bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential activity of nitric oxide synthase in human nasal mucosa and polyps
Authors: Ramis I , Lorente J , Rosello-Catafau J , Quesada P , Gelpi E , Bulbena O
Published: July 2003

Nitric oxide (NO) plays an important regulatory role in airway function and seems to be implicated in the pathophysiology of several airway diseases. To better understand the involvement of NO in the upper airways, we examined the presence of nitric oxide synthase (NOS) activity in human nasal mucosa and nasal polyp tissues. Nasal mucosa was obtained from seven patients undergoing septoplasty, and nasal polyps came from nine patients following polypectomy. NOS activity was quantified in tissue homogenates using the citrulline release assay and localized in tissue sections using reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry. The results showed that nasal polyps (n = 9) contained higher levels of total NOS activity (mean +/- SD 5.94 +/- 5.71, range 1.29-18.0 pmol.min-1.mg protein) than nasal mucosa tissues (n = 7) (0.28 +/- 0.22, range 0.01-0.57 pmol.min-1.mg protein). In addition, nasal polyps mainly contained inducible NOS activity (4.67 +/- 4.57, range 1.23-15.5 pmol.min-1.mg protein) whereas in nasal mucosa all NOS activity detected was in constitutive form. In both cases, NOS activity was localized in the epithelial cells. Since NO synthase is induced in inflamed upper airways, we conclude that NO may be an important inflammatory mediator in the respiratory system and that the epithelium may be a source of NO production in the human upper airways.
Association between toluene diisocyanate-induced asthma and DQB1 markers: a possible role for aspartic acid at position 57
Authors: Balboni A , Baricordi OR , Fabbri LM , Gandini E , Ciaccia A , Mapp CE
Published: July 2003

Toluene diisocyanate (TDI) is the most common cause of occupational asthma in western countries. The aim of this study was to investigate whether genetic factors are involved in toluene diisocyanate-induced asthma. We studied the frequency of human leucocyte antigen (HLA) class II genetic markers in three groups of subjects: 1) subjects with TDI-induced asthma (n = 30); 2) exposed subjects with no history of TDI-induced asthma (n = 12); and 3) normal subjects not exposed to TDI (n = 126). Venous blood samples were collected from the three groups and the polymorphic second exon of DQA and DQB genes was amplified by the polymerase chain reaction (PCR) method. Evaluation of HLA class II gene products in TDI-induced asthma cases showed a positive association with HLA-DQB1 * 0503 and a negative association with HLA-DQB1 * 0501 alleles, which differed at residue 57 for a single amino acid, i.e. aspartic acid in DQB1 * 0503 and valine in DQB1 * 0501. No significant difference was found in the distribution of DQA1 alleles between asthmatics and controls. Our results confirm the hypothesis that HLA-DQB1 * 0503 has a role in conferring susceptibility to TDI-induced asthma and that residue 57 of HLA-DQB1 is a potentially critical location.
Absence of relationship between degree of nonspecific and specific bronchial responsiveness in occupational asthma due to platinum salts
Authors: Merget R , Dierkes A , Rueckmann A , Bergmann EM , Schultze-Werninghaus G
Published: July 2003

There is evidence that bronchial responsiveness to allergen is quantitatively correlated with bronchial responsiveness to nonspecific stimuli in subjects with allergic asthma. This association has been questioned in occupational asthma due to low molecular weight substances. It was the aim of this study to assess the quantitative association of bronchial responsiveness to methacholine (MCh) and platinum salts (Pt), in the form of hexachloroplatinic acid, in workers with occupational asthma due to platinum salts. Fifty seven subjects with exposure to Pt, work-related asthma, and a positive bronchial challenge with Pt, underwent skin prick tests with Pt and bronchial challenge with MCh. Using the provocation concentration causing a > or = 50% fall in specific airway conductance (PC50sGaw(Pt)) as dependent variable, anamnestic data (period from first symptoms to removal, period between removal from exposure and diagnosis, and smoking), season of the investigation, skin prick tests with environmental allergens, total immunoglobulin E (IgE), skin reactivity to Pt (Pt concentration causing a 2 mm wheal), and PC50sGaw(MCh) were included as independent variables for regression analysis. Fifty two subjects (91%) showed a PC50sGaw(MCh) < 8 mg.mL-1 (geometric mean for all subjects 1.6 mg.mL-1). Responsiveness to Pt varied widely between subjects (geometric mean of PC50sGaw 9 x 10-5 mol.L-1, range 2 x 10-7 to 10-2 mol.L-1). There was no univariate correlation between bronchial responsiveness to MCh and Pt, but there was a correlation between skin reactivity to Pt and PC50sGaw(Pt) (r = 0.6). This association could not be improved by considering PC50sGaw(MCh), the period from first symptoms to removal, or the period between removal from exposure and diagnosis. The parameters that showed the highest (negative) associations with PC50sGaw(Pt) were skin reactivity to Pt and the period between removal from exposure and diagnosis (r = 0.65). We conclude that there is a moderate association between bronchial responsiveness to platinum salts and skin reactivity to platinum salts. However, there is no association between methacholine responsiveness and bronchial responsiveness to allergen in occupational asthma due to platinum salts.
The effect of inhaled heparin on bronchial reactivity to sodium metabisulphite and methacholine in patients with asthma
Authors: Pavord I , Mudassar T , Bennett J , Wilding P , Knox A
Published: July 2003

