bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiomer® reduces the chemokine interleukin-;8 production by activated human respiratory epithelial cells
Authors: Tabary O. , Muselet C. , Yvin J-;C. , Halley-Vanhove B. , Puchelle E. , Jacquot J.
Published: July 2002

The authors have recently shown that the transcription factor nuclear factor-κB (NF-κB) is a central mediator in the NaCl-mediated interleukin (IL)-;8 production by human airway epithelial cells. In this study, it was investigated whether Physiomer®, an isotonic sea water-derived solution commercialized for cleaning the nasal mucosa, impaired the chemokine IL-;8 expression and secretion by human respiratory epithelial cells compared with that obtained with an isotonic 9% NaCl solution.

Primary human bronchial gland (HBG) epithelial cells were incubated either in Physiomer® or in a NaCl 9% solution and activated either with 20 ng·mL−1tumour necrosis factor-;α, or IL-;1β, respectively. Physiomer® significantly reduced the IL-;8 protein release in basal and activated HBG cells in comparison with that obtained with the 9% NaCl solution. In contrast to the effects of Physiomer® observed on resting HBG cells, Physiomer® did not significantly reduce the level of phosphorylation of the NF-κB inhibitor protein IκBα or the steady-state IL-;8 messenger ribonucleic acid levels in activated HBG cells, suggesting that Physiomer® would have a post-transcriptional effect on IL-;8 expression in activated HBG cells.

The authors conclude that Physiomer® is potentially useful in the reduction of airway mucosal inflammation.
Unaltered perception of dyspnoea during treatment with long-acting β2-agonists
Authors: van der Woude H.J. , Aalbers R.
Published: July 2002

There is the possibility that during treatment with inhaled long-acting β2-agonists that a loss of perception of dyspnoea might occur and that the forced expiratory volume in one second (FEV1) might fall precipitously during bronchial provocation. This study investigated these possibilities during methacholine provocation, continued until there was ≥30% fall in FEV1, mimicking a moderate asthma attack.

Nineteen asthmatic patients were asked to score their dyspnoea as a Borg score during provocation with methacholine. One hour prior to this provocation, the patients used the last morning dose of 14 days treatment with either formoterol (twice daily 24 µg by Turbuhaler®), salmeterol (twice daily 100 µg by DiskhalerTM) and placebo in a double-blind, randomized, double-dummy, cross-over design.

The perception of dyspnoea, expressed as the Borg score divided by the change in FEV1at ≥30% fall in FEV1, was similar on the three test days at 0.067, 0.076 and 0.074%−1after formoterol, salmeterol and placebo treatment, respectively (p=0.16). The slope of the methacholine dose response curve did not differ (p=0.52).

In conclusion, no suggestion was found for an abnormal perception of dyspnoea or an exaggerated fall in forced expiratory volume in one second during provocation with methacholine under long-acting β2-agonist treatment.
Computed tomography of pulmonary sarcoid-like granulomas induced by complete Freund's adjuvant in rats
Authors: Bergeron A. , Laissy J-P. , Loiseau P. , Schouman-Claeys E. , Hance A.J. , Tazi A.
Published: July 2002

Intravenous injection of complete Freund's adjuvant (CFA) in rats has been proposed as an experimental model for pulmonary sarcoidosis, but only some animals develop granulomas. Because the detection of the presence of granulomas and evaluation of the extent of the reaction has required histological evaluation, this model has been of limited use in following the evolution of the granulomatous process.

The present study evaluated the ability of lung computed tomography (CT) scanning to identifyin vivopulmonary granulomas induced by CFA in rats. Wistar rats were injected with CFA to induce pulmonary sarcoid-like granulomas, and the presence and extent of pulmonary abnormalities, as detected by spiral CT and histopathological analysis, were compared.

Spiral CT had a high sensitivity and specificity for the detection of sarcoid-like granulomas in rats injected with CFA. The extent of the pulmonary granulomatous reaction as assessed by the two techniques strongly correlated (r=0.93, p<0.01). In contrast, the mean density of lungs containing granulomas was not significantly different from that of lungs with no granulomatous reaction.

Thus, lung computed tomography appears to be a valuable tool for thein vivoevaluation of the pulmonary granulomatous reaction induced by complete Freund's adjuvant in rats. With the help of computed tomography, this experimental model should be suitable for the sequential study of pulmonary sarcoid-like granulomas, particularly in response to various therapeutic strategies.
The tuberculin skin test in relation to immunologicalin vitroreactions in BCG-vaccinated healthcare workers
Authors: Fjällbrant H. , Ridell M. , Larsson L.O.
Published: July 2002

The aim was to study the tuberculin skin test in relation to immunologicalin vitroreactions in bacille Calmette-Guérin (BCG)-vaccinated healthcare workers.

The present study was performed in Sweden, a country with a low incidence of tuberculosis, a high BCG vaccination efficacy and high tuberculin conversion rates. BCG-vaccinated healthcare workers (n=381) were tuberculin skin tested. From these, 11 subjects with negative tuberculin reactions (<6 mm) were matched for age and sex with 11 subjects with large positive reactions (≥15 mm). Lymphocyte transformation and the production of interferon-gamma (IFN-γ) were analysed after stimulationin vitroof peripheral blood mononuclear cells with tuberculin purified protein derivative, heat-killed tubercle bacilli and a culture filtrate from tubercle bacilli.

In the tuberculin-positive group the lymphocyte transformation response was 2–3 times larger, and IFN-γ production was 7–10 times larger, than in the tuberculin-negative group (p<0.001).

