[Lung function prediction equations in Tunisian children: taking into consideration pubertal stage]. / Equations prédictives des variables ventilatoires chez les enfants sains tunisiens : prise en considération du stade pubertaire.

OBJECTIVE: The purpose of this study was to set lung function prediction equations in Tunisian children with standing height and pubertal stage as the independent variables. METHODS: Spirometric values were measured with a Minato portable Spirometer in 684 asymptomatic Tunisian children (351 boys and 333 girls), 8 to 16 years of age. The specific parameters of pulmonary function that were measured included Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 second (FEV(1)), Peak Expiratory Flow (PEF), Maximal Expiratory Flow at 50% of the vital capacity (MEF(50)), and Maximum Mild Expiratory Flow between 25 and 75% (MMEF(25-75)). The pubertal status was assessed for males and females according to the Tanner method. RESULTS: A large variation was observed in the distribution of children's age and height by pubertal stages in both sexes. Multiple regression equations for FVC, FEV(1), MEF(50), MEF(25-75), and PEF for both sexes are presented with standing height and pubertal stage as the independent variables. CONCLUSION: The establishment of validated reference values relevant to the ethnic group of the local population should significantly improve medical surveillance of respiratory diseases in Tunisian children.

[Determining factors of pulmonary function in healthy Tunisian children]. / Déterminants de la fonction pulmonaire chez l'enfant sain en Tunisie.

Introduction Pulmonary function parameters are known to vary with age, sex, height and ethnic extraction. No normal values have been reported for pulmonary function in Tunisian children. Moreover, little attention has been paid to the factors affecting the development of lung function in Tunisian healthy children. State of art Birth weight and height, physical activity level, anthropometric, socioeconomic and environmental factors could influence the development of lung function in healthy children. Perspectives The studies conducted by our group have allowed us 1) to set reference values for spirometry in healthy Tunisian children; 2) to indicate that, in Tunisian adolescents, the use of only one morphological parameter such as height, is not sufficient, but the pubertal status could be taken into account to standardize the lung function and 3) to show the main predictive factors for pulmonary development to be the anthropometric factors such as height, weight, maximal inspiratory and expiratory thoracic perimeter, sex and age, and the environmental conditions (type of heating) in our population of healthy Tunisian children. Conclusion These findings should improve medical surveillance of respiratory diseases, stipulation of preventive and therapeutic measures in Tunisian children.

Factors affecting the development of lung function in Tunisian children.

We undertook to evaluate the impacts of morphology at birth, physical activity, anthropometric, socioeconomic and environmental factors on lung function in healthy Tunisian children. Pulmonary function parameters were measured with a Minato portable spirometer in a randomized population of 756 healthy children (388 males and 368 females) aged between 6 and 16. The morphology at birth, the gestational age, the physical activity, the socioeconomic status, the type of habitation, and the environmental factors were all assessed by a standard questionnaire. Using univariate analysis, we found that: (1) morphometric parameters (height, weight, maximal inspiratory, and expiratory perimeter), as well as sex were highly associated with pulmonary function parameters; (2) Height at birth showed strong significant relations with FVC, FEV(1), and FEV(1)/FVC; (3) lung function parameters were influenced by physical training of our children, socioeconomic status, indoor pollution, and passive smoking; and (4) we did not observe any association between the gestational age and the weight at their birth and lung function parameters. Using a general linear model analysis, morphometric parameters, age, sex, type of heating, and maximal inspiratory and expiratory perimeters had significant relation with respiratory parameters. In our population of healthy Tunisian children, the main predictive factors of the pulmonary development were the morphological factors such as height, weight, maximal inspiratory, and expiratory thoracic perimeter, sex and age, and the environmental conditions such as type of heating but not morphology at birth, physical activity, or socioeconomic status.

Spirometric values in Tunisian children: relationship with pubertal status.