Inhaled heparin inhibits the early response to allergen and exercise-induced asthma, probably by inhibiting mast cell mediator release. Recent animal studies suggest that heparin might also inhibit cholinergic neurotransmission in asthma by restoring inhibitory M2 receptor function. We have tested the hypothesis that heparin inhibits neurally-mediated bronchoconstriction in asthma by examining the effect of inhaled heparin on bronchial reactivity to sodium metabisulphite. We also examined the effect of inhaled heparin on methacholine-induced bronchoconstriction to exclude a direct effect on airway smooth muscle. Eleven patients with mild asthma inhaled nebulized heparin (1,000 U.kg-1) or placebo (normal saline) in a randomized, double-blind fashion, 10 min before a challenge with sodium metabisulphite. Nine patients were also challenged with methacholine after the same dose of heparin or placebo. Inhaled heparin did not significantly change forced expiratory volume in one second (FEV1), nor did it alter the provocative dose of sodium metabisulphite or methacholine required to cause a 20% fall in FEV1 (PD20). Geometric mean sodium metabisulphite PD20 was 2.54 and 2.15 mumol after placebo and heparin, respectively (mean difference -0.24 doubling doses; 95% confidence interval (95% CI) -0.64-0.17). Geometric mean methacholine PD20 was 1.00 and 1.51 mumol after placebo and heparin, respectively (mean difference 0.6 doubling doses; 95% CI -0.25-1.5). Thus, heparin inhaled at doses sufficient to inhibit allergen and exercise-induced bronchoconstriction has no effect on the response to sodium metabisulphite and methacholine challenge in asthma. This argues against an inhibitory effect on neural pathways or airway smooth muscle.
Role of cyclic AMP in the modulation of IgE production by the beta 2-adrenoceptor agonist, fenoterol
Authors: Coqueret O , Demarquay D , Lagente V
Published: July 2003

We have previously demonstrated that the beta 2-adrenoceptor agonist, salbutamol, potentiates the effect of interleukin-4 (IL-4) on immunoglobulin E (IgE) production by human peripheral blood mononuclear cells (PBMC). This study was undertaken to further define the activities of these drugs and the role of cyclic-adenosine monophosphate (cAMP) in the modulation of IgE production. Our results indicate that fenoterol (1 microM) potentiated IL-4-induced IgE production and IgE messenger ribonucleic acid (mRNA) expression. Moreover, this effect was associated with an increase in intracellular cAMP levels. The activities of this drug on IgE production were mimicked by cell permeable cAMP analogues, such as dibutyryl-cAMP (db-cAMP) (100 microM) or Sp-AMP (10 microM). The potentiating effect of fenoterol on IgE production was markedly inhibited in the presence of protein kinase A (PKA) inhibitors: H8 (10 microM) and Rp-AMP (10 microM), suggesting that its effects are likely to depend on the activation of the cAMP pathway. Additionally, the potentiating effect of fenoterol was also blocked in the presence of indomethacin. Fenoterol potentiated IL-4-induced IgE production from purified B-cells activated through their CD40 antigen. This effect was associated with an increase in cellular viability. Therefore, the activities of this drug on PBMC are likely to be mediated by the activation of another cellular type. Taken together, these results show that fenoterol potentiates the IL-4-induced IgE production via the cAMP pathway, but that this enhancement could not be explained by a direct effect on B-lymphocytes.
Skin bruising in asthmatic subjects treated with high doses of inhaled steroids: frequency and association with adrenal function
Authors: Roy A , Leblanc C , Paquette L , Ghezzo H , Cote J , Cartier A , Malo JL
Published: July 2003

High doses of inhaled corticosteroids (ICS) (budesonide and beclo-methasone > or = 800 micrograms.day-1) are commonly used in the treatment of asthma. Some investigators have presented evidence for cutaneous effects (bruising), which suggests systemic absorption. This study aimed to assess the prevalence of skin bruising, relate the occurrence of skin bruising to adrenocortical function, and determine the risk factors for skin bruising. One hundred adult asthmatic subjects taking high doses (800-2,000 micrograms.day-1) of ICS for 3 months or more were recruited in an asthma clinic, and 100 control subjects paired for sex and age were recruited from an ophthalmology out-patient clinic. A detailed questionnaire on asthma, general habits and cutaneous lesions was administered. A cutaneous examination was performed. Urine cortisol levels were assessed on two consecutive days. Blood cortisol level and the response to Cortrosyn injection (60 min test) were evaluated. One hundred adult asthmatics (66 females and 34 males), 73 on beclomethasone and 27 on budesonide, were included. The prevalence of skin bruising was 71% based on the questionnaire (32% in controls) and 48% (39 out of 81 subjects) based on direct examination of the skin. We found a satisfactory association between the response to questionnaire and examination of the skin. Adrenocortical function testing showed that a minority of subjects (14 with at least one abnormal test) had lower urinary or blood cortisol levels. These low cortisol levels occurred in subjects who reported skin bruising. By multiple logistic regression, being a female (odds ratio (OR) = 20; 95% confidence interval (95% CI) = 13-33) and taking ICS for asthma (OR = 12; 95% CI = 8-18) were significantly (t = 5.4) related to the likelihood of developing skin bruising. In addition, among the asthmatic subjects, being older (OR = 1.6; 95% CI = 1.1-2.4/10 yrs interval) (t = 2.3) and being a female (OR = 22; 95% CI = 7-75) (t = 5.0) influenced the occurrence of skin bruising as documented by questionnaire. In asthmatic subjects, taking high doses of ICS is associated with: 1) increased occurrence of skin bruising by comparison with controls, particularly in older subjects; and 2) a generally normal adrenocortical function, although this function is significantly lower in subjects reporting skin bruising.
Relationship of daytime asthma symptom frequency to morning peak expiratory flow
Authors: Atherton HA , White PT , Hewett G , Howells K
Published: July 2003