The present results suggest that a positive tuberculin skin test in bacille Calmette-Guérin-vaccinated subjects indicates a stronger immune response of the protective T-helper 1-type than does a negative test. In similar settings, the study supports the traditional practice of regarding the tuberculin skin test in bacille Calmette-Guérin-vaccinated subjects as an indicator of a protective immune response against tuberculosis.
The effects of coronavirus on human nasal ciliated respiratory epithelium
Authors: Chilvers M.A. , McKean M. , Rutman A. , Myint B.S. , Silverman M. , O'Callaghan C.
Published: July 2002

Human coronavirus (HCoV) accounts for 15–30% of common colds, but only one case report has described the effect of a coronavirus infection, that was asymptomatic, on human respiratory epithelium.

The authors examined the effects of infection with HCoV on ciliary structure and function in healthy volunteers infected by intranasal inoculation with HCoV 229E. A further four volunteers were sham infected with ultraviolet-inactivated virus. Immediately before inoculation (day 0) and 3 days later (day 3), ciliated epithelium was obtained by brushing the inferior nasal turbinate. Ciliary beat frequency was determined and beat pattern analysed for evidence of dyskinesia (0=normal, 3=severely dyskinetic) using digital high-speed video photography. Ciliary ultrastructure was examined by transmission electron microscopy. Symptom diaries were kept for the duration of the study.

All subjects inoculated with HCoV, including the three who did not develop symptoms of an upper respiratory tract infection, had disruption of their respiratory epithelium on day 3. Although there was no difference in the mean ciliary beat frequency between day 0 (11.3 Hz (95% confidence interval (CI): 8.6–14.0) and day 3 (9.4 Hz (95% CI 7.2–11.6)), there was a significant increase (p<0.05) in the ciliary dyskinesia score between day 0 (0.2 (95% CI 0–0.5)) and day 3 (1.1 (95% CI 0.5–1.7). In sham-infected subjects, no differences in epithelial integrity, or ciliary structure and function were found between day 0 and day 3.

Inoculation of healthy volunteers with human coronavirus caused disruption of the ciliated epithelium and ciliary dyskinesia. This is likely to impair mucociliary clearance. Damage to the respiratory epithelium, due to human coronavirus infection, may occur without overt clinical symptoms.
Increased detection of interleukin-;5 in sputum by addition of protease inhibitors
Authors: Kelly M.M. , Leigh R. , Carruthers S. , Horsewood P. , Gleich G.J. , Hargreave F.E. , Cox G.
Published: July 2002

The measurement of interleukin (IL)-;5 in sputum is problematic, with interfering factors affecting immunoassay. The authors investigated whether sputum proteases could be acting as interfering factors by studying the effect of protease inhibitors (PI) on sputum IL-;5 measurement.

Induced sputa from 20 subjects with asthma were divided into aliquots, processed with and without protease inhibitors (in low and high concentrations) and the levels of IL-;5 (spiked and endogenous) measured by enzyme immunoassay were compared.

The concentration of sputum IL-;5 was significantly increased by PI, with median (interquartile range) levels processed with no, low and high PI concentrations being 0 (0), 41.8 (75.6) and 66.1 (124.4) pg·mL−1, respectively. There was also a significant increase in percentage recovery of spiked IL-;5. Although high concentrations of PI reduced cell viability, there was no effect on total or differential cell counts and low concentrations of PI had no effect on cell counts or viability.

Levels of endogenous interleukin-;5 in sputum of asthmatic subjects can be significantly increased by the addition of protease inhibitors, and samples which would be regarded as negative for interleukin-;5 without protease inhibitors may instead have considerable amounts of interleukin-;5 detected.
The humoral immune response to influenza vaccination in lung transplant patients
Authors: Mazzone P.J. , Mossad S.B. , Mawhorter S.D. , Mehta A.C. , Schilz R.J. , Maurer J.R.
Published: July 2002

The purpose of this study was to evaluate the humoral immune response to influenza vaccination in lung transplant recipients.

Antibody levels to the three viral antigens included in the 1999–2000 trivalent influenza vaccine (A/Sydney/5/97-like (H3N2), A/Beijing262/95-like (H1N1), and B/Yamanashi/16/98) were measured before and 4 weeks postvaccination in 43 lung transplant recipients and 21 healthy adult controls. The ability to develop protective antibody levels, a serological response, and the magnitude of change in levels were assessed.

The humoral immune response to influenza vaccination was significantly lower in the transplant group for all three viral antigens. To A/Sydney, 95% of the control group and 40% of the transplant group developed protective levels (p=0.0009); to A/Beijing, 71% of the control group and 30% of the transplant group developed protective levels (p=0.004); and to B/Yamanashi, 48% of the control group and 19% of the transplant group developed protective levels (p=0.02). Those receiving cyclosporine had lower antibody responses when compared to those receiving tacrolimus (r=−0.3056, p=0.0463).

The humoral immune response to influenza vaccination in lung transplant recipients is poor. Lung transplant recipients receiving cyclosporine may have a lower antibody response than those receiving tacrolimus. Alternative prevention strategies may be needed.
Evaluation of bronchodilator responses in patients with “irreversible” emphysema
Authors: O'Donnell D.E. , Forkert L. , Webb K.A.
Published: July 2002

Given the emerging physiological and clinical rationale for pharmacological lung-volume reduction, assessment of volume responses to bronchodilators is likely to be highly relevant in chronic obstructive pulmonary disease (COPD). The authors examined the magnitude of lung-volume reduction after acute bronchodilator treatment in patients with advanced emphysema.