BACKGROUND: Little is known about the effect of pubertal stages on lung function parameters in Tunisian children. AIM: The purpose of this study is to determine the relationship between lung function and pubertal stage in Tunisian children using anthropometric parameters. SUBJECTS AND METHODS: Pulmonary function parameters were measured with a Minato portable spirometer in 684 healthy Tunisian children (351 males and 333 females) aged between 8 and 16. The pubertal status was assessed for males and females according to the Tanner Method. RESULTS: A large variation was observed in the distribution of children's age and height by pubertal stages in both sexes. Height increased with age and pubertal stage in both males and females. The results also showed a significant increase in parameters of lung function (FVC, FEV(1), PEF, MEF(50) and MMEF(25-75)) with pubertal stage in Tunisian children. The analysis of covariance adjusting for anthropometric parameters showed that pubertal status had a significant independent effect on some pulmonary function parameters in both sexes. CONCLUSION: The results indicated that the parameters of pulmonary function for healthy Tunisian school children increased with age, height and pubertal stage. The present study has indicated that the use of only one morphological parameter such as height is not sufficient, but the pubertal status could be taken into account to standardize the lung function.

Carvedilol inhibits right ventricular hypertrophy induced by chronic hypobaric hypoxia.

Right ventricular hypertrophy induced by chronic hypoxia is mainly due to a mechanical stress upon the ventricular wall secondary to pulmonary arterial hypertension. However, the hypoxic chronic activation of the sympathetic nervous system can contribute to the development of right ventricular hypertrophy either via myocardial adrenergic receptors and/or a vasoconstriction and remodeling of pulmonary arteries. To highlight the specific role of the sympathetic nervous system on hypoxia-induced right ventricular hypertrophy and particularly the efficiency of carvedilol, our study compared physiological, myocardial, and pulmonary arterial morphometric data in rats treated by alpha-(prazosin), or beta-(propranolol) or alphabeta-(carvedilol) antagonist and exposed to chronic hypobaric hypoxia (2 weeks at 380 mmHg barometric pressure). In chronic hypoxia, both systolic right ventricular pressure and Fulton's ratio (right/(left+septum) ventricular weight) were lower in rats treated by prazosin (-16.7 and -13.6%), propranolol (-28.6 and -12.7%) and carvedilol (-15.9 and -14.3%) respectively when compared to glucose (p<0.05). Surprisingly, prazosin was unable to reduce right ventricular hypertrophy induced by chronic hypoxia, whereas, left ventricular weight increased. Wall thickness index of pulmonary arteries increased in chronic hypoxia and was reduced by carvedilol. In conclusion, the hypoxia-induced activation of the adrenergic system participates in the development of right ventricular hypertrophy. Carvedilol is effective in reducing hypoxia-induced right ventricular hypertrophy, pulmonary arterial hypertension, and muscularization of pulmonary arteries.

Characterisation of the ventilatory response to hypoxia in a model of transgenic anemic mice.

Both polycythemia and the increase in hypoxic ventilatory response (HVR) are considered as important factors of acclimatization to hypoxia. The objective of this study was to characterise the ventilation pattern at different inspired oxygen fraction in a model of chronic anemic mice. These mice have a targeted disruption in the 5' untranslated region of the Epo gene that reduces Epo expression such that the homozygous animal is severely anemic. Ventilation in normoxia in Epo-TAg(h) mice was significantly greater than in wild type, and the difference was mainly due to a higher tidal volume. HVR was higher in Epo-TAg(h) mice at every FIO2 suggesting a higher chemosensitivity. Resting oxygen consumption was maintained in anemic mice. Maximal oxygen consumption was 30% lower while hemoglobin was 60% lower in anemic mice compared to wild type. This small decrease in maximal oxygen consumption is probably due a greater cardiac output and/or a better tissue oxygen extraction and would allow these anemic mice to acclimatize to hypoxia in spite of low oxygen carrying capacity. In conclusion, Epo-TAg(h) anemic mice showed increased ventilation and hypoxic ventilatory response. However, whether these adaptations will contribute to acclimatization in chronic hypoxia remains to be determined.

Time course of ventilatory acclimatisation to hypoxia in a model of anemic transgenic mice.

