A pharmacokinetic evaluation of the second-generation H1-receptor antagonist cetirizine in very young children.

The pharmacokinetics of the second-generation H1-receptor antagonist cetirizine was studied in eight children younger than 4 years of age who were treated with a single dose of cetirizine solution (5 mg). These children were hospitalized with suspected allergic respiratory problems or recurrent respiratory tract infections. Blood samples were collected at 1/2, 1, 1 1/2, 2, 4, 6, 8, 12, and 24 hours, and a 24-hour urine collection was performed in five of the samples. The findings obtained in children were compared with those obtained in 16 healthy young adults (mean +/- SD, 24.6 +/- 4.1 years) who received a single 20 mg dose. Cetirizine was absorbed more slowly in children (p = 0.006; mean +/- SD, 1.44 +/- 1.12 hours) than in adults (0.62 +/- 0.22 hours). The plasma elimination half-life of cetirizine was significantly shorter in children (p < 0.001; 4.91 +/- 0.6 hours) than in adults (8.6 +/- 2.1 hours), and the clearance rate was significantly higher in children (p < 0.001; 1.48 +/- 0.41 ml/min/kg) than in adults (0.80 +/- 0.17 ml/min/kg). Urinary excretion of unchanged cetirizine was significantly lower in children (p < 0.001; 37.8% +/- 5.2%; n = 5) than in adults (57.7% +/- 11.8%). Therefore the metabolism of cetirizine is faster in young children than in adults. This effect must be taken into account in future pharmacodynamic studies in this age group.

Pharmacokinetics and pharmacodynamics of cetirizine in infants and toddlers.

The pharmacokinetics of the second generation H1-receptor antagonist cetirizine were studied in 15 infants and toddlers (mean +/- SD age, 12.3 +/- 5.4 months) who were treated with a single 0.25 mg/kg dose of cetirizine solution. The infants and toddlers were hospitalized for recurrent respiratory infections or other hypersensitivity-related diseases. Blood samples were collected at 1/2, 1, 11/2, 2, 4, 6, 8, 12, and 24 hours, and a 24-hour urine sample was obtained. A peak plasma level of 390 +/- 135 ng/ml was observed after 2.0 +/- 1.3 hours. The elimination half-life was 3.1 +/- 1.8 hours, the apparent oral body clearance was 2.13 +/- 1.15 ml/min/kg, and the apparent volume of distribution was 0.44 +/- 0.19 L/kg. The excretion of unchanged cetirizine in six complete urinary collections was 62.7% +/- 13.2% of the administered dose. An additional pharmacodynamic study (inhibition of the histamine-induced wheal and flare) was performed in 10 of these infants and toddlers, after the intake of 0.25 mg/kg cetirizine twice a day for at least 4 days. A 90% +/- 12% inhibition of the wheal and a 87% +/- 17% inhibition of the flare were still observed 12 hours after the last intake. The duration of the H1-inhibition by cetirizine at the cutaneous level is thus longer in infants and toddlers than could be inferred from its pharmacokinetics; the level of inhibition at 12 hours was the same as in older age groups.

Genetic deficiency of C4 presenting with recurrent infections and a SLE-like disease. Genetic and immunologic studies.

A young girl presenting with recurrent pulmonary infections and atypical lupus erythematosus was totally deficient in C4. In one sister, also deficient in C4, the same symptoms developed. Results of family studies were consistent with an autosomal recessive mode of transmission and with linkage of the genes determining C4 deficiency to those of the major histocompatibility complex. The patient's serum and red cells were Chido- and Rodgers-negative. Humoral and cellular immunity were normal, except for a low lymphocyte response in mixed lymphocyte culture. The cellular function of the patient's polymorphonuclear leukocytes was normal, for both phagocytosis and bactericidal activity using Candida albicans. However, in the presence of C4-deficient serum, opsonin generation and bactericidal indexes were diminished. These defects were completely reversible upon addition of purified C4.

Critical evaluation of lung scintigraphy in cystic fibrosis: study of 113 patients.

A long-term study has been performed on 285 lung perfusion scintigrams obtained from 113 patients with cystic fibrosis. Transverse and longitudinal comparisons with clinical and radiological scores, as well as retrospective analysis of the deceased patients, were the methods used in order to evaluate the importance of the scintigraphic images. It appears that lung scintigraphy is the best index of the regional lung impairment, and contributes, as does a chest radiograph, to the early detection of lung lesions, the two methods being complementary. The survival rate of CF patients reached 0.80 at 9 yr when initial scintigraphy was normal or only moderately impaired, but fell to 0.18 when severe lesions were seen on the first scintigrams.

