum total cell count, viability, differential cell count and fluid phase levels of interleukin (IL)‐8, eosinophil cationic protein (ECP) and total protein.

The addition of saliva to induced sputum reduced total cell counts and absolute cell counts but did not change the differential cell count. Levels of fluid phase ECP and IL‐8 were significantly reduced with increased salivary contamination. There was a progressive reduction in ECP and IL‐8, which reached significance at 70% and 80% saliva contamination, respectively. IL‐8 levels corrected for total protein showed no change with increasing saliva concentrations.

Induced sputum differential cell counts expressed as the proportion of nonsquamous cells are robust measures that are not influenced by salivary contamination. Studies reporting total and absolute cell counts and fluid phase mediator levels require control for squamous contamination.
Prenatal nicotine exposure increases connective tissue expression in foetal monkey pulmonary vessels
Authors: Sekhon H.S. , Proskocil B.J. , Clark J.A. , Spindel E.R.
Published: September 2008

Among the many deleterious effects of maternal smoking during pregnancy on foetal development, is a higher incidence of persistent pulmonary hypertension. The recent identification of nicotinic acetylcholine receptors (nAChR) on cells of the pulmonary vessel walls suggests that maternal smoking during pregnancy may produce morphological alterations in foetal pulmonary vasculature.

Timed­pregnant rhesus monkeys were treated with nicotine (1 mg·kg−1·day−1) delivered by subcutaneous osmotic mini­pumps from days 26–134 of gestation (term: 165 days). Lung sections from 134‐day foetal monkeys were used for morphometric analysis,in situhybridisation and immunohistochemical staining.

Following nicotine treatment, total wall and tunica adventitia thickness of airway associated vessels (AAV) increased significantly. Nicotine exposure significantly increased collagen I and III mRNA and protein in tunica adventitia in all AAV but not in tunica media. By contrast, levels of elastin protein were significantly decreased. α7 nAChR were detected in AAV fibroblasts that expressed collagen mRNA. Choline acetyltransferase, the enzyme which synthesises acetylcholine, the ligand for α7 nAChR was also detected in endothelium and fibroblasts.

These findings suggest that with smoking during pregnancy, nicotine is transported across the placenta and directly interacts with nicotinic acetylcholine receptors in pulmonary vessels to alter connective tissue expression and therefore produce vascular structural alterations.
Effect of inhaled steroids on lung function in young children: a cohort study
Authors: Devulapalli C.S. , Haaland G. , Pettersen M. , Carlsen K.H. , Lødrup Carlsen K.C.
Published: September 2008

The objectives of the present study were to determine the use of inhaled corticosteroids (ICS) for treating recurrent bronchial obstruction (rBO) in young children up to 2 yrs of age and to assess possible modifying effects of ICS on lung function in young children with rBO. From an observational, noninterventional birth cohort of 3,754 newborn children (3,697 with complete questionnaire data by 2 yrs of age), 306 children with documented rBO by age 2 yrs (cases) were identified along with 306 matched controls.

Two tidal flow/volume measurements were taken, one at presentation of disease (children were steroid naïve) and one at 2 yrs of age (mean age 11.2 and 25.6 months, respectively), from: 21 cases who subsequently received ICS (ICS+); 33 who did not (ICS−); and in 15 controls. The mean±sd duration of ICS treatment was 10.3±6.5 months. The main outcomes were treatment with ICS and baseline ratio of time to peak expiratory flow/total expiratory time (tPTEF/tE).

From the entire cohort, 77 children (2.1%) and 21% of children with rBO had received ICS by 2 yrs of age. BaselinetPTEF/tEwas significantly lower at the first visit only in ICS+ as compared to ICS− subjects, as well as in ICS+ and ICS- as compared to controls. The mean difference in baselinetPTEF/tEfrom first to second visit was borderline statistically significant in the ICS+ group only and correlated significantly with duration of ICS treatment.