We questioned the assumption that polycythemia is essential for adaptation to chronic hypoxia. Thus, the objective of our study was to determine if anemic Epo-TAg(h) mice could survive in hypoxia despite low oxygen carrying capacity. We explored the possibility that ventilatory acclimatisation is involved in the strategy used by anemic transgenic mice to adapt to chronic hypoxia. Epo-TAg(h) and Wild Type mice were exposed during 2 weeks at a barometric pressure of 450 Torr. After 1, 5 and 14 days of exposure, ventilation at different inspired oxygen fraction was measured in both groups. Ventilation during acclimatisation to hypoxia was significantly greater in Epo-TAg(h) than in Wild Type. The difference was mainly due to a higher tidal volume that could explain a higher arterial PO2 in Epo-TAg(h) mice. Epo-Tag(h) mice did not develop right ventricle hypertrophy after 2 weeks of exposure to hypoxia while Wild Type did. Hemoglobin concentration was 60% lower in anemic mice versus Wild Type after acclimatisation. In conclusion, ventilatory acclimatisation contributed to the adaptation of Epo-Tag(h) mice in chronic hypoxia despite low arterial oxygen carrying capacity.

Spirometric reference values in Tunisian children.

BACKGROUND: In Tunisia, there are no normal values of pulmonary function for healthy Tunisian children. OBJECTIVES: The purpose of this study was to set reference values for spirometric lung function in Tunisian children and to compare these results with other data sets. METHODS: Spirometric values were measured with a Minato portable spirometer in 1,114 asymptomatic, nonsmoking Tunisian children (581 boys and 533 girls) 6-16 years of age. Natural logarithmic values of lung function and standing height were used in the final regression model. RESULTS: Prediction equations for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV(1)), FEV(1)/FVC x 100, maximum mid expiratory flow (MMEF 25-75%) and peak expiratory flow (PEF) for both sexes are presented with standing height as the dependent variable. Our data show a significant increase in lung function with standing height in both sexes. Comparing our results with recent data, values of FVC and FEV(1) in both sexes in the present study are close to those in European, white US and Asian children, whereas our values are higher than the Libyan ones. CONCLUSIONS: Healthy Tunisian children showed similar spirometric reference values compared to European, white US and Asian children. Thus, these standards of lung function could also be used in Tunisia.

Carbon-monoxide poisoning in young drug addicts due to indoor use of a gasoline-powered generator.

We report six fatal cases of unintentional carbon-monoxide poisoning which occurred in a house occupied by young people. The source of carbon monoxide was a gasoline-powered generator. For all victims, an external body examination was carried out and blood and urine samples collected. Blood carboxyhaemoglobin (COHb) was performed using an automated visible spectrophotometric analysis. Blood-alcohol level quantification was performed using gas chromatography and drug screening in urine was performed by a one-step manual qualitative immunochromatography (Syva Rapid test, Behring Diagnostics Inc.) for benzoylecgonine (the main metabolite of cocaine in urine), morphine, 11-nor-Delta(9)-THC-9-COOH (cannabinoids) and d-methamphetamine. In all victims the COHb value was as high or higher than 65%. No alcohol was found in blood samples, but urine samples were positive for methamphetamine, cocaine and cannabis in five cases and for opiates in one case. In four victims, the urine sample was positive for at least three drugs. The availability and accuracy of rapid toxicological screening is an important tool for the medical examiner at the immediate scene of a clinical forensic examination.

Calcitonin gene-related peptide-immunoreactive nerves and neuroendocrine cells after lung transplantation in the rat.