Successful management of recurrent pneumothorax in cystic fibrosis by localized apical thoracoscopic talc poudrage.

Thoracoscopic talc poudrage of the entire pleural surface constitutes successful treatment of recurrent pneumothorax in cystic fibrosis (CF); however, subsequent lung transplantation is seriously jeopardized due to the development of extensive pleural adhesions. We describe a 27-year-old patient with CF with recurrent right-sided pneumothorax, refractory to chest tube drainage and to chemical (tetracycline) pleurodesis, who was successfully treated with a localized, apical thoracoscopic talc poudrage, thereby preserving the possibility of subsequent lung transplantation.

Plasma insulin-like growth factor-I determinations in patients with cystic fibrosis: Influence of the nutritional and liver status.

Insulin-like growth factor-1 (Igf1), a useful and early marker of undernutrition in inflammatory diseases, is dependent on the calorie and protein content of the diet. In 31 children and adolescents with cystic fibrosis (CF), a chronic inflammatory disease, the influence of the degree of liver dysfunction and the protein and calorie content of the diet on the circulating Igf1 was evaluated. No significant difference in the median plasma Igf1 concentration, measured by RIA, between the CF children (0.80 U/ml) and a for age and puberty matched control group (0.61 U/ml) was found. Expressing the Igf1 concentration as a percentage of normal for age, gave for the CF patients with liver involvement a lower level (median: 76%) than in those without (median: 101%). No correlation existed between the circulating Igf1 levels and the body height SDS, the body weight index and the calorie or protein intake of the patients.

Acute effects of oxygen, nifedipine, and diltiazem in patients with cystic fibrosis and mild pulmonary hypertension.

The acute effects of oxygen, nifedipine, and diltiazem were studied in eight patients with cystic fibrosis and mild pulmonary hypertension, to assess the possibility of relieving the latter before the occurrence of irreversible vascular changes. Oxygen decreased pulmonary pressure (-23%) and resistance (-21%), while increasing systemic resistance (+23%). Nifedipine increased cardiac index (+30%), at the expense of augmented right ventricular work (+42%), resulting in a decreased calculated pulmonary resistance (-23%); pulmonary artery pressure remained unchanged, however. Nifedipine decreased arterial Po2 (-10%), suggesting ventilation-perfusion mismatch. Four of the eight patients responded to diltiazem. Their pulmonary pressure (-35%) and resistance (-43%) decreased, while systemic vascular tone remained unchanged. Oxygen in three patients, and diltiazem in two, returned pulmonary pressures and resistances to normal values. Early reversal of pulmonary hypertension is possible, and intervention is desirable before the establishment of chronic hypoxia, cor pulmonale, or right ventricular failure. Our data does not support the use of nifedipine in pulmonary hypertension, but shows that oxygen, and in some cases diltiazem, act as effective and selective pulmonary vasodilators.

Endoscopic unroofing of a bronchogenic cyst.

Flexible fiberoptic bronchoscopy (FFB) has become common practice for pediatric pulmonologists, allowing easier detection of certain abnormalities at an earlier stage. We report the endoscopic diagnosis of a large mediastinal bronchogenic cyst and its successful endoscopic unroofing in a symptomatic baby.

Differential cytology of bronchoalveolar lavage fluid in asthmatic children.

Although asthma usually begins in childhood, limited information is available as to the inflammatory reaction of asthmatic children compared to adults and the influence of age. We investigated the cytology of bronchoalveolar lavage fluid (BALF) in 39 newly diagnosed wheezy children (minimum of 3 wheezing episodes during last 6 months): 21 allergic and 18 nonallergic subjects. None had received antiinflammatory treatment. Bronchoalveolar lavage (BAL) was performed, instilling 0.5 ml.kg(-1) body weight of warmed saline in 4 successive fractions. The first 2 aliquots (BALF 1) were pooled for microbiology and cytology, and the last 2 (BALF 2) for cytology only. Recovery correlated inversely with age, the most significant being for BALF 2 (r = -0.52, P = 0.001). Children under 2 years of age had larger amounts of ciliated columnar and goblet cells (P = 0.0074). Other cell types did not show age dependency. Differential cytology was characterized by a high number of creola bodies, bronchial epithelial cells (M = 68 x 10(3).ml(-1), R = 5-349), and neutrophils (M = 92 x 10(3).ml(-1), R = 0-1,257). Eosinophils were the only cells distinguishing allergic from nonallergic subjects (P = 0.003). The 16 children with positive microbiology had more neutrophils than the noninfected (P = 0.008), the latter still having more neutrophils than found in adults. These data suggest a limited age dependency in BALF cytology. Differential cytology in BALF might be helpful in differentiating asthma in children. Neutrophil inflammation might be more important than in adults.