Since management plans based on peak flow measurements are increasingly used, the relationship between peak flow rate and ensuing symptom frequency is of particular interest to the treatment of asthma. The objective of this study was to examine to what extent morning peak flow was related to symptom frequency during the day. In 168 out of 307 randomly selected adult asthmatics from a general practice population, adequate recordings of morning peak flow (amPF) and symptom frequency during the day (DSF) were obtained for 28 days. In each individual, the relationship between these two variables was studied and the mean values of these two variables over 28 days were calculated. The relationship between the means of the variables was also examined for the group as a whole. In individuals, the correlation between amPF and DSF varied widely; only 16% of patients had a good relationship (Pearson r = -1 to -0.5). For the whole group, the relationship between mean amPF and mean DSF best fitted a curvilinear model (r = -0.6). This was unaffected by age, sex or the use of inhaled steroids. For the majority of asthmatics, morning peak flow may be an unreliable predictor of expected symptoms during that day. Reliance on peak flow measurement as a tool enabling asthmatics to manage their asthma on a daily basis needs to be reconsidered.
Skeletal muscle magnesium and potassium in asthmatics treated with oral beta 2-agonists
Authors: Gustafson T , Boman K , Rosenhall L , Sandstrom T , Wester PO
Published: July 2003

Dietary magnesium has been shown to be important for lung function and bronchial reactivity. Interest in electrolytes in asthma has so far mainly been focused upon serum potassium, especially linked to beta 2-agonist treatment. It is known that serum levels of magnesium and potassium may not correctly reflect the intracellular status. We therefore investigated whether asthmatics treated with oral beta 2-agonists had low magnesium or potassium in skeletal muscle and serum, and whether withdrawal of the oral beta 2-agonists would improve the electrolyte levels. Magnesium and potassium levels in skeletal muscle biopsies, serum and urine were analysed in 20 asthmatics before and 2 months after withdrawal of long-term oral beta 2-agonists, and for comparison in 10 healthy subjects. Skeletal muscle magnesium in the asthmatics was lower both before (3.62 +/- 0.69 mmol.100 g-1 (mean +/- SD)) and after (3.43 +/- 0.60 mmol.100 g-1) withdrawal of oral beta 2-agonists compared with the controls (4.43 +/- 0.74 mmol.100 g-1). Skeletal muscle potassium and serum magnesium did not differ between the groups. Serum potassium was significantly lower both before (4.0 +/- 0.2 mmol.L-1) and after (3.9 +/- 0.2 mmol.L-1) the withdrawal of oral beta 2-agonists compared with the control group (4.2 +/- 0.2 mmol.L-1). The asthmatics had lower skeletal muscle magnesium and lower serum potassium than the healthy controls, both with and without oral beta 2-agonists. Whether the findings are related to asthma pathophysiology or treatment is currently being investigated.
Diaphragm fatigue following maximal ventilation in man
Authors: Hamnegard CH , Wragg S , Kyroussis D , Mills GH , Polkey MI , Moran J , Road J , Bake B , Green M , Moxham J
Published: July 2003

When highly motivated normal subjects perform maximal isocapnic ventilation, a substantial fall in ventilation is observed during the first minute associated with slowing of the maximum relaxation rate (MRR) of the inspiratory muscles. This suggests that these muscles are excessively loaded, raising the possibility that overt contractile failure of the diaphragm contributes to the fall in ventilation. We therefore investigated the effect of maximal isocapnic ventilation (MIV) on twitch transdiaphragmatic pressure (Pdi,Tw) elicited by cervical magnetic stimulation. We measured Pdi,Tw before and after 2 min MIV in nine normal subjects. Initial mean (SD) ventilation for the nine subjects was 196 (15) L.min-1 falling by 35% at 1 min. Pdi,Tw fell following MIV, at 10 min was reduced by 24%, and remained substantially reduced 90 min after MIV. No change in Pdi,Tw was observed during control studies in which subjects were studied with the same protocol but omitting MIV. We conclude that diaphragmatic contractility is reduced after 2 min maximal isocapnic ventilation and diaphragmatic fatigue may be a limiting factor in maximal ventilation in man.
Cardiorespiratory adaptation of COPD patients to physical training on land and in water
Authors: Perk J , Perk L , Boden C
Published: July 2003

Physical training in water might be included in a comprehensive pulmonary rehabilitation programme, but data on the feasibility and safety of this technique in chronic obstructive pulmonary disease (COPD) patients are lacking. We studied cardiorespiratory parameters of 20 stable COPD patients (10 with forced expiratory volume in one second (FEV1) < 35% of predicted value, and 10 with FEV1 > or = 35% pred) on land and in a temperate-controlled pool (32 degrees C) both at rest and during a 15 min submaximal upper body muscle training programme. Compared to resting values on land, we found in water a decrease of systolic and diastolic blood pressure (14 and 6 mmHg, respectively), rate-pressure product (7%) and lung function (vital capacity (VC) 12%, FEV1 14%, peak expiratory flow (PEF) 18%). There were no differences in heart rate, breathing frequency or O2 saturation. The most strenuous exercise in water resulted in a slightly lower O2 saturation compared to work on land (95 and 93%, respectively), and an increase of Borg rating for dyspnoea from 4 to 5. In spite of the restriction of lung function in water, all patients (even those with FEV1 < 35% pred) performed the training in the pool well, without clinically relevant desaturation, arrhythmia or discomfort. No training session was discontinued due to dyspnoea. We conclude that a 15 min session of submaximal physical training in a pool with a water temperature of 32 degrees C is feasible and safe for nonhypoxaemic normotensive COPD patients without cardiac failure.
Separation of airway and tissue properties by transfer respiratory impedance and thoracic gas volume in reversible airway obstruction
Authors: Marchal F , Bouaziz N , Baeyert C , Gallina C , Duvivier C , Peslin R
Published: July 2003