Bronchial innervation is interrupted at lung transplantation. Nerve fibers with cell bodies above the section, such as sensory C fibers, should degenerate. Using histofluorescence, we evaluated calcitonin gene-related peptide (CGRP) immunoreactivity in syngeneic Lewis rats 1 and 5 mo after unilateral lung transplantation and in controls. CGRP-immunoreactive (IR) neuroendocrine cells were located within the epithelium of large and small bronchi. At 1 mo after transplantation, their number had significantly increased in large bronchi and had normalized 5 mo after transplantation. The density of CGRP-IR fibers in control lungs gradually decreased from large (0. 35 +/- 0.02 micron/micron basal lamina) to small (0.23 +/- 0.02) and peripheral bronchi (0.12 +/- 0.01). At 1 mo after lung transplantation, few CGRP-IR fibers were observed in large bronchi (0.17 +/- 0.02), fewer in small bronchi (0.04 +/- 0.01) (P < 0.01), and none in peripheral bronchi. At 5 mo after lung transplantation, transplanted lungs still had fewer CGRP-IR fibers in large (0.22 +/- 0.02) and small (0.11 +/- 0.02) bronchi (P < 0.02) than did controls, but there were, nonetheless, more in the small bronchi than at 1 mo after transplantation (P < 0.01). Additionally, few CGRP fibers were present in the peripheral bronchi (0.03 +/- 0.01) (P < 0.01). These results clearly demonstrate the occurrence of denervation followed by partial reinnervation with CGRP-IR fibers after transplantation in rat lung.

Phenotypic and quantitative changes in mast cells after syngeneic unilateral lung transplantation in the rat.

1. Lung transplantation causes a total interruption of the inneration and vascularization within the transplanted organ, followed by repair processes. This is frequently associated with bronchial hyper-responsiveness. A common feature of tissue repair is an increase in the number of mast cells. Three phenotypically distinct mast cell subsets, with respect to their protease content, have been identified in rat lung, and it is probable that mast cells of differing protease phenotype fulfil different functions. 2. We have compared the number, protease phenotype and distribution of mast cells in left lung from transplanted and control Lewis rats 1 month after syngeneic unilateral left lung transplantation, without interference of inflammation, graft rejection or of any treatment. Connective and mucosal-type mast cell phenotypes were characterized using antibodies directed against their specific rat mast cell proteases, RMCPI and RMCPII, respectively. 3. After transplantation, RMCPI and RMCPII tissue concentrations increased by 172% and 239%, respectively, compared with controls (13.1 +/- 1.2 and 5.6 +/- 1.0 micrograms/g). 4. Localization of mast cell phenotypes was studied by immunohistochemistry after double immunostaining. The number of mast cells increased after transplantation: the increase in the number of RMCPI-immunoreactive mast cells (RMCPI+) was significant around bronchioles and arterioles, around large vessels and in the pleura. The number of RMCPII+ mast cells also significantly increased around bronchioles and arterioles, as well as in the smooth muscle layer of large airways. Some mast cells stained for the presence of both RMCPI and RMCPII, supporting the existence of co-expressing phenotype in rat lung. The number of mast cells of the RMCPI+/II+ phenotype significantly increased around bronchioles and arterioles and in the pleura. Moreover, the distribution of the mast cell phenotypes was modified in the different areas after transplantation. 5. This indicates a local differentiation/maturation of mast cells after transplantation.

Do nasal mast cells release histamine on stimulation with substance P in allergic rhinitis?

The effects of nasal administration of increasing doses of exogenous substance P have been studied in patients with allergic rhinitis treated with placebo or with the H1 antagonist cetirizine (10 mg twice daily for 3 days). Responses to substance P were assessed by posterior rhinomanometry (measuring nasal airway resistance) and by measure of histamine, protein and albumin production and cell recovery in nasal lavage fluids before and after challenge. Substance P induced a dose-dependent increase in nasal airway resistance which was similar after treatment with either cetirizine or placebo (maximal increase in nasal airway resistance was 4.2-fold greater than the baseline with the placebo and 4.7-fold greater than the baseline with cetirizine). No histamine release was observed. Similar increases in protein and albumin production were observed after stimulation with substance P along with the placebo (protein: from 0.35 +/- 0.11 to 3.31 +/- 0.62 mg and albumin: from 0.09 +/- 0.04 to 2.08 +/- 0.39 mg) and when combined with cetirizine treatment (proteins: from 0.42 +/- 0.09 to 3.62 +/- 0.77 and albumin: from 0.17 +/- 0.04 to 2.19 +/- 0.51 mg). After stimulation with substance P, percentages of neutrophils recovered in nasal fluids increased from 26.2 +/- 11.5 to 54.5 +/- 9.5 with the placebo and from 35.5 +/- 11.0 to 53.6 +/- 9.5 with cetirizine. Eosinophils were inconsistently found after substance P stimulation during both treatments. In conclusion, nasal response to substance P is not modified by cetirizine which suggests that the effect of substance P is not secondary to histamine release in the nose in man.

