MR imaging findings of bone marrow changes in patients with cystic fibrosis.

The purpose of this work was to evaluate bone marrow abnormalities in the lower limbs of patients with cystic fibrosis by means of MR imaging. Eight patients with cystic fibrosis ranging in age from 16 to 35 years (average age 25.1 years) were evaluated with MR imaging of the lower extremities. T1 weighted spin echo sequences were obtained in all patients. Pelvis, femora and tibia were imaged in the coronal plane whereas the feet were imaged in the sagittal plane. The studies were independently evaluated by two musculoskeletal radiologists. The images were not mixed with disease-free images, but the readers were completely unaware of clinical data. Distribution of haematopoietic and fatty marrow was graded on a 5-point scale. In five patients, both observers considered marrow distribution as probably or definitely abnormal relative to their age. Although our findings are very preliminary, our investigation suggests that cystic fibrosis may be added to the list of disorders in which bone marrow abnormalities may be observed.

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.

Dose-finding and 24-h monitoring for efficacy and safety of aerosolized Nacystelyn in cystic fibrosis.

The aim of the present studies was to investigate the tolerability and activity of a novel mucolytic drug, Nacystelyn (NAL), for the treatment of cystic fibrosis (CF) lung disease. In study 1, involving 10 CF patients, the main objective was to determine the tolerability and potential efficacy of a range of single doses of NAL in comparison to a placebo, in order to establish an optimal dose for further testing. On five consecutive scheduled treatment days, patients inhaled either from two (4 mg) to eight puffs (16 mg) of a single dose of NAL from the range, administered in an open-label fashion, or 12 puffs of active NAL (24 mg) versus 12 puffs of placebo, administered in a randomized double-blind fashion. Pulmonary function data were unaffected and clinically-adverse effects were limited to wheezing in some patients that inhaled 12 puffs of either placebo or active drug. Subsequent rheological analysis of their sputum showed a dose-dependent decrease in sputum viscoelasticity, accompanied by a decrease in sputum solids content and an increase in chloride and sodium concentrations. In study 2, involving 12 CF patients, the clinical safety and mucolytic activity of a single dose of NAL was monitored over 24 h. On different scheduled treatment days, 7 days apart, patients inhaled a single dose of 12 puffs of active NAL (24 mg) or 12 puffs of placebo drug in a randomized, double-blind sequence, with sputum samples taken at intervals before and after inhalation. Mucus rigidity decreased following NAL inhalation, with the maximum effect observed at 4 h; the 1-, 2- and 4-h NAL rheology results were significantly different from placebo. No adverse effects were observed. The drug was well tolerated in both studies. Sputum results were predictive of improved clearability by ciliary and cough transport mechanisms.

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.

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.

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.

Burkholderia (Pseudomonas) cepacia and cystic fibrosis: the epidemiology in Belgium.

Burkholderia cepacia has become an increasingly recognized pathogen among cystic fibrosis (CF) patients and its potential role in declining pulmonary function or unexpected fatal outcome has caused widespread concern. Direct person-to-person transmission has been documented and a segregation policy of CF patients colonized with B.cepacia from non-colonized CF patients is widely adopted. Since this policy has a dramatic impact on social behaviour of CF patients it is imperative that clinical laboratories accurately isolate and identify B.cepacia in the respiratory secretions. In order to comprehend the epidemiology of B.cepacia in the Belgian CF population a multicentre study was conducted during a period of 1 year (March'93-February'94). B.cepacia was isolated in only 12 of 465 CF patients (2.6%). Routine biochemical tests identified these strains as authentic B.cepacia. However, the combined data from protein and DNA-DNA hybridization analyses revealed that the Belgian CF "B.cepacia" isolates showed patterns different from reference B.cepacia isolates and belong to 3 different, newly identified Burkholderia genomovars, but not to B.cepacia. Comparative analysis of the selective media used for recovery of these "B.cepacia" strains from respiratory secretions indicated that the commercial medium (Mast) containing polymyxin B and ticarcillin as the selective agents was the best and most user-friendly. Molecular typing of these Burkholderia isolates by arbitrarily-primed PCR (AP-PCR) and pulsed-field gel electrophoresis (PFGE) showed that spread of a single strain within a same centre occurred but the mode of transmission remains unknown; inter-centre spread of strains was not observed. Interestingly, neither colonization with a distinct or an epidemic strain (belonging to either of the three newly identified Burkholderia genomovars) nor colonization for a prolonged period of time, led to a rapid deterioration of lung function in these CF patients. It appears essential to determine the prevalence of these "new" Burkholderia genomovars in larger populations of CF patients and to evaluate their virulence and other features as this may have important clinical and practical implications.