Eighty-four stable patients with emphysema (mean±sem forced expiratory volume in one second (FEV1): 32±1% predicted) performed spirometry and body plethysmography before and 15–30 min after 200 µg salbutamol. Only irreversible patients with a postbronchodilator change in FEV1<10% pred were considered in this study.

Postsalbutamol, the majority of subjects (83%) had significant improvements in one or more lung volumes: on average, residual volume (RV), functional residual capacity (FRC), inspiratory capacity (IC), forced vital capacity and slow vital capacity changed by −18±2, −10±1, 8±1, 9±1 and 7±1% pred (p<0.0005 each). Total lung capacity (TLC) decreased 0.12±0.04 L (p<0.01). Change in IC reflected change in FRC (r=−0.60, p<0.0005), but more strongly in the 57% of patients with no significant change in TLC (r=−0.93, p<0.0005). The magnitude and frequency of volume responses were greatest in patients with the most severe COPD; for example, RV decreased by 0.51±0.09 L (23±4% pred) and 0.27±0.04 L (14±2% pred) in severe and moderate subgroups, respectively.

Significant reductions in lung hyperinflation occurred in the absence of a change in forced expiratory volume in one second after low-dose salbutamol in a majority of patients with advanced emphysema; the greatest changes occurred in those with the most severe disease.
The immunology of virus infection in asthma
Authors: Message S.D. , Johnston S.L.
Published: July 2002

The respiratory tract is commonly infected by a range of viruses with overlapping pathologies. The majority of episodic exacerbations of asthma are associated with viral infection, in particular with rhinovirus infections.

Experimental rhinovirus infection in human volunteers provides a useful model of natural virus-induced asthma. The asthmatic airway is characterized by an infiltrate of eosinophils and T-lymphocytes expressing the type 2 cytokines interleukin (IL)-4, IL-5 and IL-13. An effective antiviral immune response requires early viral clearance and appropriate termination of the immune response to minimize associated immunopathology and tissue damage.

The antiviral immune response is made up of innate (nonspecific) and specific components, and requires the coordinated actions of many different cell types including neutrophils, macrophages, eosinophils, dendritic cells, epithelial cells, mast cells, natural killer cells and B- and T-lymphocytes. Coordination of this response involves numerous cytokines and chemokines. T-lymphocytes expressing type 1 cytokines including interferon-γ play a key role.

Pre-existing asthmatic inflammation in the lower airway may modify the immune response to viral infection by altering the balance of T-cell cytokine expression from type 1 towards a type 2 in what is always a mixed response. The consequence is delayed viral clearance, persistent virus-induced inflammation and amplification of the allergic inflammation.
Lung mucosal immunity: immunoglobulin-A revisited
Authors: Pilette C. , Ouadrhiri Y. , Godding V. , Vaerman J-P. , Sibille Y.
Published: July 2002

Mucosal defence mechanisms are critical in preventing colonization of the respiratory tract by pathogens and penetration of antigens through the epithelial barrier. Recent research has now illustrated the active contribution of the respiratory epithelium to the exclusion of microbes and particles, but also to the control of the inflammatory and immune responses in the airways and in the alveoli. Epithelial cells also mediate the active transport of polymeric immunoglobulin-A from the lamina propria to the airway lumen through the polymeric immunoglobulin receptor. The role of IgA in the defence of mucosal surfaces has now expanded from a limited role of scavenger of exogenous material to a broader protective function with potential applications in immunotherapy. In addition, the recent identification of receptors for IgA on the surface of blood leukocytes and alveolar macrophages provides an additional mechanism of interaction between the cellular and humoral immune systems at the level of the respiratory tract.
Magnetic resonance imaging of the pharynx in OSA patients and healthy subjects
Authors: Ciscar M.A. , Juan G. , Martínez V. , Ramón M. , Lloret T. , Mínguez J. , Armengot M. , Marín J. , Basterra J.
Published: July 2002

Obstructive sleep apnoea (OSA) occurs because of recurrent narrowing and occlusion of the velopharynx (VP) during sleep. The specific cause of OSA is unknown. Cephalometric radiography, fibreoptic nasopharyngoscopy, acoustic reflection techniques, and computerized tomography have limitations (dynamic and tridimensional evaluation) in the mechanism of occlusion investigation. Static and dynamic examination of the soft tissue structures surrounding the upper airway during the respiratory cycle in wakefulness and sleep, can lead to a better understanding of the process.

Ultrafast magnetic resonance imaging (one image per 0.8 s) was used to study the upper airway and surrounding soft tissue in 17 patients with OSA during wakefulness and sleep, and in eight healthy subjects whilst awake.

The major findings of this investigation in the 25 subjects were as follows: 1) the VP was smaller in apnoeic patients, only during part of the respiratory cycle; 2) the variation in VP area during the respiratory cycle was greater in apnoeic patients than in controls, particularly during sleep, suggesting an increased compliance of the VP in these patients; 3) VP narrowing was similar in the lateral and anterior-posterior dimensions, both in controls and apnoeic patients while awake; apnoeic patients during sleep have a more circular VP upon reaching the minimum area; 4) there was an inverse relationship between dimensions of the lateral pharyngeal walls and airway area, probably indicating that lateral walls are passively compressed or stretched as a result of changes in the airway calibre; and 5) soft palate and parapharyngeal fatpads were larger in apnoeic patients, although their role in the genesis of OSA is uncertain.