The aim of this study was to establish the ability to estimate separate airway and tissue properties from transfer respiratory impedance (Zrs,tr) data in the presence of airway obstruction. Zrs,tr, thoracic gas volume (TGV) and airway resistance (Raw,pleth) were measured in the presence of obstruction and after use of a bronchodilator (BD) in 13 normal or asymptomatic asthmatic adults and 28 children with symptomatic asthma. An analytical approach was used to solve the equations of a simplified variant of DuBois' model, including airway resistance (Raw*) and inertance (Iaw), tissue compliance (Ct) and resistance (Rt) and pulmonary gas compliance (Cg). The equations of the model could not be reliably solved in four children before BD. Mean Raw,pleth was not different from mean Raw* in adults before (mean +/- SEM) (3.4 +/- 0.5 vs 3.1 +/- 0.3 hPa.s.L-1) or after BD (1.4 +/- 0.2 vs 1.8 +/- 0.2 hPa.s.L-1), or in children after BD (2.9 +/- 0.3 vs 3.2 +/- 0.2 hPa.s.L-1, respectively). In children before BD, Raw* was significantly underestimated compared with Raw,pleth (3.8 +/- 0.4 vs 5.4 +/- 0.6 hPa.s.L-1). Overall, a significant positive correlation was found between the difference [Raw,pleth - Raw*] and Raw,pleth (r = 0.82). In adults, BD induced a decrease in Raw* and Rt, an increase in Ct, and no change in Iaw. In children after BD, there was no significant change in Raw* or Ct, whilst Rt decreased and Iaw increased. Taking Raw,pleth as the gold standard, it is concluded that coherent estimation of parameters of DuBois' model may be obtained from combined Zrs,tr and TGV measurements in normal subjects and moderately obstructed adults, but not in children with significant airway obstruction. This seems to be due to the systematic under-estimation of Raw*.
Respiratory mechanics in patients ventilated for critical lung disease
Authors: Beydon L , Svantesson C , Brauer K , Lemaire F , Jonson B
Published: July 2003

Respiratory mechanics, using flow interruption, was previously studied during the complete breath in healthy ventilated man, numerical techniques relieving constraints regarding flow pattern. The classical linear model of non-Newtonian behaviour was found to be valid. The present study was extended to subjects with critical lung disease. Subjects with acute lung injury (ALI; n = 2), acute respiratory distress syndrome (ARDS; n = 4), and chronic obstructive pulmonary disease (COPD; n = 3) were studied with and without positive end-expiratory pressure (PEEP). Functional residual capacity (FRC) was measured with sulphur hexafluoride (SF6) wash-out. The static pressure-volume (P-V) curve was linear at zero end-expiratory pressure (ZEEP), but nonlinear at PEEP. Its hysteresis was nonsignificant. In ALI/ARDS, PEEP increased lung volume by distension and recruitment, but only by distension in COPD. In ALI/ARDS, resistance was increased, at ZEEP. In COPD, resistance became extremely high during expiration at ZEEP. In ALI/ARDS at ZEEP, non-Newtonian behaviour, representing tissue stress relaxation and pendel-luft, complied with the classical linear model. At PEEP, the non-Newtonian compliance became volume-dependent to an extent correlated to the nonlinearity of the static P-V curve. In COPD, non-Newtonian behaviour was adequately explained only with a model with different inspiratory and expiratory behaviour. The classical model of the respiratory system is valid in ALI/ARDS at ZEEP. More advanced models are needed at PEEP and in COPD.
Risk factors associated with drug-resistant Mycobacterium tuberculosis in Castilla-la-Mancha (Spain)
Authors: Arevalo M , Solera J , Cebrian D , Bartolome J , Robles P
Published: July 2003

The aim of this study was to investigate the incidence of primary and secondary resistance to antituberculosis drugs and the risk factors associated with the resistance in southeast Spain. Our research was based on the clinical histories of 276 patients, diagnosed as having tuberculosis by positive culture, who were tested for drug susceptibility between January 1988 and October 1994. The clinical histories were checked by two independent investigators. Drug-resistant strains were isolated from 24 patients (8.7%). Among the 239 patients without previous tuberculosis therapy, 7 (2.9%) were drug-resistant. Among the 37 patients with previous therapy, 17 (46%) were drug-resistant. Seventeen of the 276 patients (6.2%) had resistance to a single drug. Primary resistance to isoniazid was 1.7%. Previous treatment for tuberculosis (odds ratio (OR) 39.2; 95% confidence interval (95% CI) 10.2-150); hepatic cirrhosis (OR 104; 95% CI 12.8-847); and age 45 yrs and older (OR 4.80; 95% CI 1.15-20.1) were considered risk factors associated with drug-resistant tuberculosis. We conclude that primary and secondary resistance is low in the southeast of Spain and we recommend that susceptibility testing be performed on initial M. tuberculosis isolated from patients with a history of previous tuberculosis therapy, hepatic cirrhosis or more than 44 yrs of age.
Risk factors for tuberculosis among HIV-infected patients in Switzerland. Swiss HIV Cohort Study
Authors: Sudre P , Hirschel B , Toscani L , Ledergerber B , Rieder HL
Published: July 2003