Determination of right ventricular ejection fraction in children with cystic fibrosis.

The radionuclide right ventricular ejection fraction (RVEF) determined by means of Krypton-81m represents a simple, noninvasive, and accurate procedure to quantify the right ventricular contractility. This procedure was applied to 25 young patients with cystic fibrosis. The RVEF tended to decrease with the progression of the lung disease, as assessed by the clinical S-K score, the degree of the defects on lung scintigraphy, the PaO2, and the lung function tests. However, the decrease of RVEF in patients with marked lung function tests. However, the decrease of RVEF in patients with marked lung involvement was moderate, and terminal lung disease was sometimes associated with normal right heart contractility.

Gastroesophageal reflux and unexplained chronic respiratory disease in infants and children.

Thirty-eight children, aged from a few weeks to 7 years, with severe chronic pulmonary disease and without gastrointestinal symptoms, were investigated for gastroesophageal reflux (GER), using prolonged pH probe monitoring and gastroesophageal scintiscanning. All treatments were discontinued before testing. GER was found in 24 patients (63%) (group I) and it was not observed in 14 patients (group II). All patients of group I received antireflux treatment, consisting of cisapride; in 22 of 24 patients, GER was controlled, as indicated by improvement of either pH monitoring or scintiscanning, or both. Eighteen of these 22 (82%) had remission of their pulmonary disease, and only two patients of group II (14%) had spontaneous remission of the respiratory symptoms. We concluded that GER was probably the cause of the respiratory disease in 63% of our patients, since treatment of GER was followed by disappearance of the respiratory complaints in most of them. The combination of gastroesophageal scintiscanning and pH probe study improved the diagnostic accuracy.

Left ventricular perfusion deficit in patients with cystic fibrosis.

Left ventricular failure is not considered an important feature in cystic fibrosis (CF), but abnormalities of left ventricular function have been reported. Except for a few cases of heart failure in neonates with CF, there is no evidence of a primary disorder of the myocardium in patients with CF. Since left ventricular perfusion disturbances can cause left ventricular dysfunction, we decided to investigate left ventricular perfusion during exercise using sestamibi-Tc-99m-labeled macroaggregates. Eighteen CF patients with varying degrees of disease severity participated in the study. They underwent a thorough clinical evaluation, lung perfusion scan, pulmonary function testing, echocardiography, transcutaneous measurement of oxygen saturation at rest and during exercise, and an exercise test with injection of sestamibi-Tc-99m-labeled macroaggregates at peak exercise. Six patients (33%) showed abnormalities of the myocardial distribution of sestamibi-Tc-99m-labeled macroaggregates during exercise. Scanning abnormalities correlated with the clinical score, mean maximum expiratory flow at 50% of vital capacity (MEF50), and arterial oxygen desaturation during exercise. We conclude that deficits in left ventricular uptake of sestamibi-Tc-99m-labeled macroaggregates during exercise seem common in patients with severe CF lung disease. The cause of these deficits is not fully understood, but the occurrence seems to be associated with a poor prognosis.

Thoracoscopic T2-T3 sympathicolysis for essential hyperhidrosis in childhood: effects on pulmonary function.

Thoracoscopic T2-T3 sympathicolysis (TS) is a minimally invasive treatment for patients suffering from severe, refractory essential hyperhidrosis (EH). TS has previously been shown to be safe and efficacious in children. In order to examine the effects of TS on respiratory function, pulmonary function tests (PFT) were performed prior to and 6 weeks and 6 months after TS in 12 children with EH (3 boys; mean age 12.8+/-2.5 years). Small asymptomatic decreases in forced expiratory volume in one second (FEV1; -2%), forced expiratory flow after expiration of 75% of vital capacity (FEF75; -9.6%), total lung capacity (TLC; -1%), transfer factor for diffusion of carbon monoxide (T(LCO); -7.6%), and transfer coefficient for diffusion of carbon monoxide (K(CO); -1.5%) were observed 6 weeks after TS. These changes are comparable to those observed in adults but did not reach statistical significance in small children. In line with observations in adults, TLC (and T(L,CO)) returned to baseline values 6 months after TS, whereas FEV1, FEF75, and K(CO) remained at their 6-week level. In conclusion, TS causes only small, statistically insignificant, and asymptomatic decreases in pulmonary function in children. TS can, therefore, be considered a safe treatment option in children suffering from severe, refractory EH.