It was concluded that changes in the velopharynx area and diameter during the respiratory cycle are greater in apnoeic patients than in normal subjects, particularly during sleep. This suggests that apnoeic patients have a more collapsible velopharynx, this being the main mechanism of obstruction.
Plethysmography for the assessment of pneumococcal pneumonia and passive immunotherapy in a mouse model
Authors: de Hennezel L. , Debarre S. , Ramisse F. , Delamanche S. , Harf A. , Alonso J‐M. , Calvet J‐H.
Published: July 2002

The increasing prevalence of resistance to antibiotics ofStreptococcus pneumoniae, the main causative agent of community-acquired bacterial pneumonia, necessitates the development of both new therapeutic strategies and noninvasive methods in order to evaluate their efficacy.

The efficacy of passive immunotherapy with human intravenous immunoglobulin (IVIG) or solvent alone, administered intranasally or intravenously, was evaluated in a mouse model of acute pneumonia. Lung bacterial load was also evaluated, using a classical but invasive method, as was respiratory function (minute ventilation, respiratory frequency and tidal volume) using plethysmography, a simple noninvasive method commonly used in inhalation toxicology, but not previously used to assess respiratory infection.

Forty-eight hours after infectious challenge, the lung bacterial load was significantly lower in IVIG-treated mice than in untreated mice. At the same time, minute ventilation was significantly lower than reference values for untreated mice (36±3versus57±8 mL·min−1, p<0.01, and 31±2versus50±5 mL·min−1, p<0.01 for intranasal and intravenous administration of solvent, respectively) but not in mice treated with IVIG by either route of administration.

Plethysmography therefore appears to be a simple and reliable test for the follow-up of acute respiratory infection.
Dynamic respiratory system mechanics in infants during pressure and volume controlled ventilation
Authors: Kessler V. , Guttmann J. , Newth C.J.L.
Published: July 2002

Dynamic respiratory system mechanics can be determined using multiple linear regression (MLR) analysis. There is no need for a particular ventilator setting or for a special ventilatory manoeuvre. The purpose of this study was to investigate whether or not different ventilator modes and the flow-dependent resistance of the endotracheal tube (ETT) influence the determination of resistance and compliance by MLR.

Ten paediatric patients who were on controlled mechanical ventilation for various disorders were investigated. The ventilator modes were changed between pressure control (PC) and volume control (VC). Flow and airway pressure were measured and tracheal pressure was continuously calculated. Each mode was applied for 3 min, and 10 consecutive breaths at the end of each period were analysed. Respiratory mechanics were determined by MLR based on either airway pressure, thus including the resistance of the ETT, or tracheal pressure.

Resistance was found to be slightly higher in PC than in VC. There was no effect on determination of compliance between the different modes. Elimination of the flow-dependent resistance of the ETT preserved the differences between the modes.

The authors conclude that using multiple linear regression compliance is not affected by the actual ventilator mode, whereas resistance is.
Fungal infections in transplant recipients
Authors: Nicod L.P. , Pache J‐C. , Howarth N.
Published: July 2002

Fungi are ubiquitous and the respiratory tract is exposed to aerosolized spores of both fungi that are “pathogenic” even in the normal host, such asCryptococus neoformans, and those that are “opportunistic”, such asCandidaandAspergillusspecies, among others. Although these latter species may occasionally form fungal balls or induce allergic phenomena in the normal host, they produce more invasive diseases in immunosuppressed patients. Among these diseases, pseudomembranous aspergillosis has recently been described.

The diagnostic approach to these entities, and, in particular, the thin dividing line between colonization and infection are addressed, along with the diagnostic value of the various procedures.

New prophylactic regimens are reviewed such as the possibility of using amphotericin aerosols in combination with systemic azole administration.

The authors would emphasize the importance of restoring lung defences by not only decreasing immunosuppressive regimens but also considering the use of newly available recombinant cytokines such as growth factors, to reduce neutropenia, for instance, in addition to antifungal drugs when infection is diagnosed. However, immunomodulation procedures are far from being well established.
High short-term mortality following lung biopsy for usual interstitial pneumonia
Authors: Utz J.P. , Ryu J.H. , Douglas W.W. , Hartman T.E. , Tazelaar H.D. , Myers J.L. , Allen M.S. , Schroeder D.R.
Published: July 2002

Usual interstitial pneumonia (UIP) is a specific histological pattern of interstitial pneumonia most often associated with the clinical syndrome of idiopathic pulmonary fibrosis (IPF). There is controversy regarding the use of surgical lung biopsy in the diagnosis of UIP, and the risk of lung biopsy in these patients is largely unknown. This study investigated the 30 day surgical mortality rate in patients undergoing surgical lung biopsy for UIP.

Patients undergoing surgical lung biopsy over a 10-yr period from 1986–1995 with the ultimate diagnosis of UIP (with or without underlying connective tissue disease) were identified. Pathology, computed tomography, medical records, and survival were assessed.

Ten of sixty patients with usual interstitial pneumonia were found to be dead within 30 days of surgical biopsy. All of these were patients with idiopathic UIP, unassociated with connective tissue disease (clinical condition of IPF).