In vitro bronchial hyperresponsiveness after lung transplantation in the rat.

In this study, we examined the effect of unilateral lung transplantation on in vitro responses of bronchial smooth muscle to electrical field stimulation (EFS) and exogenous acetylcholine (ACh). In syngeneic Lewis rats, we compared the contractile responses of the left hilar transplanted bronchus with that of the nontransplanted right bronchus and the left and right bronchi from control and sham-operated animals. Atropine-sensitive bronchial contraction to EFS was greater on left transplanted than on right nontransplanted bronchi at all frequencies and voltages used. In control and sham-operated animals, contractile responses to EFS were identical on left and right sides and similar to the responses of the right nontransplanted bronchus of the lung transplant recipient. Concentration-response curves to exogenous ACh were similar on transplanted and all control bronchi. Intramural cholinergic nerve cell bodies reactive for acetylcholinesterase were present in the transplanted bronchus. We conclude that EFS-induced cholinergic contraction of rat bronchial smooth muscle is enhanced after lung transplantation. Enhancement is not a result of medication, inflammation, or rejection, absent from our syngeneic transplant, or of upregulation of muscarinic post-junctional receptors because the response to exogenous ACh was normal. Hence, an increased release of ACh from cholinergic nerve terminals may occur, due either to hyperexcitability of postganglionic parasympathetic nerves or to loss of inhibitory mechanism resulting from interruption of neural connections with the central nervous system.

Is P50 the most representative P(SO2) to evaluate HbO2 affinity?

Off-line computer assistance allowed a correct visualization of the actual data included in any experimental whole oxygen-hemoglobin association curve. The affinity of hemoglobin for oxygen (characterized by the successive PO2 corresponding to any saturation value: P(SO2)), the shape of the association curve (Hill's curve and Hill's numbers) and the Bohr coefficients all along the oxygenation process, were determined with great accuracy. Results agreed with literature values obtained for successive steps of oxygenation. A batch of 78 computerized curves was divided into 3 groups (normal: NL, right deviated: RD and left deviated: LD) to which the principal component (P.C.) method was applied. It was therefore possible not only to study correlations between any curve summarized by its P.C. and any external variable but also to define for any association curve, whatever its eventual shift, the most representative value of P(SO2). For all mixed groups, the most significant parameter would be P44. If the characterization of the HbO2 dissociation curve is to be represented by a single point, then it should be P48 for the NL curves, P52 for the LD group, and P24 for the RD group. Then, the common use of P50 appeared to be illegitimate and inadequate for the right shifted curves, a very frequent circumstance in clinical practice.

Application of new calculation algorithms to oxygenation parameters of cirrhotic patients. A comparison between calculated and measured data.

Oxygen status from both arterial and mixed venous blood was analyzed by reliable methods in 39 cirrhotic patients. These measured data were checked with computed oxygen parameters by new calculation algorithms. Calculated oxygen contents were higher than directly measured values but there was a highly significant correlation between them. Calculated and measured 2,3-DPG mean values were not significantly different but there was no correlation between them. A large difference was observed between measured and computed evaluation of oxygen-hemoglobin affinity without correlation between P50. In hyperkinetic patients, no correlation was observed between 'compensation factor' and the increase of cardiac index. So, in these patients the new iterative equations were not valid to determine traditional oxygen parameters from only Po2 and So2 arterial measurements. Moreover the new oxygenation parameters appeared frankly inadequate.