Unusual ventilation-perfusion patterns in primary lung tuberculosis.

We report two cases of primary lung tuberculosis in children with unusual perfusion ventilation scintigraphic patterns. In the first case, a mismatch in the right upper lobe suggests an elective compression of the bronchi by the mediastinal lymph nodes; in the second case, the total absence of ventilation and perfusion of the left lobe at scintigraphy illustrates the discrepancy sometimes encountered between chest x-ray and lung scintigraphy.

Pathological changes of the lateral nasal wall in patients with cystic fibrosis (mucoviscidosis).

In a prospective clinical study, 84 patients aged 3 months to 34 years (mean age: 12 years; 53 males and 31 females), with cystic fibrosis systematically underwent an ENT examination, including rigid endoscopy of the anterior nasal cavity and lateral nasal wall. In 28 cases, CT-scan of the sinuses was performed. Mucopyosinusitis of the maxillary sinus with medial projection of the inter-naso-sinusal wall was present in 10 children (12%, mean age: 4 years; range: 3 months to 8 years). Nasal polyposis was present in 37 patients (45%) from the age of 5 years on (mean age: 15 years). Nasal obstruction was the main complaint when the condition was severe. The routine use of the endoscope makes it possible to diagnose early pathological changes of the lateral nasal wall. Local treatment could then help slow down progress evolution toward a more massive involvement.

Congenital stridor in infancy. Clinical lessons derived from a survey of 31 instances.

Thirty-one cases of persistent stridor during infancy, which on study proved to be of congenital origin, were analyzed. The breakdown of these cases is as follows: 4 laryngotracheomalacia, 3 vascular anomalies, 4 angiomas, 1 mucous membrane, 1 laryngeal cyst. The remaining cases (18) belong to the so-called "benign" stridor group in that no specific etiology could be demonstrated and in that evolution was spontaneously favorable. In every case of stridor, the precise underlying cause should be looked for. In addition to clinical assessment the investigation of an infant with stridor calls for the following methods of examination: chest x-ray; larynx x-ray (anterior and lateral view) during iopneumography should be confined to specific cases.

Gastroesophageal reflux: a primary defect in cystic fibrosis?

Ten infants and newborns with recently and successively diagnosed cystic fibrosis (CF) were investigated for possible gastroesophageal reflux (GER) by means of pH monitoring over a period of about 20 h. All these patients showed abnormal GER. These patients had a scattered clinical profile of either respiratory or gastrointestinal (GI) manifestations, a poor weight gain, or a combination of these under classical CF treatment. Eight patients underwent treatment with cisapride, a new, potent GI prokinetic drug. This treatment was successful, as documented by almost normal pH monitorings, performed during cisapride therapy, in seven infants. The previous clinical disturbances were evaluated on clinical follow-up study. These significantly improved during cisapride, suggesting that GER can trigger many complications in CF. Anti-reflux therapy could be an important part of the treatment of young CF patients.

Evaluation of time interval difference digital subtraction fluoroscopy in patients with cystic fibrosis.

In this study the potential of thoracic subtraction fluoroscopy has been evaluated on the basis of our experience with this functional imaging modality in patients presenting with cystic fibrosis. The method, which consists of subtracting dynamic digital fluoroscopic images of the breathing chest in the time interval difference (TID) mode, applies to the study of the lucency variations during the respiratory cycle and provides dynamic functional information about ventilation and/or perfusion and diaphragmatic kinetics, without any injection and with minimal irradiation. To assess the validity of the TID procedure, our results were compared with standard roentgenography, clinical data, and scintigraphic findings, with emphasis on the latter. The limitations and advantages of TID compared with scintigraphy are discussed. Three groups of discrepancies emerge which do not discredit TID. TID offers rather the advantage of providing anatomic pictures and unique dynamic information, which is emphasized.