The present observational cohort study demonstrated that one-fifth of young children with recurrent bronchial obstruction had received inhaled corticosteroids. Early inhaled corticosteroid treatment improved lung function by age 2 yrs, mostly in those with the longest duration of treatment.
Expression of HCLCA1 in cystic fibrosis lungs is associated with mucus overproduction
Authors: Hauber H.P. , Tsicopoulos A. , Wallaert B. , Griffin S. , McElvaney N.G. , Daigneault P. , Mueller Z. , Olivenstein R. , Holroyd K.J. , Levitt R.C. , Hamid Q.
Published: September 2008

Mucus overproduction is typical in cystic fibrosis (CF) airway disease. The human calcium-activated chloride channel, hCLCA1, has been reported to be upregulated by interleukin (IL)‐9 and to regulate the expression of mucins. Therefore, the expression of IL‐9, IL‐9 receptor (IL‐9R) and hCLCA1 between the lungs of CF patients and healthy control subjects was compared.

Endoscopic biopsy samples of bronchial mucosa from 10 CF patients and six control subjects were stained with periodic acid-Schiff. IL‐9, IL‐9R and hCLCA1 expression was determined by immunocytochemistry. Expression of hCLCA1 mRNA was also determined byin situhybridisation.

The present study found significant increases in IL‐9, IL‐9R and hCLCA1 immunoreactivity, hCLCA1 mRNA expression, and numbers of mucus-producing cells in the mucosa of CF patients compared to control subjects. Positive correlations were found between IL‐9R‐positive-cells with IL‐9‐positive cells and hCLCA1-positive cells, and between PAS-positive cells with hCLCA1-positive cells and IL‐9R‐positive cells. Expression of hCLCA1 mRNA was colocalised with IL‐9R expression and PAS-positive staining in epithelial cells.

Increased expression of interleukin‐9 and interleukin‐9 receptor, as well as an upregulation of the human calcium-activated chloride channel, hCLCA1, in mucus-producing epithelium of cystic fibrosis patients, support the hypothesis that interleukin‐9 contributes to mucus overproduction in cystic fibrosis airway disease.
A case of steroid responsive pulmonary hyalinising granuloma: complicated by deep venous thrombosis
Authors: O'Reilly K.M.A. , Boscia J.A. , Kaplan K.L. , Sime P.J.
Published: September 2008

A case of pulmonary hyalinising granuloma (PHG) complicated by deep venous thrombosis (DVT) is presented.

The DVT was associated with the presence of a lupus anticoagulant. In the past PHG has been linked to various auto-antibodies, but to the best of the authors' knowledge, this is the first case reporting PHG in association with a lupus anticoagulant and clinically significant venous thrombosis. Historically, PHG has been regarded as poorly corticosteroid responsive. However, the patient in this case study responded dramatically to prednisone.

This case study suggests that in selected patients with pulmonary hyalinising granuloma experiencing disabling symptoms and worsening pulmonary function, a trial of corticosteroids may be warranted.
Effect of smoking on MAP kinase-induced modulation of IL‐8 in human alveolar macrophages
Authors: Koch A. , Giembycz M. , Stirling R.G. , Lim S. , Adcock I. , Waßermann K. , Erdmann E. , Chung K.F.
Published: September 2008

Inflammatory cytokine production by alveolar macrophages (AMs) is regulated by transcriptional activation and may be increased by cigarette smoking.

The smoking-induced regulation of interleukin (IL)‐8 by extracellular signal-regulated kinase (ERK)‐1 and ‐2, p38 mitogen-activated protein kinase (MAPK) and the transcription factor nuclear factor‐κB (NF‐κB) in lipopolysaccharide-stimulated AMs was assessed in nine smokers compared with nine healthy nonsmokers.

