[Cytokine profile in young children with acute stenotic laryngotracheitis].

INTRODUCTION: One of the most severe complications of acute respiratory infections in young children is acute stenotic laryngotracheitis (croup). The relationship between cytokine blood levels and symptoms of croup, croup severity, disease sequel, despite numerous studies is still unclear. AIM: Cytokine profile in young children with acute stenotic laryngotracheitis investigation. MATERIAL AND METHODS: 112 children aged 12 min. - 36 mon. with acute stenotic laryngotracheitis which were treated at the Lviv Regional Infectious Diseases Hospital were kept under observation. Croup symptoms, levels of interleukins (IL1, IL4, IL6, IL10, IL17) in serum, DNA and RNA viruses in respiratory nasal mucus were studied; Chan croup severity was used. RESULTS: In the pathogenesis of croup has an important role the imbalance between inflammatory (IL1, IL6) and anti-inflammatory (IL4, IL10, IL17) cytokines, which does not reduce the intensity of inflammatory reactions and its lead to local swelling, muscle spasm, excessive production of mucus in the place of viral replication. The levels of inflammatory and anti-inflammatory cytokines in the blood serum of children with croup were significantly higher than in patients with acute laryngitis. In patients with recurrent croup, unlike patients with the first case of croup does we don't see a significant correlation between the concentrations of inflammatory and anti-inflammatory cytokine levels Conclusions: The significantly higher levels of cytokines in children with croup compared with the group of patients with acute laryngitis were found, imbalance between anti-inflammatory (IL1, IL6) cytokine levels and inflammatory (IL4, IL10, IL17) cytokine levels in children who developed recurrent croup.

Oesophageal candidiasis and croup in a child with defective neutrophil motility.

Severe oesophageal candidiasis and croup due to involvement of the larynx developed insidiously in a girl aged 20 months. There had been delayed separation of the umbilical cord and repeated infections associated with a defect of neutrophil motility. The significance of the early clinical features was not fully appreciated and the diagnosis considered only when stricture of the oesophagus became evident. She was treated with oral ketoconazole 100 mg daily. After one month's treatment there was striking radiological improvement apart from the persistence of the oesophageal stricture. The croup resolved completely but there was only partial relief of dysphagia because of the residual stricture. We would emphasis that candidiasis should be anticipated and treated vigorously in children with such a defect of neutrophil motility.

The relation between recurrent acute subglottic laryngitis and asthma in children.

OBJECTIVE: Acute subglottic laryngitis is caused by some viruses and may recur several times in children. Risk factors underlying the recurrences of this disease are obscure. The present study was undertaken to investigate the relation between acute subglottic laryngitis, asthma and allergy. METHODS: Twenty five children with recurrent acute subglottic laryngitis were evaluated for risk factors for recurrent respiratory tract infections and allergy. Eight of the children had high IgE levels and six of them were found to be allergic by skin prick tests. RESULTS: During a 1 year follow-up period four children showed asthma symptoms and in three of these patients recurrences of croup attacks disappeared after asthma treatment with nebulized budesonide. CONCLUSION: We concluded that recurrent acute subglottic laryngitis may be an early sign of subsequent asthma development.

[Recurring croup. New clinical, pathophysiological and etiological aspects]. / Der rezidivierende Krupp. Neue klinische, pathophysiologische und ätiologische Aspekte.

Three consecutive studies were concerned with clinical, pathophysiologic, and immunologic aspects of recurrent croup. The first investigation demonstrated that recurrent croup is a distinct disease entity which shares many clinical features with asthma and should be distinguished from viral laryngotracheobronchitis. In the second study a high incidence of airway hyperreactivity was found in children with recurrent croup. This specific type of hyperreactivity suggested an involvement of both the lower and the upper respiratory tract. The third study demonstrated a tendency towards low serum IgA levels in children with recurrent croup; hence immunoregulatory defects may be conductive to the development of this disorder.

[Indices of T-lymphocytes and their subpopulations in children with influenza]. / Pokazateli T-limfotsitov i ikh subpopuliatsii u detei pri grippe.

The results of the study of T lymphocytes and their subpopulations in 150 children ranging in age from 2 months to 5 years suffering from influenza complicated with croup, pneumonia, and obstructive syndrome are presented. In 47 children, mixed infection: influenza with concomitant adenovirus infection or respiratory-syncytial infection was observed. The control group consisted of 22 normal children. In the acute period of influenza the number of T lymphocytes and their subpopulations was found to decrease. The greatest decrease in the levels of T lymphocytes and especially of E-theophylline-sensitive ones was observed in cases complicated with pneumonia and obstructive syndrome. In mixed infections, inhibition of E-RFC and their subpopulations was more marked in influenza and adenovirus disease. The data obtained by catamnestic observations of children with lowered levels of T lymphocytes suggest that such children should be referred to a risk group and apparently require immunocorrective therapy.

Pathogenesis of acute respiratory illness caused by human parainfluenza viruses.

Human parainfluenza viruses (HPIVs) are a common cause of acute respiratory illness throughout life. Infants, children, and the immunocompromised are the most likely to develop severe disease. HPIV1 and HPIV2 are best known to cause croup while HPIV3 is a common cause of bronchiolitis and pneumonia. HPIVs replicate productively in respiratory epithelial cells and do not spread systemically unless the host is severely immunocompromised. Molecular studies have delineated how HPIVs evade and block cellular innate immune responses to permit efficient replication, local spread, and host-to-host transmission. Studies using ex vivo human airway epithelium have focused on virus tropism, cellular pathology and the epithelial inflammatory response, elucidating how events early in infection shape the adaptive immune response and disease outcome.