The long-term effect of a partial whey hydrolysate formula on the prophylaxis of atopic disease.

At the age of 5 years, the prevalence of atopic manifestations was analysed in 58 formula-fed "at risk" infants because of a history of atopic disease in at least two first degree relatives. Infants were randomly assigned to receive either a partial whey-hydrolysate formula (n: 28) or a regular cow's milk formula (n: 30) during the first 6 months of life; thereafter, feeding was unrestricted. Only non-breastfed infants were included. The groups did not differ in risk factors or in known confounding factors possibly influencing the incidence of manifestations suggestive of atopic disease. At 6 months, the prevalence of cow's milk protein (CMP) sensitivity was significantly decreased in the hydrolysate group (7% versus 43%; P: 0.002). At the age of 12 (21% versus 53%; P: 0.029), 36 (25% versus 57%; P: 0.018) and 60 months (29% versus 60%; P: 0.016) there was still a significant difference in the number of atopic manifestations, if calculated cumulatively. There was no difference between the groups if only the new cases after the age of 6 months were considered. Eczema was less frequent in the whey-hydrolysate group, but only during the 1st year of life, suggesting a decreased prevalence of CMP sensitivity. During the first 6 months, diarrhoea of non-infectious origin occurred in 8/30 infants (27%) of the adapted formula group, and in no infant in the hydrolysate group. "Colic as single manifestation" was considered of "allergic" origin in 1/28 infants in the hydrolysate group, and in 4/30 infants in the adapted formula group.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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.

Respiratory syncytial virus lung infection in infants: immunoregulatory role of infected alveolar macrophages.

Thirteen previously healthy children with acute onset of severe lower respiratory tract signs and symptoms underwent bronchoscopy and bronchoalveolar lavage (BAL) for diagnostic purposes. BAL samples were assessed for viral, bacterial, mycobacterial, and fungal cultures. Cytospin preparations of BAL cells were assessed for expression of respiratory syncytial virus (RSV), HLA-DR, interleukin-1 beta, and tumor necrosis factor proteins. Purified alveolar macrophages from 2 RSV-infected children were assessed for viral replication. Three children had bacterial pneumonia and 6 were infected with RSV. BAL cells from RSV-infected children demonstrated viral protein expression. Alveolar macrophages were the predominant cell type recovered by BAL and demonstrated coexpression of RSV, HLA-DR, interleukin-1 beta, and tumor necrosis factor proteins. Purified alveolar macrophages from 2 RSV-infected children replicated RSV by infectious center assays. Thus, alveolar macrophages are infected by RSV in vivo and coexpress potent immunomodulatory molecules that potentially regulate the local immune response or lung injury due to this virus.

Elemental composition of human airway surface fluid in healthy and diseased airways.

The fluid that covers the surface of conducting airways (airway surface fluid, ASF) is a critical component of one of the first defense mechanisms of the lung against microbial and other environmental insults. Despite its physiologic importance, ASF is one of the only fluids in the human body whose composition remains poorly defined and understood. Attempts to analyze ASF have been hampered greatly by the fact that it exists only as a very thin layer covering the mucosal surface of airway epithelia. To overcome some of these limitations, we have applied ultramicroanalytic techniques to microsamples collected in human airways in vivo. In contrast to previous thinking from studies on sputum samples, ASF collected from healthy airways contains much less Na and Cl (approximately 45% less) and much more K (around 600% more) than extracellular fluid or plasma (ECF), which shows that steep ion gradients exist across normal airway epithelia. These differences also show that ASF composition must be regulated and maintained by active electrolyte transport processes of airway epithelia and that it is not merely the evaporated residue of isotonic secretions or extracellular fluid exudate. However, in patients with sustained airway irritation, infection, or cystic fibrosis, we find that ASF composition appears to become more isotonic with respect to plasma and much more hypotonic in patients with asthma.