Primary ciliary dyskinesia: a consensus statement on diagnostic and treatment approaches in children.

Primary ciliary dyskinesia (PCD) is associated with abnormal ciliary structure and function, which results in retention of mucus and bacteria in the respiratory tract, leading to chronic oto-sino-pulmonary disease, situs abnormalities and abnormal sperm motility. The diagnosis of PCD requires the presence of the characteristic clinical phenotype and either specific ultrastructural ciliary defects identified by transmission electron microscopy or evidence of abnormal ciliary function. Although the management of children affected with PCD remains uncertain and evidence is limited, it remains important to follow-up these patients with an adequate and shared care system in order to prevent future lung damage. This European Respiratory Society consensus statement on the management of children with PCD formulates recommendations regarding diagnostic and therapeutic approaches in order to permit a more accurate approach in these patients. Large well-designed randomised controlled trials, with clear description of patients, are required in order to improve these recommendations on diagnostic and treatment approaches in this disease.

The effect of allergic rhinitis on adenosine concentration in exhaled breath condensate.

BACKGROUND: Patients with allergic rhinitis (AR) frequently develop asthma. This initiating inflammation in the lower airways may result in increased levels of inflammatory mediators such as adenosine in the exhaled breath. OBJECTIVE: We compared adenosine levels in exhaled breath condensate (EBC) and both exhaled and nasal nitric oxide (NO) levels of AR patients and healthy control subjects. We also tested whether inhalation through inflamed nasal cavity during EBC sampling influences adenosine concentrations in exhaled air. METHODS: Exhaled and nasal NO levels were measured and EBC samples (at oral inhalation) were collected from 27 patients and 15 healthy controls. EBC collection was repeated after 15 min with subjects inhaling through their nose. Adenosine was measured by HPLC and NO was determined by chemiluminescence. RESULTS: The concentration of EBC adenosine was higher in patients with AR than in healthy controls (12.4+/-1.3 nM vs. 6.5+/-0.7 nM, P=0.0019) and this was accompanied by an increase in the concentration of exhaled NO (10.2+/-1.3 ppb vs. 5.3+/-0.5 ppb; P=0.0099, respectively). No difference in nasal NO was detected. EBC adenosine concentration showed a significant positive correlation with the level of exhaled NO. In contrast to healthy control subjects, patients with rhinitis had higher levels of exhaled adenosine when inhaling via the nose instead of the mouth (17.7+/-2.8 nM, P=0.007). CONCLUSION: When compared with healthy subjects, patients with AR exhibit an increased concentration of exhaled adenosine and a related increase in exhaled NO concentration. EBC adenosine is further increased when rhinitis patients inhale through their nose than via their mouth. Our data suggest that non-asthmatic patients with rhinitis may have subclinical inflammation in their lower airways.

Factor XIII in bronchoalveolar lavage fluid from children with chronic bronchoalveolar inflammation.

BACKGROUND: Extravascular activation of the coagulation system and consequent fibrin deposition is involved in the pathomechanism of chronic bronchoalveolar inflammatory diseases. The turnover of extravascular fibrin is attenuated by its cross-linking with activated factor XIII (FXIII). OBJECTIVES: Determination of cellular and plasmatic forms of FXIII and their correlation with D-dimer level in the bronchoalveolar lavage fluid (BALF) from healthy children and from children with bronchoalveolar inflammation. PATIENTS AND METHODS: Highly sensitive immunoassays were used for the quantitation of cellular and plasma FXIII and D-dimer in the BALF of children with recurrent wheezy bronchitis and fibrosing alveolitis. BALF was investigated for FXIII-containing cells by flow cytometry. RESULTS AND CONCLUSIONS: In the BALF of controls a low amount of the cellular form of FXIII (FXIII A2) and D-dimer were measured, while plasma FXIII (FXIII A2B2) was absent. Alveolar macrophages represented the single cell population in BALF that contained FXIII. In the BALF of both patients' groups the concentration and the total amount of FXIII A2 was significantly elevated, and plasma FXIII also appeared in the BALF of most patients. The D-dimer concentration was also elevated in the patients' groups and it correlated both with plasma FXIII and neutrophil count. These findings suggest that FXIII A2 is released from activated or injured alveolar macrophages into the bronchoalveolar lining fluid and in bronchoalveolar inflammatory diseases, FXIII A2B2 also leaks out from the capillaries. By cross-linking fibrin and inhibitors of fibrinolysis to fibrin, FXIII might be a key regulator of fibrin turnover in the extravascular compartment.

[Significance of anamnestic factors in the background of pathologic airway alterations]. / Az anamnesztikus tényezók jelentósége a légutak anatómiai elváltozásainak hátterében.