The relationship between allergy and croup.

The relationship between allergy and croup is examined addressing possible associations between croup and IgE antibody production, and between croup and atopic allergic disorders irrespective of the presence or absence of IgE antibody. A case can be made for an increased association between allergy and recurrent croup. Children with croup are more likely to produce IgE antibodies than normal children without croup and there is an association between the production of IgE antibody to certain respiratory viral infections and the development of croup. There also is an increased association between croup, asthma and nonspecific bronchial hyperresponsiveness associated with asthma.

The management of croup.

Croup is a common paediatric respiratory illness involving inflammation and narrowing of the subglottic region of the larynx, frequently precipitated by viral infections. Treatment is aimed at decreasing symptoms and reducing inflammation. Glucocorticoids are effective by oral, parenteral or nebulized routes, and continue to provide the mainstay of therapy. The common oral dexamethasone dose (0.6 mg/kg) may exceed the dose required for good clinical efficacy. Nebulized epinephrine provides effective additional therapy for more severe cases. L-epinephrine appears to be comparable to racemic epinephrine, although further study is warranted. Limited data suggest that heliox is also effective in the short-term management of refractory croup. The use of humidified oxygen remains controversial, as good data are lacking.

Role of parainfluenza virus-specific IgE in pathogenesis of croup and wheezing subsequent to infection.

In order to determine the role of parainfluenza virus-specific IgE antibody production and release of histamine in the pathogenesis of lower respiratory disease caused by parainfluenza virus infection, we studied 84 infants and children at the time of parainfluenza virus infection. Parainfluenza virus-IgE antibody was detected in samples of nasopharyngeal secretions by means of an enzyme-linked immunosorbent assay, and histamine content of nasopharyngeal secretions was determined by a fluorometric technique. Virus-specific IgE responses appeared earlier and were of greater magnitude in patients with croup, wheezing, and croup with wheezing caused by parainfluenza virus infection than in patients with parainfluenza virus-induced upper respiratory illness. Histamine was detectable in nasopharyngeal secretions of patients with parainfluenza virus-related croup significantly more often than in patients with upper respiratory illness caused by parainfluenza virus. These observations suggest a role for immunologic mechanisms in the pathogenesis of severe forms of respiratory illness caused by parainfluenza virus infection.

Airway reactivity in recurrent croup.

Three subsequent studies were concerned with clinical, pathophysiologic and immunologic aspects of recurrent croup. The first investigation demonstrated that recurrent croup is a distinct disease entity which shares many clinical features with asthma and should be distinguished from viral laryngotracheobronchitis. A high incidence of airway hyperreactivity was found in children with recurrent croup in the second study. This specific type of hyperreactivity suggested an involvement of both the lower and the upper respiratory tract. The third study demonstrated a tendency towards low serum IgA levels in children with recurrent croup; hence immunoregulatory defects may be conducive to the development of this disorder.

Influenza A and B virus infection in infants and young children during the years 1957-1976.

Influenza A virus activity was demonstrated in infants and young children from metropolitan Washington, DC during each of 19 successive August-July respiratory disease years, and during 17 of these years at least 2% of hospitalized respiratory disease patients yielded an influenza A or B virus and/or showed an influenza A or B serum complement-fixing (CF) antibody response. Between October 1957 and July 1976, 14.3% of 860 croup patients and 5.3% of a total of 5655 hospitalized respiratory patients, including croup patients, showed evidence of influenza A or B infection. The mean period of hospitalization with either virus was about 8 days, though serious infection with influenza A virus was 4.5 times more common than with influenza B virus. Both influenza viruses were detected more frequently in respiratory disease outpatients than in respiratory disease inpatients. Patients with serious influenza A virus infections were especially likely to have croup (particularly during the H3N2 era), to be seen during December through February, and to be black male infants. During the peak month of a composite of 13 consecutive influenza A virus outbreaks, influenza A virus infection was demonstrated in 67.6% of croup patients and in 35.6% of all hospitalized respiratory patients including croup patients. During the peak month of a composite of 6 consecutive influenza B virus outbreaks, influenza B virus infection was demonstrated in 36.0% of croup patients and in 10.8% of all hospitalized respiratory disease patients including croup patients.

Defective regulation of immune responses in croup due to parainfluenza virus.

In order to determine if defects in regulation of immune responses play a role in the pathogenesis of croup, we studied 37 infants and children with either croup or upper respiratory illness alone due to parainfluenza virus (PV). PV-specific IgE responses were determined by an enzyme-linked immunosorbent assay, cell-mediated immune responses to PV antigen were studied by in vitro lymphocyte transformation assays, and suppressor cell function was determined by addition of histamine to lymphocyte transformation assays. In comparison to patients with upper respiratory illness alone, patients with croup had increased production of PV-specific IgE antibody, increased lymphoproliferative responses to PV antigen, and diminished histamine-induced suppression of lymphocyte transformation responses to PV. These results suggest that a defect in suppressor function exists among croup patients. Similar defects have been demonstrated in bronchiolitis and atopic diseases, providing an immunologic link between the three illnesses.