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Paediatric pulmonology and allergology
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Arunas Petronis. Genetics, epigenetics and pharmacogenetics of bronchial asthma Bojarskas J., Vaideliene L., Kudzyte J., Forster J., Arshad H., Hide D., Tsitoura S. SPACE (Study on Prevention of Allergy in Children in Europe): the first stage data Birute Rockaite, Saulius Rocka, Rima Sabaliene, Migle Klimantaviciene, Arunas Valiulis. Allergic diseases and feeding of infants in Lithuania Ingrida Kazlauskiene, Regina Emuzyte, Regina Firantiene, Vytas Tamosiunas. Airway allergic inflammation Jurgis Bojarskas, Valdone Miseviciene, Jolanta Kudzyte. The peculiarities of recurrent wheezing in early childhood Algimantas Vingras. Recurrent and chronic bronchitis in childhood Kaltenis P., Bernatoniene J., Murauskaite G., Bernatoniene G., Kristinsson K., Hjaltested E., Erlendsdottir H. Antimicrobial susceptibility of the most common respiratory tract pathogens in children in Vilnius Irena Narkeviciute, Violeta Baliukynaite, Ona Braskuviene, Laima Naskauskiene. Acinetobacter spp. - real or supposed agent of a disease Edvardas Danila. Bronchial tuberculosis Erika von Mutius. Asthma and wheezy bronchitis Bruce K. Rubin. Advances in the treatment of mucus clearance disorders Bush A., Cole P., Hariri M., Mackay I., Phillips G., O'Callaghan C., Wilson R., Warner J.O. