Body plethysmography--its principles and clinical use

Body plethysmography allows to assess functional residual capacity (FRC(pleth)) and specific airway resistance (sRaw) as primary measures. In combination with deep expirations and inspirations, total lung capacity (TLC) and residual volume (RV) can be determined. Airway resistance (Raw) is calculated as the ratio of sRaw to FRC(pleth). Raw is a measure of airway obstruction and indicates the alveolar pressure needed to establish a flow rate of 1 L s(-1). In contrast, sRaw can be interpreted as the work to be performed by volume displacement to establish this flow rate. These measures represent different functional aspects and should both be considered. The measurement relies on the fact that generation of airflow needs generation of pressure. Pressure generation means that a mass of air is compressed or decompressed relative to its equilibrium volume. This difference is called "shift volume". As the body box is sealed and has rigid walls, its free volume experiences the same, mirror image-like shift volume as the lung. This shift volume can be measured via the variation of box pressure. The relationship between shift volume and alveolar pressure is assessed in a shutter maneuver, by identifying mouth and alveolar pressure under zero-flow conditions. These variables are combined to obtain FRC(pleth), sRaw and Raw. This presentation aims at providing the reader with a thorough and precise but non-technical understanding of the working principle of body plethysmography. It also aims at showing that this method yields significant additional information compared to spirometry and even bears a potential for further development.     

Chloroquine prophylaxis, iron/folic-acid supplementation or case management of malaria attacks in primigravidae in western Uganda: effects on congenital malaria and infant haemoglobin concentrations

A randomized, double-blind, placebo-controlled trial, which compared the effects of three interventions (weekly chloroquine prophylaxis, daily iron and weekly folic-acid supplementation, and case management of malaria) on congenital malaria, maternal haemoglobin (Hb) and foetal outcome, was conducted among primigravidae resident in Hoima district, Uganda. Among 473 babies examined at birth or within 7 days of birth, 198 (42%) were parasitaemic, the level of parasitaemia in an infant being strongly correlated with those of placental (P< 0.01) and maternal, peripheral parasitaemia (P < 0.01). However, 33 (17%) of the parasitaemic babies were born to mothers who had placental but not peripheral parasitaemia, 22 (11%) to mothers who had peripheral but not placental parasitaemia, and 12 (6%) to mothers with neither peripheral nor placental parasitaemia. Overall, 163 babies were each examined for malarial parasites at birth and 1 month later. Of the 76 (47%) found to have parasitaemia at birth, 37 (23%) appeared aparasitaemic at the 1-month follow-up but 28 (17%) were still parasitaemic at that time. Among the babies born to the mothers who only received case management of malaria during pregnancy, parasitaemia at birth was associated with infant anaemia at birth (i.e. < 140 g Hb/litre; P = 0.03). Infants found to be parasitaemic at the 1-month follow-up had lower mean concentrations of Hb at that time than their aparasitaemic counterparts (P= 0.03). Parasitaemia at birth was not significantly associated with low birthweight, in any of three intervention groups. The intervention given to the mother had no significant effect on the parasitaemia of her baby, either at birth or at the age of 1 month. Congenital malaria per se may have little influence on birthweight but may have an impact on infant anaemia. In conclusion, congenital parasitaemia was not associated with birthweight, but was related to anaemia at birth in infants born to women who had only received active case management during their pregnancies.     

Acute protection against exercise-induced bronchoconstriction by formoterol, salmeterol and terbutaline.