In conclusion, patients with usual interstitial pneumonia of the idiopathic type, who present with atypical features, may be at higher risk for death following surgical biopsy than patients presenting with more typical features or patients with other interstitial illnesses.
Dose dependent increased mortality risk in COPD patients treated with oral glucocorticoids
Authors: Schols A.M.W.J. , Wesseling G. , Kester A.D.M. , de Vries G. , Mostert R. , Slangen J. , Wouters E.F.M.
Published: July 2002

Systemic corticosteroids are often administered in COPD patients. The relationship between systemic glucocorticoids and mortality in patients with moderate to severe chronic obstructive pulmonary disease (COPD) was retrospectively analysed. Baseline characteristics of the patients, in stable clinical condition, were collected on admission to a pulmonary rehabilitation centre. Overall mortality was asessed at the end of follow-up. The Cox proportional hazards model was used to quantify the relationship between glucocorticoid use, distinguishing administration route (oral/inhalation) and oral dose, and overall mortality, adjusted for the influence of age, sex, smoking, lung function, resting arterial blood gases and body mass index.

On multivariate analysis, oral glucocorticoid use at a (prednisone equivalent) dose of 10 mg·day−1without inhaled glucocorticoids, was associated with an increased risk (RR=2.34, 95% confidence interval (CI) 1.24–4.44) while 15 mg·day−1carried a relative risk of 4.03, CI=1.99–8.15). A significant interaction was observed between inhaled and oral glucocorticoid use. Combined with inhaled glucocorticoids, the relative risk of oral glucocorticoid use appeared to be significantly smaller.

It is concluded that in severe chronic obstructive pulmonary disease, maintenance treatment with oral glucocorticoids is associated with increased mortality in a dose-dependent manner. Since the present study design cannot exclude the possibility of bias by indication, further prospective studies are indicated using a broader patient characterization.
Utility of echocardiography in assessment of pulmonary hypertension secondary to COPD
Authors: Higham M.A. , Dawson D. , Joshi J. , Nihoyannopoulos P. , Morrell N.W.
Published: July 2002

Studies have confirmed the close correlation of echocardiographically estimated pulmonary arterial pressure with invasive measurements in patients with chronic obstructive pulmonary disease (COPD), but there are few data on utility of echocardiographic measurement in assessing pulmonary arterial hypertension (PH) in COPD and correlation with pulmonary function tests.

Presence or absence of tricuspid regurgitation (TR) was determined by Doppler echocardiography in 73 consecutive COPD patients attending a hospital outpatient clinic. Transtricuspid pressure gradient (TTPG) was calculated. PH was defined as TTPG ≥30 mmHg. Patients also underwent spirometry, forced expiratory volume in one second (FEV1), single breath gas transfer (carbon monoxide transfer coefficient; (KCO) and carbon monoxide diffusing capacity of the lung;DL,CO) and arterial blood gas measurement.

Measurable TR was observed in 56/73 patients (77%). There were no differences between the group in which TR was observed compared to that in which it was absent, with regard to age, smoking history nor pulmonary function variables. PH was seen in 31/56 cases (55%), with good reproducibility. There were statistically significant correlations of TTPG with FEV1(r=−0.26, p=0.05),KCO(r=−0.31, p=0.04) andDL,CO(r=−0.42, p=0.006) expressed as % pred. Stepwise regression analysis showed that age andKCOcombined provide a multivariate model for prediction of TTPG.

It is concluded the presence and degree of pulmonary arterial hypertension is readily and reliably determined by echocardiography in the majority of chronic obstructive pulmonary disease patients. Pulmonary arterial hypertension is common in severe chronic obstructive pulmonary disease and transtricuspid pressure gradient correlates with spirometry and indices of gas transfer, similar to previous invasive studies. In view of the adverse effects of pulmonary arterial hypertension on morbidity and mortality routine echocardiography in patients with severe chronic obstructive pulmonary disease may be warranted.
Benefit from the inclusion of self-treatment guidelines to a self-management programme for adults with asthma
Authors: Klein J.J. , van der Palen J. , Uil S.M. , Zielhuis G.A. , Seydel E.R. , van Herwaarden C.L.A.
Published: July 2002

This study assessed the long-term efficacy of adding self-treatment guidelines to a self-management programme for adults with asthma.

In this prospective randomized controlled trial, 245 patients with stable, moderate to severe asthma were included. They were randomized into a self-treatment group (group S) and a control group (group C). Both groups received self-management education. Additionally, group S received self-treatment guidelines based on peak expiratory flow (PEF) and symptoms. Outcome parameters included: asthma symptoms, quality of life, pulmonary function, and exacerbation rate. The 2‐yr study was completed by 174 patients.

Both groups showed an improvement in the quality of life of 7%. PEF variability decreased by 32% and 29%, and the number of outpatient visits by 25% and 18% in groups S and C, respectively. No significant differences in these parameters were found between the two groups. After 1 yr, patients in both groups perceived better control of asthma and had more self-confidence regarding their asthma. The latter improvements were significantly greater in group S as compared to group C. There were no other differences in outcome parameters between the groups.

Individual self-treatment guidelines for exacerbations on top of a general self-management programme does not seem to be of additional benefit in terms of improvements in the clinical outcome of asthma. However, patients in the self-treatment group had better scores in subjective outcome measures such as perceived control of asthma and self-confidence than patients in the control group.
IL‐4 fails to regulatein vitroberyllium-induced cytokines in berylliosis
Authors: Maier L.A. , Sawyer R.T. , Tinkle S.S. , Kittle L.A. , Barker E.A. , Balkissoon R. , Rose C. , Newman L.S.
Published: July 2002

Bronchoalveolar lavage (BAL) cells from patients with chronic beryllium disease (CBD) have been used to evaluate the beryllium-specific immune response and potential immunotherapeutics. Beryllium induces interferon‐γ (IFN‐γ), interleukin‐2 (IL‐2), tumour necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6) and interleukin‐10 (IL‐10) from BAL cells. An antibody to IL‐2 and recombinant human (rHu) IL‐10 is able to partially suppress the beryllium-stimulated immune response. To obtain BAL cells, bronchoscopy is required, providing risk to the patient and a limited number of cells to study the immune response. As a result, the objectives of the study were to determine 1) whether CBD peripheral blood mononuclear cells (PBMNs) stimulated with beryllium would produce a similar cytokine pattern as BAL cells, and 2) whether this response could be modulated by interleukin‐4 (IL‐4), an immunomodulatory cytokine.