IL‐8 production was dependent on phosphorylation of ERK‐1 and ‐2 and p38 MAPK, as examined by PD 098059 (10 µM), an inhibitor of the upstream activator of MAPK kinase (MKK)‐1, and SB 203580 (10 µM), an inhibitor of p38 MAPK. IL‐8 release and the inhibitory effect of PD 098059 were increased in AMs from smokers. Moreover, ERK‐2 messenger ribonucleic acid expression, as examined by reverse transcriptase polymerase chain reaction and phosphorylation of ERK‐2 using Western blots, were increased in AMs from smokers, indicating a smoking-induced modulatory role of ERK‐1 and ‐2. Lipopolysaccharide-induced IL‐8 production was dependent on activation of NF‐κB, as examined by SN 50 (100 µM), an inhibitor of NF‐κB translocation, and the specific NF‐κB inhibitor kinase‐2 inhibitor, AS 602868 (10 µM), with no differences in AMs from smokers and nonsmokers. SN 50 but not PD 098059 and SB 203580 blocked NF‐κB deoxyribonucleic acid-binding, and this occurred to the same extent in AMs from smokers and nonsmokers, as examined by electromobility shift assay.

It is concluded that cigarette smoking enhances mitogen-activated protein kinase activation more than nuclear factor‐κB activation to increase lipopolysaccharide-induced interleukin‐8 production in alveolar macrophages.
Genetic polymorphism of epoxide hydrolase and glutathione S-transferase in COPD
Authors: Cheng S‐L. , Yu C‐J. , Chen C‐J. , Yang P‐C.
Published: September 2008

Genetic susceptibility to the development of chronic obstructive pulmonary disease (COPD) might depend on variation in the activities of enzymes that detoxify cigarette smoke products, such as microsomal epoxide hydrolase (mEPHX) and glutathioneS-transferase (GST). It was investigated whether polymorphisms in these genes had any association with susceptibility to COPD and COPD severity.

The genotypes of 184 patients with COPD and 212 control subjects were determined by polymerase chain reaction followed by restriction fragment length polymorphism analysis of the mEPHX, GSTM1, GSTT1 and GSTP1 genes. All subjects were smokers or exsmokers.

The proportion of GSTM1-null genotypes was significantly higher in patients with COPD than in control subjects (61.4versus42.5%). No differences were observed in the frequency of polymorphic genotypes for mEPHX, GSTT1 and GSTP1. During combined analysis of genetic polymorphisms for mEPHX, GSTM1 and GSTP1, it was found that there are strong indicators for susceptibility to COPD (genotype combination with at least one mutant mEPHX exon‐3 allele (histidine 113), GSTM1 null and homozygous for the GSTP1 isoleucine 105 allele). The frequencies of homozygous mutant alleles of mEPHX exon 3 and the GSTM1-null genotype were significantly higher in patients with severe COPD (forced expiratory volume in one second of <35% of the predicted value).

It is proposed that the combination of genetic variants including at least one mutant microsomal epoxide hydrolase exon‐3 allele and glutathioneS-transferase M1-null and homozygous isoleucine 105 glutathioneS-transferase P1 genotypes are significant indicators of susceptibility to chronic obstructive pulmonary disease in the Taiwanese population. In addition, the homozygous variant of microsomal epoxide hydrolase exon 3 and the glutathioneS-transferase M1-null genotype are independent risk factors for developing severe chronic obstructive pulmonary disease.
Prevention of MRSA pneumonia by oral vancomycin decontamination: a randomised trial
Authors: Silvestri L. , van Saene H.K.F. , Milanese M. , Fontana F. , Gregori D. , Oblach L. , Piacente N. , Blazic M.
Published: September 2008

This study was undertaken to assess whether oropharyngeal vancomycin may control oropharyngeal carriage and lower airway infection due to methicillin‐resistantStaphylococcus aureus(MRSA) acquired in the intensive care unit (ICU). Secondary endpoints were the emergence of vancomycin-resistant enterococci, vancomycin-intermediateS. aureusand vancomycin consumption.