The aim of this study was to determine the risk factors associated with tuberculosis among human immunodeficiency virus (HIV)-infected persons living in Switzerland, a country with low prevalence of tuberculous infection. We performed a nested case-control study and logistic regression. Cases (n = 239) were patients participating in the Swiss-HIV Cohort study (n = 7,103), diagnosed with bacteriologically confirmed tuberculosis. The rest of the cohort population was used as control. Patients from industrialized countries had a risk of tuberculosis similar to those from Switzerland (adjusted odds ratio (OR) 1.1; 95% confidence interval (95% CI) 0.7-1.5); whereas the risk among patients from Eastern Europe (OR 2.8, 95% CI 1.9-3.7), Brazil (OR 10.6; 95% CI 9.6-11.5), and Africa (OR 3.0; 95% CI 2.4-3.6) was markedly higher. Immune suppression, as indicated by low CD4 + cell count, was an independent risk factor for tuberculosis (OR 7.8; 95% CI 7.3-8.3 for patients with CD4 + < 50 cells.mm-3 compared to those with CD4 + > 500 cells.mm-3). Age, sex and HIV-transmission category did not appear to increase the risk of tuberculosis after adjustment for other patient characteristics. In conclusion, in countries of low prevalence of Mycobacterium tuberculosis infection, to originate from a country with high prevalence of tuberculosis infection and to have advanced immunodeficiency are significant risk factors for tuberculosis. They may be used to complement the tuberculin skin test in targeting patients for preventive chemotherapy.
Characteristics of sputum smear-positive tuberculosis patients with and without HIV infection in a hospital in Zimbabwe
Authors: Schoch OD , Rieder HL
Published: July 2003

Human immunodeficiency virus (HIV) infection has a large impact on tuberculosis in Africa. In this study, the prevalence of HIV infection in a population of hospitalized tuberculosis patients in Zimbabwe was determined and demographic characteristics, clinical signs and symptoms, as well as radiographic appearance were compared in tuberculosis patients with and without HIV infection. During a 5 month observation period, information on tuberculosis patients referred to Driefontein Tuberculosis Sanatorium, Mvuma, Zimbabwe was collected, computerized and analysed with commercially available software. Of 467 patients admitted, 255 were sputum smear positive for acid-fast bacilli. Of 196 patients with complete information, 127 (65%) were HIV-seropositive. When compared to the 69 HIV-seronegative patients, HIV-infected patients were not different in age, gender, the period of delay between the onset of symptoms and diagnosis, radiographic appearance, history of previous antituberculosis treatment and symptoms and signs reported, with the exception of herpes zoster and other sexually-transmitted disease. The prevalence of HIV infection in our population of tuberculosis patients was large. However, since demographic and clinical characteristics are remarkably similar in tuberculosis patients with and without HIV infection, case-finding activities need not be altered in the wake of the HIV epidemic.
Evaluation of a western blot serum test for the diagnosis of Mycobacterium tuberculosis infection
Authors: Rovatti E , Corradi MP , Amicosante M , Tartoni PL , Panini W , Ancora A , Cenci AM , Zucchi L , Monno L , Angarano G , Saltini C
Published: July 2003

This study was designed to evaluate the possibility of monitoring Mycobacterium tuberculosis infection using a serological assay. A discriminant score comprising antigen fractions of 38, 28, 24 and 19 kDa, identified in western blots using the Mycobacterium bovis bacille Calmette-Guerin (BCG) A60 antigen complex was established in a sample of 57 purified protein derivative (PPD)-negative and 47 PPD-positive individuals. It was then tested in a group of 140 subjects undergoing BCG vaccination as a model of tuberculosis complex infection and in a group of human immunodeficiency virus (HIV)-infected individuals as a model of cell-mediated immunodeficiency-related risk of tuberculosis. The discriminant score identified 57 out of 57 (100%) PPD-positives and none (0%) of the 47 PPD-negatives. In the BCG vaccinated subjects, 1.4% tested positive before vaccination and 90% after vaccination. In the HIV-positive subjects, 90% of the PPD-positive and 5% of the PPD-negative subjects had a positive score. This study suggests that the western blot discriminant score is an accurate test to survey M. tuberculosis infection in serum samples.
Suppressive effects of Aspergillus fumigatus culture filtrates on human alveolar macrophages and polymorphonuclear leucocytes
Authors: Murayama T , Amitani R , Ikegami Y , Nawada R , Lee WJ , Kuze F
Published: July 2003

Aspergillus spp., especially A. fumigatus (Af) can colonize the airways and the lungs with localized underlying conditions and further invade the surrounding lung tissues, even in subjects without systemic predisposing factors, presumably by escaping the local host defences. To clarify the mechanisms of colonization and invasion of Af, we investigated the in vitro effects of Af culture filtrates (ACFs) on the functions of human alveolar macrophages (AMs), and polymorphonuclear leucocytes (PMNs). ACFs were obtained by culturing clinically isolated Af in Medium-199 at 37 degrees C for 5 days. In the study of phagocytosis of Af conidia by human AMs, 52% of AMs ingested conidia during a 60 min incubation period in Medium-199. However, the percentage decreased to 24% when incubated with a final concentration of 30% ACF in Medium-199. With respect to the antichemotactic activity on human PMNs, 3% ACF was sufficient for significant suppression, and 30% ACF completely inhibited the migration of PMNs. In addition, phorbol myristate acetate (PMA)-induced O2- release from PMNs was significantly suppressed in Medium-199 which included 12.5% ACF or more. The antichemotactic activity of ACF was partially abolished by trypsin or chicken egg ovomacroglobulin. When ACF was separated into two fractions (molecular weight > 10 and < 10 kDa) by dialysis and centrifugation through CL-LGC filters, both fractions retained the antichemotactic activity. We conclude that Af produce several antiphagocytic factors, which can be responsible for the colonization of Af in the bronchopulmonary tissues and allow this species to invade surrounding lung tissues in pulmonary aspergillosis by suppressing local host defences.
Effect of in vitro and in vivo administration of dexamethasone on rat macrophage functions: comparison between alveolar and peritoneal macrophages
Authors: Nakamura Y , Murai T , Ogawa Y
Published: July 2003