CBD and normal individuals' PBMN and BAL cells were stimulated with and without beryllium sulfate. To modulate this antigen-stimulated response, we added rHu IL‐4 to the unstimulated and beryllium-stimulated cells. IFN‐γ, IL‐2, TNF‐α, IL‐6 and IL‐10 cytokine concentrations were determined from cell supernatants by enzyme-linked immunosorbent assays (ELISA), while IL‐4 messenger ribonucleic acid (mRNA) was assessed using polymerase chain reaction (PCR).

Beryllium did not stimulate any of these cytokines from normal PBMNs. Increasing levels of IL‐6 and TNF‐α were produced constituitively by CBD PBMNs over time. Compared to the unstimulated CBD PBMNs, beryllium stimulated significant IFN‐γ, TNF‐α, IL‐2, IL‐6 and IL‐10 production. This response was similar to that stimulated from CBD BAL cells, although of a much lower magnitude. Low levels of IL‐4 mRNA were found in CBD and control PBMNs, which were not increased with beryllium stimulation. The beryllium-stimulated cytokine levels were not decreased by the addition of IL‐4. IL‐4 was unable to downregulate any of these beryllium-stimulated cytokines from CBD BAL cells or increase IL‐4 mRNA from either CBD PBMN or BAL cells, and thus is an unlikely immunomodulatory agent in CBD.

From the data, it was concluded that chronic beryllium disease peripheral blood mononuclear cells provide a model to study the beryllium-stimulated immune response. Interleukin‐4's inability to downregulate any of the beryllium-stimulated cytokines makes it an unlikely therapeutic candidate in chronic beryllium disease.
Higher occurrence of asthma-related symptoms in an urban than a suburban area in adults, but not in children
Authors: Wieringa M.H. , Vermeire P.A. , Van Bever H.P. , Nelen V.J. , Weyler J.J.
Published: July 2002

In young adults, a higher occurrence of asthma-related symptoms was found in an urban than an adjacent suburban area in a survey performed in 1991. The authors now wondered whether such differences could be established in other age groups.

The present study (in 1996) included 14,299 subjects, aged 5–75 yrs, of a random sample of the general population in the same two adjacent areas: the centre of Antwerp (Belgium) and its south suburban border. The standardized European Community Respiratory Health Survey (ECRHS) and International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires were used to assess the occurrence of asthma-related symptoms.

Higher rates were confirmed in urban compared to suburban Antwerp in adults (20–75 yrs), but no such area differences were found in children (5–8 and 12–15 yrs). Adjustment for a number of recorded risk factors did not seem to affect the area differences in asthma-related symptoms. Comparing the survey results of 1991 and 1996 in 20–44 yr old adults, the findings suggest a slight increase in reported respiratory symptoms in both areas.

A higher occurrence of asthma symptoms was observed in the urban than suburban area in adults, but not in children. This might be explained by a progressive effect of long-term exposure to the “urban environment”. However, longitudinal studies are necessary to further clarify the factors accounting for these age-related area differences.
Ultrafine particles in urban air and respiratory health among adult asthmatics
Authors: Penttinen P. , Timonen K.L. , Tiittanen P. , Mirme A. , Ruuskanen J. , Pekkanen J.
Published: July 2002

Airborne particles are associated with adverse health effects and contribute to excess mortality in epidemiological studies. A recent hypothesis proposes that the high numbers of ultrafine (<0.1 μm diameter) particles in ambient air might provoke alveolar inflammation and subsequently cause exacerbations in pre-existing cardiopulmonary diseases.

To test the hypothesis adult asthmatics were followed with daily peak expiratory flow (PEF) measurements and symptom and medication diaries for six months, while simultaneously monitoring particulate pollution in ambient air. The associations between daily health endpoints of 57 asthmatics and indicators of air pollution were examined by multivariate regression models.

Daily mean number concentration of particles, but not particle mass (PM10(particle mass <10 μm), PM2.5–10, PM2.5, PM1), was negatively associated with daily PEF deviations. The strongest effects were seen for particles in the ultrafine range. However, the effect of ultrafine particles could not definitely be separated from other traffic generated pollutants, namely nitric oxide, nitrogen dioxide and carbon monoxide. No associations were observed with respiratory symptoms or medication use.

Particle mass measurements can be strongly influenced by mechanically produced, soil-derived particles, which may not be associated with adverse health effects. Therefore, air quality monitoring should include particle number concentrations, which mainly reflect ultrafine particles.
Elevated nitrite in breath condensates of children with respiratory disease
Authors: Formanek W. , Inci D. , Lauener R.P. , Wildhaber J.H. , Frey U. , Hall G.L.
Published: July 2002

The aim of the study was to determine the differences in nitrite, in the exhaled breath condensates of healthy children and those children with asthma, cystic fibrosis (CF) and nonasthmatic, episodic cough.