Lung function of children treated for malignant extrapulmonary tumors.

Lung function was studied in 29 children suffering from extrapulmonary tumors of varying etiology (Wilm's tumor, n = 7; bone malignancy, n = 17; nasopharyngeal epithelioma, n = 5). Lung volume: vital capacity (VC) and functional residual capacity (FRC), lung mechanics: lung resistance (RL), dynamic lung compliance (CLdyn) and static lung compliance (CLstat) and lung transfer factor for CO (TLCO), and blood gases were determined at different stages of therapy: at t0, before any aggressive treatment for respiratory function; at t1, after the initiation of polychemotherapy with or without local tumoral treatment (surgery or local irradiation); at t2, less than 6 months after onset of thoracopulmonary irradiation (whole lung irradiation at 20 grays) (group I), or local thoracopulmonary irradiation at high exposure greater than 40 grays (group II); at t3 after more than 6 months following irradiation with chemotherapy maintained; at t4, after cessation of all treatment (mean: 25 months +/- 14 after cessation of treatment). At t0, lung function data in children without pulmonary metastases did not deviate from predicted values. At t1, group I showed a significant decrease in CLdyn, which could be due to chemotherapy and for 5 children to consequences of abdominal surgery. In group II, only two children had a low CLdyn and also a significant decrease in VC (possibly due to the site of the tumor). After irradiation (at t2), FRC, TLCO and CLdyn were significantly lower than the predicted values and lower than at t1 in both groups (p greater than 0.01). At t3, functional parameters did not show any change compared to t2. At t4, FRC and TLCO were within normal limits in both groups but CLdyn, CLstat and the CLdyn/FRC ratio remained significantly decreased. It is suggested that these functional abnormalities are due to inadequate alveolar growth.

Lung mechanics and breathing pattern during wakefulness and sleep in children with enlarged tonsils.

Thirteen children (mean age, 45 months) with nocturnal symptoms of upper airway obstruction, the result of enlarged tonsils, were tested during wakefulness (W) and sleep (S) induced by chloral hydrate (less than or equal to 50 mg/kg). During W, lung mechanics, blood gas, breathing pattern, and airflows during tidal breathing were in the normal range. During S, total lung resistance increased significantly, and dynamic lung compliance and transcutaneous PO2 decreased significantly. During S, the tidal volume (VT) and the mean inspiratory flow, normalized for body weight (BW), decreased whereas the ratio of the inspiratory time (TI) over the total duration of the respiratory cycle (TTOT) rose, indicating a longer contraction time of the respiratory muscles. The time to reach peak inspiratory flow, measured as a percentage of TI (dTI/TI), increased in seven children, with no change in the ratio of the expiratory flow over the inspiratory flow, both measured at 50% of VT (EF50/IF50). In three other patients dTI/TI decreased with an increase in EF50/IF50. We conclude that in children with enlarged tonsils, S modified lung mechanics, gas exchange, and the inspiratory components of the breathing pattern and airflow.

Occlusion pressure and breathing pattern in healthy children.

The breathing pattern was investigated in 62 children aged 4 to 16 years together with the mouth pressure generated 0.1 s after an occlusion at the endexpiratory level (P0.1). A group of 20 adults (18 to 32 years old) were tested in a similar way. The values of P0.1 obtained during room air breathing at rest in the children decreased with age as a power function P0.1 = 8.51 A-0.62 (where A is age in years), r = -0.74. Adult values of P0.1 were achieved at about 13 years. After O2 inhalation P0.1 decreased in children, but the changes in P0.1 were independent of age. Respiratory frequency decreased with age while inspiratory time (TI) increased, both reaching adult values at about 13 years. The ratio of TI over the total respiratory cycle duration did not change significantly with age in the entire population. The absolute value of tidal volume (VT) increased with age, but not when normalized for body weight (BW). The mean inspiratory flow (VT/TI) normalized for BW decreased with age in children as did P0.1. There was a significant relationship between P0.1 and VT/TI normalized for body weight (r = 0.63).