Resident alveolar macrophages (AMs) and peritoneal macrophages (PMs), though they originate from common precursor cells, differ morphologically and functionally. The two types of macrophages residing in different tissues may respond differently to glucocorticoids. In the present study, we compared the effects of a synthetic glucocorticoid, dexamethasone (Dex), on rat AMs and PMs with regard to their phagocytic activity and tumour necrosis factor-alpha (TNF-alpha) releasability. In vitro exposure of the macrophages to Dex caused the depression of phagocytic activity of AMs but not of PMs. In contrast, TNF-alpha releasability was depressed in the both types of macrophages, and no difference was found between AMs and PMs in their susceptibility to TNF-alpha regulation by Dex. When Dex was administered subcutaneously into rats, phagocytic activity was severely depressed in AMs but not in PMs. On the other hand, TNF-alpha releasability was depressed both in AMs and PMs by the in vivo Dex administration. The depression in PMs, however, was transitory and less severe than that in AMs. These results suggest that alveolar macrophages and peritoneal macrophages differ intrinsically in responses to glucocorticoid, and that the cell location and the cell's microenvironment can also modulate the effects of glucocorticoid on macrophage functions.
Oxidized BAL fluid proteins in patients with interstitial lung diseases
Authors: Lenz AG , Costabel U , Maier KL
Published: July 2003

Oxygen-derived free radicals, released by phagocytic cells, have been postulated to contribute to lung tissue damage. We therefore investigated oxidative damage to proteins from bronchoalveolar lavage fluid (BALF) as an indicator of oxidative stress and to assess antioxidant defences in the lungs. We examined BAL fluids from patients with interstitial lung diseases, such as idiopathic pulmonary fibrosis (IPF, nonsmokers (NS) and smokers (S)), sarcoidosis (SARC, nonsmokers), and asbestosis (ASB, ex-smokers (EXS)). The oxidation of BALF proteins is accompanied by the introduction of carbonyl groups into their amino acid side-chains and can be quantitated by labeling these groups with tritiated borohydride. The total lung content of oxidized proteins recovered by bronchoalveolar lavage (BAL) was 0.3 +/- 0.07 nmol carbonyl.mL-1 BALF (mean +/- SEM) in the NS control group (n = 9) and tended to be increased, in the asymptomatic S group (n = 8; 0.59 +/- 0.14 nmol.mL-1). This parameter was significantly elevated both in IPF-NS (n = 14; 0.84 +/- 0.2 nmol carbonyl.mL-1 BALF) and SARC-NS (n = 15; 0.73 +/- 0.16 nmol.mL-1) as compared with the NS control. On the contrary, in smoking patients with IPF (n = 6; 0.41 +/- 0.1 nmol carbonyl.mL-1 BALF) and also in ASB-EXS (n = 6; 0.37 +/- 0.06 nmol.mL-1) it was not different from NS controls. The total amount of oxidized proteins correlated positively with the absolute number of eosinophils (EOS) in IPF-NS, IPF-S and SARC, and also with absolute polymorphonuclear neutrophil (PMN) numbers in IPF-NS and IPF-S. In conclusion, oxidative damage of BALF proteins occurred in nonsmoking patients with IPF and SARC. The amount of oxidized bronchoalveolar lavage fluid protein may provide a quantitative assessment of oxygen burden, a balance between oxidant stress and antioxidant defences.
Microheterogeneity of acute-phase glycoproteins in patients with pulmonary sarcoidosis
Authors: Hrycaj P , Wurm K , Mennet P , Muller W
Published: July 2003

This study was designed to investigate qualitative changes in the carbohydrate side-chains of two acute-phase glycoproteins, alpha 1-acid glycoprotein (AGP) and alpha 1-antichymotrypsin (ACT), in 37 patients with pulmonary sarcoidosis. The glycosylation profile of AGP and ACT was studied using affinity immunoelectrophoresis with the lectin concanavalin A (conA). Serum concentration of soluble receptor for interleukin-2 (sIL-2R) and activity of serum angiotensin converting enzyme (ACE) were measured by specific enzyme-linked immunosorbent assay (ELISA) and enzyme kinetic assay, respectively. Rocket immunoelectrophoresis and nephelometric assay were used to determine serum concentration of AGP, ACT and C-reactive protein (CRP). In 11 patients with active disease, a decreased reactivity of AGP with conA was found as compared with controls (n = 44) and patients with nonactive sarcoidosis (n = 26). A similar tendency was seen with ACT. In the same group, increased concentrations of serum AGP and higher levels of sIL-2R were detected compared with patients with nonactive sarcoidosis. In the entire sarcoidosis group, there was a negative correlation between ACE activity and AGP and ACT affinity for conA (r = -0.6358, and r = -0.5019, respectively) and a positive correlation with sIL-2R level (r = 0.8241). In nine patients with elevated concentrations of serum CRP, no differences were found in disease activity and glycosylation profile of AGP and ACT when compared to patients with normal serum CRP. The results suggest that in active pulmonary sarcoidosis changes in the glycosylation pattern of acute-phase glycoproteins exist, which are similar in trend and magnitude to those found in other chronic inflammatory diseases. The synthesis and glycosylation of acute-phase proteins in pulmonary sarcoidosis are probably regulated independently.
The repertoire of T-lymphocytes recovered by bronchoalveolar lavage from healthy nonsmokers
Authors: Burastero SE , Borgonovo B , Gaffi D , Frittoli E , Wack A , Rossi GA , Crimi E
Published: July 2003