Breath condensates were obtained from 66 children (43 males:23 females, 3.1–16 yrs) and included 29 asthmatics, 12 clinically stable CF patients, 12 children with cough but not asthma and 13 healthy volunteers. The collected condensate was assayed colourimetrically using the Griess reaction to determine nitrite concentrations.

Patients with CF (median: 5–95% percentiles; 2.02: 0.43–6.37 µM) or asthma (2.10: 0.63–5.45 µM) had significantly higher levels of nitrite compared to healthy subjects (0.41: 0.13–1.83 µM; p<0.05) or subjects with cough (0.75: 0.03–1.75 µM; p<0.05).

Airway inflammation, as assessed by the nitrite in breath condensates, is present in children with asthma and cystic fibrosis, but not those children with nonasthmatic, episodic cough. Nitrite can be conveniently, cheaply and rapidly measured in breath condensates of children as young as 3 yrs of age, and may prove useful for the assessment of airway inflammation in children with respiratory disease.
Effect of inhaled heparin on lung function and coagulation in healthy volunteers
Authors: Bendstrup K.E. , Gram J. , Jensen J.I.
Published: July 2002

The aim of the present study was to investigate the safety of increasing doses of a well-defined lower respiratory tract (LRT) dose of inhaled heparin with regard to pulmonary function and coagulation.

Ten volunteers inhaled heparin from Sidestream jet nebulizers loaded with 100,000, 200,000, 300,000 or 400,000 International Units (IU) of heparin. Lung function, antifactor (anti)-Xa, activated partial thromboplastin time (APTT), tissue factor pathway inhibitor (TFPI), whole blood clotting time, platelets, von Willebrand factor, and C‐reactive protein were determined before and 1, 3, 6, and 24 h after inhalation.

The highest LRT dose was 32,000 IU heparin. Inhaled heparin did not affect pulmonary function. The area under the curve of the anti-Xa activity increased with increasing doses of heparin (p=0.005), but remained unchanged for all other variables. Peak anti-Xa activity was 0.113 IU·mL−16 h after inhalation of 400,000 IU heparin. When compared to baseline values: anti-Xa increased after 200,000 (p=0.03), 300,000 (p=0.004), and 400,000 IU (p=0.002) heparin; APTT increased to a maximum of 1.03 6 h after inhalation of 400,000 IU heparin (p=0.05); TFPI increased after 100,000 (p=0.01), 200,000 (p=0.01), 300,000 (p=0.006) and 400,000 IU (p<0.001).

Inhaled heparin delivery of 32,000 International Units to the lower respiratory tract can safely be inhaled for clinical or research purposes.
Noninvasive ventilation in cystic fibrosis patients with acute or chronic respiratory failure
Authors: Madden B.P. , Kariyawasam H. , Siddiqi A.J. , Machin A. , Pryor J.A. , Hodson M.E.
Published: July 2002

The experience of using noninvasive ventilation (NIV) in 113 adult cystic fibrosis (CF) patients with chronic respiratory failure, during episodes of acute deterioration in respiratory function is reported.

The patients aged 15–44 yrs were divided into three groups. Group A consisted of 65 patients (median forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) 0.7/1.4 L) who were on a lung transplant waiting list. Group B consisted of 25 patients (median FEV1/FVC 0.7/1.4 L) who were being evaluated for lung transplantation. Group C consisted of 23 patients (median FEV1/FVC 0.6/1.2 L) who were not being considered for lung transplantation.

The mean duration of NIV support for groups A, B and C was 61 (range: 1–600) days, 53 (1–279) days and 45 (0.5–379) days respectively. Twenty-three patients in group A subsequently received lung transplantation and 12 of these patients had a median survival of 39 months postsurgery. Thirty-nine patients died and three awaited transplantation. Five patients in group B received a transplant four of whom survived; thirteen patients died and seven awaited transplantation. Twenty patients in group C died.

Noninvasive ventilation improved hypoxia but failed to correct hypercapnia in these cystic fibrosis patients. Noninvasive ventilation is useful in the treatment of acute episodes of respiratory failure in cystic fibrosis patients with end-stage lung disease who have been accepted, or are being evaluated, for lung transplantation. For these patients, there is a possibility of prolonging life if they are successfully treated for their acute episode of respiratory failure until transplantation. In this group, treatment is not merely prolonging the process of dying.
Incidence of asthma and respiratory symptoms by sex, age and smoking in a community study
Authors: Eagan T.M.L. , Bakke P.S. , Eide G.E. , Gulsvik A.
Published: July 2002

The purpose of this study was to establish incidence rates for a wide range of respiratory symptoms and asthma, and relate them to sex, age, and smoking habits.

A cohort established in 1985 as a random sample from the population of Western Norway, aged 15–70 yrs, was followed-up in 1996–1997. Of the initial cohort of 3,786 subjects, a total of 2,819 replied to mailed questionnaires at both baseline and follow-up.

The 11‐yrs cumulative incidence of asthma was 4.0% in males and 3.5% in females. For respiratory symptoms, the cumulative incidences for both sexes varied between 2.0% (dyspnoea grade 4) and 25.8% (wheezing), being higher in females than males for most symptoms. For calculation of odds ratios (ORs) multivariate logistic regression analyses were used. The sex and smoking-adjusted incidences increased by age for all symptoms except wheezing and attacks of dyspnoea. Those starting to smoke within the follow-up had ORs of 1.9–2.2 for the cough symotoms compared to never-smokers, after adjusting for sex, age, and pack-yrs.