A total of 84 patients, admitted to a medical/surgical ICU and mechanically ventilated for >72 h, were randomly assigned to control (n=42) or test (n=42) group. Both groups received the protocol of selective decontamination of the digestive tract, including polymyxin E, tobramycin and amphotericin B. Patients in the test group received 0.5 g of a 4% vancomycin gel at 6‐h intervals in the oropharynx.

Lower airway infections due to MRSA acquired on the ICU were reduced in the test group, as was oropharyngeal carriage. Neither vancomycin-resistant enterococci nor vancomycin-intermediateS. aureuswere isolated from either surveillance or diagnostic samples during the study period. The vancomycin costs were lower in the test group.

This study demonstrates that oropharyngeal vancomycin, which controls intensive care unit‐acquired lower airway infections and secondary carriage due to methicillin-resistantStaphylococcus aureus, is cost-effective and safe in terms of vancomycin-resistant enterococci and vancomycin-intermediateStaphylococcus aureus.
Epidemiology ofBurkholderia cepaciacomplex colonisation in cystic fibrosis patients
Authors: De Boeck K. , Malfroot A. , Van Schil L. , Lebecque P. , Knoop C. , Govan J.R.W. , Doherty C. , Laevens S. , Vandamme P.
Published: September 2008

In Belgian cystic fibrosis (CF) clinics, sputum samples are evaluated on selective MAST medium routinely every 3 months. In this study, in 1993 and 1999, isolates were further examined byrecArestriction fragment length polymorphism analysis and pulsed-field gel electrophoresis of genomic DNA restricted withSpeI.

In 1993, 12 patients were colonised withBurkholderia cepaciacomplex (Bcc):B. cenocepacia(n=6),B. multivorans(n=3),B. stabilis(n=3). Four patients were colonised with the sameB. cenocepaciastrain; two with the sameB. stabilisstrain. After 5 yrs, threeB. cenocepacia- and oneB. multivorans-colonised patients had died.

In 1999, Bcc was isolated in 12 patients:B. multivorans(n=9),B. stabilis(n=1) andB. cenocepacia(n=2). Three patients were colonised by the sameB. multivoransstrain. Compared to matched controls, the 5 yr outcome was poor; fourB. cepaciapatients died and none of the control patients died. Lung-function evolution was poor.

In conclusion, the rate of colonisation in Belgian cystic fibrosis patients is stable and low.Burkholderia cenocepaciawas most prevalent in 1993;Burkholderia multivoransin 1999. The cross-infection rate is low. Three patients had transient colonisation. The impact ofBurkholderia cepaciacomplex on morbidity in the Belgian cystic fibrosis population is high and not limited toBurkholderia cenocepacia.
End points in pulmonary arterial hypertension: the way forward
Authors: Peacock A. , Naeije R. , Galié N. , Reeves J.T.
Published: September 2008

Pulmonary arterial hypertension is a rare disease of poor prognosis.

Despite its rarity >1,000 patients have been randomised in placebo-controlled trials using novel therapies, including prostacyclin analogues, endothelin receptor antagonists and, most recently, phosphodiesterase 5 inhibitors. Nearly all of these trials have used exercise capacity, measured by the unencouraged 6‐min walking distance, as the primary end point and a variety of other measurements as secondary end points. This approach has been productive, leading to the licensing of a number of effective treatments. Future clinical trials, however, will probably assess drug combinations, make comparisons between drugs and include less severely ill patients. It is, therefore, timely to examine the end points used.

The authors discussed the various end points that have been used in the past and possible end points that might be used in the future. End points considered included measurements of: exercise capacity, haemodynamics, quality of life, imaging of the right heart and circulation, and chemical markers of pulmonary hypertension.

Many of these show promise but will have to be used in parallel and compared with conventional end points such as the 6‐min walking distance before their value can be demonstrated convincingly to the regulatory authorities.