We reasoned that persistent exposure to a limited set of airborne antigens could drive the preferential expansion of single T-cell clones in the lower respiratory tract of normal individuals. To explore this issue, the normal human alpha/beta T-cell receptor repertoire was studied in lung lymphocytes obtained by bronchoalveolar lavage (BAL) from the humen of the lower respiratory tract. BAL T-cells obtained from five healthy volunteers were first analysed using polymerase chain reaction to amplify all known V alpha and V beta genes of the T-cell receptor. T-cells from peripheral blood were used as an internal control. Heteroduplex analysis of the amplified products was then performed, to assess the clonal composition of the repertoire of lung- versus blood-derived T-lymphocytes within each amplified variable gene family. In all subjects, the T-cell repertoire in the lung was largely as heterogeneous as peripheral blood in terms of clonal composition. This indicated lack of preferential expansion of single T-cell clones. A few T-cell clones were simultaneously expanded in blood and lung in all individuals within a limited number of V beta (mean 2.4; range 2-4) and V alpha (mean 1.6; range 1-3) genes. We also found that lung T-lymphocytes expressed all of the V gene families of the T-cell receptor that were expressed by peripheral blood T-cells. Our results indicate that T-cell clones in the lower respiratory tract of normal individuals are distributed according to a largely polyclonal pattern, which corresponds to that found in peripheral blood.
Age-dependency of surfactant phospholipids and surfactant protein A in bronchoalveolar lavage fluid of children without bronchopulmonary disease
Authors: Ratjen F , Rehn B , Costabel U , Bruch J
Published: July 2003

Whilst alterations in surfactant components of bronchoalveolar lavage fluid (BALF) have been described in a variety of pulmonary diseases in adults, no information is available on the surfactant composition in children beyond the neonatal period. In order to obtain reference values for the paediatric age group, we have studied phospholipid profiles of BALF in children without pulmonary disease. The study population consisted of 38 children aged 3-15 yrs (mean +/- SD 8 +/- 4 yrs) undergoing elective surgery for nonpulmonary illnesses. Surfactant composition was analysed by high pressure liquid chromatography using both an ultraviolet and a light-scattering detector. Total phospholipid concentration was higher in children under 8 yrs of age and decreased with age. In contrast, the total protein concentration remained constant throughout the age range. No age-related changes in the relative composition of phospholipid fractions could be observed. Surfactant protein A concentrations were highly variable in all age groups. This study provides the first data on surfactant components in bronchoalveolar lavage fluid of healthy children and will be the basis for future studies of children with pulmonary diseases.
Pulmonary dysfunction in cystic fibrosis is associated with oxidative stress
Authors: Brown RK , Wyatt H , Price JF , Kelly FJ
Published: July 2003

The aim of this study was to determine whether a relationship exists between the circulating concentration of antioxidants, or markers of oxidative stress, and pulmonary function in cystic fibrosis patients. Plasma was obtained from 34 patients attending a cystic fibrosis clinic. Oxidative stress was investigated by measuring the concentrations of circulating lipid hydroperoxides and malondialdehyde (lipid peroxidation) and protein carbonyls (protein oxidation). Antioxidant status was determined from the plasma concentrations of alpha-tocopherol, ascorbic acid, uric acid and total sulphydryls. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and forced mid-expiratory flow (FEF25-75) were measured in 25 of the subjects by spirometry, and expressed as percentage predicted for normal height, weight and age. Lung function decreased significantly with age and was associated with decreased plasma alpha-tocopherol, ascorbic acid and sulphydryl concentrations. The reduction in pulmonary function correlated with elevated plasma malondialdehyde, but not with lipid hydroperoxide or protein carbonyl concentrations. Patients with severe lung dysfunction (FEV1 < 50% predicted) had higher plasma concentrations of lipid hydroperoxides than those with mild-to-moderate lung dysfunction (FEV1 > 50% pred). This study provides evidence that cystic fibrosis patients have inadequate antioxidant defences to cope with the elevated oxidative stress that they regularly experience. We believe that recurring oxidative lung injury contributes to the decline in pulmonary function in these patients.
Pulmonary function abnormalities in type I Gaucher disease
Authors: Kerem E , Elstein D , Abrahamov A , Bar Ziv Y , Hadas-Halpern I , Melzer E , Cahan C , Branski D , Zimran A
Published: July 2003

The purpose of this study was to determine the prevalence of pulmonary function and radiographic abnormalities among patients with type I Gaucher's disease, and to analyse the relationship between the pulmonary involvement and genotype and clinical severity score. All patients attending the Gaucher clinic at the Shaare Zedek Medical Center, Jerusalem, Israel, during the years 1992-1993 were prospectively evaluated. Each patient had pulmonary function tests, chest radiography, clinical assessment in terms of degree of organ involvement, and genotype analysis. Of the 95 patients included in the study (mean +/- SD age 29 +/- 15 yrs), 68% had some pulmonary function abnormalities, most commonly a reduced FRC and transfer coefficient for carbon monoxide (Kco), found in 45% and in 42% of the patients respectively. Total lung capacity (TLC) was reduced in 22% of the patients and forced expiratory flows in approximately one third of the patients. Signs of airtrapping (elevated residual volume (RV) or RV/TLC) were seen in 18% of the patients. Males had a higher incidence of reduced expiratory flow than females, (forced expiratory volume in one second (FEV1) was reduced in 36% of males vs 5% of females). Chest radiographic abnormalities were found in 17% of the patients, although only 4% had severe changes. Patients with abnormal pulmonary function had a significantly higher severity score index than those with normal pulmonary function tests. There was no association between abnormal pulmonary function and genotype or age. In conclusion, abnormal pulmonary function is common among type I Gaucher patients. Pulmonary function tests show airways obstruction, with reduced expiratory flows, reduction in lung volumes and alveolar-capillary diffusion abnormality. The rate of progression and the clinical significance need to be determined.
Human alveolar capillaries undergo angiogenesis in pulmonary veno-occlusive disease
Authors: Schraufnagel DE , Sekosan M , McGee T , Thakkar MB
Published: July 2003