The results of 867 diagnostic bronchoscopies, between August 1992 and August 1993, were studied by the retrospective analysis of the patients' files. The average age of the children was 46 months (6 days-25 years). The proportion of girls and boys were 38.6% and 61.4%. Data of the history were: therapy resistant recurrent wheezy bronchitis in 31.9%, recurrent pneumonia in 31.1%, stridor in 22.1%, recurrent croup in 17.4%, bronchial asthma in 10.1%, monosymptomatic cough in 9.5% and recurrent bronchitis in 8.0%. The 768 (89%) pathologic findings were: 1. by bronchoscopy (n = 867): acute inflammation of the mucous membrane 7.3%, chronic bronchitis 75.1%, mucous secretion 44.5%, purulent secretion 20.8%, cricoid stenosis 4.6%, tracheal stenosis 11.2%, left main stem bronchus stenosis 27.8%; 2. by bronchography (n = 202): bronchial deformation 43.1%, bronchiectasis 5.4%, gracile bronchi 2.0%. The following significant relations were proved between the anamnesis and the results of the bronchoscopy and/or bronchography by statistical analysis: recurrent wheezy bronchitis/chronic bronchitis (p < 0.001; chi 2 = 16.35), approximately/purulent secretion (p = 0.039; chi 2 = 4.26), approximately/left main stem bronchus stenosis (p < 0.001; chi 2 = 19.27); stridor/tracheal stenosis (p < 0.001; chi 2 = 58.67), approximately/left main stem bronchus stenosis (p < 0.001; chi 2 = 63.45), approximately/cricoid stenosis (p = 0.0015; chi 2 = 10.8), approximately/other stenosis (p = 0.002; chi 2 = 9.69); recurrent croup/cricoid stenosis (p < 0.001; chi 2 = 18.34); bronchial asthma/bronchial deformation (p = 0.026; chi 2 = 4.95). The results show the importance of the bronchological examination in the diagnosis of chronic chest symptoms in children.

[Ultrastructural study of bronchial mucosa in suspicion of ciliary dyskinesia]. / A hörgónyálkahártya ultrastrukturális vizsgálata ciliaris dyskinesia gyanúja esetén.

In the ciliary dyskinesia (immotile cilia syndrome) shows the partial or total lacking of cilia's elements. The ciliary dyskinesia may be developed congenital or acquired. The authors report on the experience with 72 biopsies from bronchial mucosa of 68 children, submitted with the question of immotile cilia syndrome. On micrographs (M: 64,000x) of the specimens processed by routine electron microscopical method the number of outer and inner dynein arm, A and B peripheral tubules, central tubules and central sheet were determined to normal 9 + 2 structure. 50-100 ciliaris per case were examined. Total or partial lacking of dynein and non-dynein elements were expressed for the total number of ciliaris compartments. Considering any earlier quantitative examination with this expression there was ease to characterised the quantitative behaviour of the components of ciliaris. Seven Kartagener's syndrome cases was the positive control for determined the quantitative differences between the primer and secondary ciliary changes. In the primary ciliary defects where the situs inversus were presented the total lacking of outer or/and inner dynein arms, where the situs inversus were not presented only the total lacking of inner dynein arms could be found. In secondary ciliary defects the partial lacking of the dynein arms and tubular components were presented. The used method is suitable to characterise the primary or secondary ciliary defects of bronchial mucosa.

Use of midazolam ('Dormicum') and flumazenil ('Anexate') in paediatric bronchology.

One hundred and seven bronchological examinations using midazolam narcosis in association with flumazenil were carried out in 100 children (mean age 3.5 years, range 4 months to 14 years) suffering from chronic non-specific lung disease. Rigid bronchoscopy was followed in 49 cases by bronchography. All patients were premedicated with atropine followed by midazolam (0.2 mg/kg intravenously). Ventilation was carried out with nitrous oxide and oxygen in 47 children and with oxygen only in 60 patients. After 3 mins, suxamethonium (2 mg/kg intravenously) was given for muscle relaxation and intubation carried out. Fifty-one of the children ventilated with oxygen only also received fentanyl (0.002 mg/kg intramuscularly), at the same time as atropine, to provide analgesia. After extubation, all patients were given flumazenil (0.1 to 0.2 mg intravenously) to reverse the effects of midazolam. The results showed that midazolam provided effective sedation and comfortable sleep (mean examination time 12 min 50 sec) and it was considered that the method using fentanyl rather than nitrous oxide for analgesia was the most satisfactory one. Patients awakened promptly (1 min) after flumazenil and quick and effective expectoration was noted, particularly important in those who had undergone bronchography. No complications were observed. Since this investigation, a further 500 bronchoscopics have been carried out using this method with the same results. Even though no narcosis equipment is required, it is recommended that, as with other procedures involving narcosis with muscle relaxation, bronchoscopy with these drugs should not be used in out-patients.

[About the incidence of chronic airway diseases in infants and children (author's transl)]. / Zur Frage des Vorkommens chronischer Luftwegserkrankungen im Säuglings- und Kindesalter.

Based on the experiences with 1,500 infants and children, hospitalized during a five-year period, who had undergone clinical, routine laboratory, immunological bacteriological, allergological, X-ray, oto-rhino-laryngological, spirometrical and bronchological examinations performed by unchanging teams using the same methods and instruments, it was found that the cause of respiratory diseases in a comparatively high number of patients were developmental anomalies, that it is important to look for tracheal stenoses, that there is chronic bronchitis in infants and children, that sinusitis maxillaris or shortage of immunoglobulins are relatively rare, and that selective bacteriological cultures are not very often positive. These results emphasize the importance of carefully differentiating between the various forms of respiratory diseases in infants and children.