The onset of bronchoprotection as obtained by various beta2-agonists has not been examined in a comparitive study. In this study, the onset of bronchodilation and protection against exercise-induced bronchoconstriction in asthmatics after inhalation of the long-acting beta2-agonists formoterol and salmeterol and the short-acting beta2-agonist terbutaline were measured. Twenty-five subjects with asthma and a history of exercise-induced bronchoconstriction (mean baseline forced expiratory volume in one second (FEV1): 90% predicted; mean fall in FEV1 after exercise: 31% from baseline) were enrolled in this double-blind, double-dummy, placebo-controlled, randomized, four-period crossover study. Exercise challenges were performed on 12 days at either 5, 30, or 60 min after inhalation of a single dose of formoterol (12 microg Turbuhaler), salmeterol (50 microg Diskus), terbutaline (500 microg Turbuhaler) or placebo. Exercise-induced bronchoconstriction (maximum fall in FEV1 or area under the curve) did not differ significantly between terbutaline, formorerol and salmeterol either 5, 30, or 60 min after inhalation of the study medication. In contrast, the onset of bronchodilation was slower after salmeterol compared to terbutaline and formoterol (p<0.05, each), which both showed a similar time course. At all time points between 5 and 60 min, formoterol provided significantly greater bronchodilation than salmeterol (p<0.05). These data indicate that equipotent doses of the bronchodilators salmeterol, formoterol and terbutaline were similarly effective with respect to their short-term protective potency against exercise-induced bronchoconstriction, despite the fact that the time course of bronchodilation was significantly different between the three beta2-agonists.     

Flow cytometric analysis of the effect of dithiothreitol on leukocyte surface markers.

Pretreatment with dithiothreitol (DTT) is necessary to dissolve mucus in samples of induced sputum prior to analysis. However, DTT may affect cell surface markers which are essential for lymphocyte subtyping. Therefore, the aim of this study was to evaluate the effect of DTT on an appropriate panel of surface markers. Peripheral blood leukocytes were used because these cells, in contrast to sputum cells, could be obtained without DTT treatment. Peripheral blood from healthy donors was incubated with either DTT according to standard sputum procedures or phosphate-buffered saline (PBS), washed and incubated with fluorochrome-labelled antibodies. After lysis of erythrocytes, analysis was performed using a calibrated flow cytometer. Leukocyte populations were identified by their light scattering properties. For analysis, fluorescence intensity was compared between DTT- and PBS-treated samples. After treatment with DTT, fluorescence intensity was significantly increased in CD16-positive granulocytes; it was reduced in CD2-positive lymphocytes, CD45-positive lymphocytes and CD14-positive monocytes (p < or = 0.001). These changes occurred in all samples. The fluorescence intensity of CD3-, CD4-, CD8-, CD19-, CD56- and histocompatibility leukocyte antigen DR-positive lymphocytes was not altered by DTT. However, there were statistically significant (p<0.001), although small, changes in the percentages of leukocytes. The present data demonstrate that, although dithiothreitol as used in sputum analysis affects some surface markers of peripheral blood leukocytes, comparability between samples concerning lymphocyte surface markers is preserved. Therefore, it is suggested that treatment of sputum samples with dithiothreitol does not invalidate the immunocytochemical analysis of lymphocytes.     

The effect of repeated ozone exposures on inflammatory markers in bronchoalveolar lavage fluid and mucosal biopsies

The aim of this study was to investigate the cellular and biochemical events associated with repeated exposures to ozone. Twenty-three healthy subjects underwent single exposures to 200 ppb ozone and to filtered air (FA), as well as repeated exposures to 200 ppb ozone on 4 consecutive days, each for 4 h of intermittent exercise. Bronchoalveolar lavage was performed and mucosal biopsies were taken 20 h after the single or the last of the repeated exposures. As compared with FA, the single exposure to ozone caused a decrease in FEV(1), an increase in the percentages of neutrophils and lymphocytes, the concentrations of total protein, IL-6, IL-8, reduced glutathione, urate, and ortho-tyrosine in BAL fluid (BALF), but no changes in the cellular composition of biopsy. After the repeated exposure, the effect on lung function was abolished and differential cell counts in BALF were not significantly different from those after FA. However, the concentrations of total protein, IL-6, IL-8, reduced glutathione, and ortho-tyrosine were still increased. IL-10 could only be detected in BALF after repeated ozone exposures. Furthermore, macroscopic scores for bronchitis, erythema, and hypervulnerability of airway mucosa were increased, as well as numbers of neutrophils in bronchial mucosal biopsies. Our data demonstrate that airway inflammation persists after repeated ozone exposure, despite attenuation of some inflammatory markers in BALF and adaptation of lung function.     