The bronchial circulation undergoes angiogenesis in several pathological conditions, such as lung neoplasm and bronchiectasis, but whether the pulmonary circulation can do this has been questioned. A woman treated with mitomycin C and 5-fluorouracil developed progressive, fatal pulmonary hypertension over 5 months. In addition to light and transmission electron microscopic examination of her lung, her pulmonary vasculature was cast and the casts were studied with scanning electron microscopy. Light microscopy showed that she had pulmonary veno-occlusive disease and angiomatoid capillary growth in the alveolar walls. Transmission electron microscopy confirmed the presence of pulmonary hypertension and showed thickened endothelial basement membrane. Scanning electron microscopy of the cast blood vessels showed distortion and destruction of alveolar capillaries prohibiting the passage of erythrocytes. Large new capillaries developed on top of, and were connected to, the shrivelled capillaries that made up the alveolar wall. The new capillaries were larger and fewer, which reduced the alveolar-capillary interface. Arteries and veins were irregularly narrowed and the veins had broad muscularity. Oedema was present, and the pulmonary lymphatics were extensively cast, especially in the lobular septa, but the lymphatics had a normal appearance. It appears that this patient suffered extensive capillary damage and venous occlusion and that the response was extensive new capillary formation, sometimes in angiomatoid configurations, and hypertrophy of pulmonary veins and arteries. Casting the microvasculature and viewing it with scanning electron microscopy identified new alveolar capillaries in this patient with acquired pulmonary hypertension.
Contractile endothelin-B (ETB) receptors in human small bronchi
Authors: Adner M , Cardell LO , Sjoberg T , Ottosson A , Edvinsson L
Published: July 2003

Endothelins (ETs) are a family of novel regulatory peptides and various lines of evidence suggest an important role for ETs in regulating pulmonary function. Two receptors for endothelin, ETA and ETB, have been found in the human lung, and according to recent studies a non-ETA receptor seems to mediate the contraction of large sized human bronchi. Several studies have emphasized the importance of small bronchi in the pathogenesis of airway disease. In the present paper, improved methodology was used which enables in vitro studies of small human bronchi down to a diameter of 0.5-1.0 mm. Using the new methodology we have tried to further characterize this receptor. Small bronchi from the distal parts of the bronchial tree were obtained from pulmonary tissue removed from 15 patients with lung cancer. They were dissected and cut into ring segments, in which isometric tension was recorded. ET-1, ET-2 and ET-3 elicited strong concentration-dependent contractions of the human small bronchus. Basically, the three peptides were equipotent with about the same maximal response. Upon reapplication, they all showed the same tachyphylaxis pattern, reaching half the initial contraction. Comparative analysis of IRL 1620, a selective ETB receptor agonist, revealed that the effect of the ETB agonist was, in all respects, similar to the responses induced by the ETs. PD 145065, a combined ETA/ETB receptor antagonist competitively inhibited the contractions induced by IRL 1620, whereas FR139317, a selective ETA receptor antagonist, was without effect. In conclusion, the present study shows that accurate measurements can be made in vitro on small human bronchi and all present data are in favour of an ETB receptor mediating endothelin-induced contraction of human bronchi smaller than 1.0 mm.
The role of thrombosis in severe pulmonary hypertension
Authors: Chaouat A , Weitzenblum E , Higenbottam T
Published: July 2003

Considering the important surface in pulmonary circulation where blood can interact with the endothelium, the maintenance of blood fluidity through the lung, by antithrombotic pathways and products of the endothelium, is essential. This function appears to be ineffective in primary pulmonary hypertension and in severe secondary pulmonary hypertension. Thrombotic lesions are frequently found in pulmonary arteries in these diseases. Thrombin activity appears to be increased in severe pulmonary hypertension. Antithrombotic pathway disorders may account for this abnormality, particularly in chronic thromboembolic pulmonary hypertension and primary pulmonary hypertension. Injured endothelium, a constant feature in severe pulmonary hypertension, either primary or secondary, enhances thrombus formation in pulmonary vessels. This is probably related to thrombomodulin and tissue factor imbalance, impairment of prostacyclin and nitric oxide release, as well as inefficiency of fibrinolysis. Moreover, platelets appear to be activated in the pulmonary circulation of these patients. They release several mediators acting on vascular tone and as mitogenic agents, and may also contribute to thrombin and clot generation. Long-term oral anticoagulant and continuous infusion of prostacyclin, treatments which impede thrombosis, are known to improve the survival rate in patients with primary pulmonary hypertension. These are the strongest arguments, so far, in favour of the role of thrombosis in severe pulmonary hypertension. However, we do not know whether these abnormalities result from a previous vascular injury or represent the primary disturbance.
Enteral nutrition in patients with respiratory disease
Authors: Pingleton SK
Published: July 2003

Nutritional assessment and management is an important therapeutic modality in patients with respiratory disease. Malnutrition adversely affects respiratory function. Nutritional therapy for the spontaneously breathing patient should include an appropriate diet plus the consideration of nutritional supplements. Complete nutritional support should be undertaken with enteral nutrition in critically ill patients with respiratory failure. Nutritional complications occur. Overfeeding can lead to nutritionally associated hypercapnia.