To conclude, the 11‐yrs incidence of dyspnoea increased with increasing pack-yrs, after adjusting for sex, age, and changes in smoking habits. This indicated that when analysing other risk factors, adjustment has to be made for the risks posed by smoking, sex and age.
Diagnosis and treatment of invasive pulmonary aspergillosis in neutropenic patients
Authors: Reichenberger F. , Habicht J.M. , Gratwohl A. , Tamm M.
Published: July 2002

Invasive pulmonary aspergillosis is a major cause of morbidity and mortality in neutropenic patients.

Microbiological and serological tests are of limited value. The diagnosis should be considered in neutropenic patients with fever not responding to antibiotics, and typical findings on thoracic computed tomography scan. Whenever possible, diagnosis should be confirmed by tissue examination. Newer techniques, such as polymerase chain reaction may change the current diagnostic approach.

Therapeutic strategies consist of prophylaxis in risk groups and the early application of antifungal agents in suspected or probable disease. Amphotericin B as desoxycholate or lipid formulation is the current standard medication in invasive infection, although it has major side effects. Its role is challenged by the new azole derivates, such as itraconazole and voriconazole, and the new echinocandins. Additional therapies with cytokines, such as granulocyte macrophage colony stimulating factor and interferon‐γ, and with granulocyte transfusions are under evaluation. In selected cases lung resection is of proven diagnostic and therapeutic value.

This paper analyses the current understanding of the pathogenesis and epidemiology of invasive aspergillosis and reviews the actual diagnostic and therapeutic strategies for invasive pulmonary aspergillosis in neutropenic patients.
Statin-induced fibrotic nonspecific interstitial pneumonia
Authors: Lantuejoul S. , Brambilla E. , Brambilla C. , Devouassoux G.
Published: July 2002

Statins inhibit the 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase, reduce the serum level of low-density lipoprotein cholesterol, and are extensively prescribed to prevent cardiovascular mortality and morbidity. Few systemic adverse effects, such as pseudopolymyositis, lupus-like syndromes, and anecdotal hypersensitivity pneumonitis, have been reported.

A simvastatin-induced diffuse interstitial pneumonia associated with a nonspecific interstitial pneumonia pattern at histological analysis is repoted here. Ultrastructural analysis showed a diffuse cytoplasmic accumulation of intralysosomial lamellar inclusions in type II pneumonocytes, histiocytes and endothelial cells, suggesting a shared pathogenesis with amphiphilic drug-induced toxic lung injury. Because statins are increasingly prescribed, statin-induced interstitial lung disorders may be more frequently observed and early recognition will be required.
European framework for tuberculosis control and elimination in countries with a low incidence
Authors: Broekmans J.F. , Migliori G.B. , Rieder H.L. , Lees J. , Ruutu P. , Loddenkemper R. , Raviglione M.C.
Published: July 2002

As countries approach the elimination phase of tuberculosis, specific problems and challenges emerge, due to the steadily declining incidence in the native population, the gradually increasing importance of the importation of latent tuberculosis infection and tuberculosis from other countries and the emergence of groups at particularly high risk of tuberculosis.

Therefore, a Working Group of the World Health Organization (WHO), the International Union Against Tuberculosis and Lung Disease (IUATLD) and the Royal Netherlands Tuberculosis Association (KNCV) have developed a new framework for low incidence countries based on concepts and definitions consistent with those of previous recommendations from WHO/IUATLD Working Groups.

In low-incidence countries, a broader spectrum of interventions is available and feasible, including: 1) a general approach to tuberculosis which ensures rapid detection and treatment of all the cases and prevention of unnecessary deaths; 2) an overall control strategy aimed at reducing the incidence of tuberculosis infection (risk-group management and prevention of transmission of infection in institutional settings) and 3) a tuberculosis elimination strategy aimed at reducing the prevalence of tuberculosis infection (outbreak management and provision of preventive therapy for specified groups and individuals).

Government and private sector commitment towards elimination, effective case detection among symptomatic individuals together with active case finding in special groups, standard treatment of disease and infection, access to tuberculosis diagnostic and treatment services, prevention (e.g.through screening and bacille Calmette-Guéria immunization in specified groups), surveillance and treatment outcome monitoring are prerequisites to implementing the policy package recommended in this new framework document.
Bronchodilator responsiveness and serum total IgE levels in families of probands with severe early-onset COPD
Authors: Celedon JC , Speizer FE , Drazen JM , Weiss ST , Campbell EJ , Carey VJ , Reilly JJ , Ginns L , Silverman EK
Published: July 2002

Bronchodilator responsiveness has been associated with a subsequent accelerated decline in forced expiratory volume in one second (FEV1). Therefore, bronchodilator responsiveness and total serum immunoglobulin E(IgE) levels were assessed in 184 adult first-degree relatives of probands with severe early-onset chronic obstructive pulmonary disease (COPD) and a control group. Greater bronchodilator responsiveness was found among current smokers or exsmokers who were first-degree relatives of early-onset COPD probands than in currently or exsmoking controls, expressed as increase in FEV1 as a percentage of baseline (5.8+/-8.1 versus 2.9+/-5.1%, p<0.01), absolute increase in FEV1 from baseline (120+/-130 versus 60+/-110 mL, p<0.05), and increase in FEV1 as a percentage of the predicted value (3.6:4.1 versus 2.2+/-3.9%, p<0.05). However, elevated total serum IgE levels were not found in first-degree relatives of early-onset COPD probands compared with control subjects. The increased bronchodilator responsiveness among currently smoking/exsmoking first-degree relatives of early-onset COPD probands suggests that these individuals may have enhanced susceptibility to the detrimental effects of cigarette smoking.