Bancroftian filariasis infection,disease, and specific antibody response patterns in a high and a low endemicity community in East Africa

Bancroftian filariasis infection, disease and specific antibody response patterns in a high and a low endemicity community in East Africa were analyzed and compared to assess the relationship between these parameters and community transmission intensity. Overall prevalences of microfilaremia and circulating filarial antigenemia were 24.9% and 52.2% in the high and 2.7% and 16.5% in the low endemicity community, respectively. A positive history of acute attacks of adenolymphangitis was given by 12.2% and 7.1% of the populations, 4.0% and 0.9% of the adult (> or = 20 years old) individuals presented with limb lymphedema, and 25.3% and 5.3% of the adult males had hydrocele, in the high and the low endemicity community, respectively. Both infection and disease appeared earlier and reached much higher levels in the high than in the low endemicity community. The observed overall and age-specific infection and disease patterns in the two communities were in agreement with the view that these are primarily shaped by transmission intensity. No statistically significant relationships between infection status of fathers and mothers and that of their children were observed in any of the communities for either microfilaremia or for circulating filarial antigenemia. The overall levels (prevalence and geometric mean intensity) of filarial-specific IgG1, IgG2, IgG4, and IgE were significantly higher in the high endemicity community than in the low endemicity dommunity. Surprisingly, the opposite pattern was found for IgG3. Community transmission intensity thus appears to be an important determinant of observed inter-community variation in infection, disease, and host response patterns in Bancroftian filariasis.     

Dose reduction of inhaled corticosteroids under concomitant medication with montelukast in patients with asthma.

The present study aimed at comparing the effects of a dose reduction of inhaled corticosteroids on lung function, indirect measures of airway inflammation and clinical scores during treatment with a leucotriene receptor antagonist. In 50 patients (mean forced expiratory volume in one second (FEV1) 94% predicted), steroid doses (800 microg beclomethasone dipropionate) were first reduced to 50% and then to 25%, for 6 weeks each. One group received a placebo and the other group received montelukast (10 mg). The first reduction did not cause significant effects. During the second, FEV1 and peak expiratory flow decreased in both groups (p<0.001). Daytime symptoms were not altered with placebo but were reduced by montelukast (p<0.05). Night-time symptoms were slightly elevated with placebo (p<0.05) but not montelukast, as well as the use of supplemental salbutamol. Changes in provocative concentration of methacholine causing a 20% fall in FEV1 (PC20), sputum eosinophils and exhaled nitric oxide were mostly nonsignificant for both placebo and montelukast. These data demonstrate that a 75% reduction in the dose of steroid given to patients with asthma led to a deterioration in lung function not prevented by montelukast, whereas changes in clinical state seemed to favour montelukast treatment. It therefore appears that potential effects of montelukast, in the presence of low-dose steroids, could not be attributed to single indices of lung function or airway inflammation.     

Micronutrient status indicators in individuals single- or double-infected with HIV and Wuchereria bancrofti before and after DEC treatment

Objective  To identify possible associations between selected micronutrient status indicators (serum ferritin, retinol, β-carotene, α-tocopherol, and the acute phase reactant α-1 antichymotrypsin) and infection with human immunodeficiency virus (HIV) or Wuchereria bancrofti , and to assess the effect of the antifilarial drug diethylcarbamazine (DEC) on the micronutrient status indicators in individuals positive for one or both of the two infections.
Methods  Serum concentrations of ferritin, retinol, β-carotene, α-tocopherol and the acute phase reactant α-1 antichymotrypsin were examined in 59 individuals with HIV, W. bancrofti infection, or both, in Tanga Region, Tanzania, before and 12 weeks after treatment with DEC.
Results  HIV infection, but not W. bancrofti infection, was associated with higher serum ferritin concentrations and lower β-carotene and α-tocopherol. Neither HIV infection nor W. bancrofti infection was associated with serum retinol. The four micronutrient status indicators and α-1 antichymotrypsin were generally lower at 12 weeks after treatment both in the DEC and the placebo groups.
Conclusions  The negative association between HIV infection and the antioxidant vitamins β-carotene and α-tocopherol may be due to infection-induced oxidative stress, whereas W. bancrofti infection seemed not to be associated with oxidative stress. The drop in antioxidant vitamin concentrations after treatment may be due to oxidative stress induced by HIV progression (HIV infected) and inflammation around dead adult worms and microfilariae ( W. bancrofti infected) rather than to an effect of DEC.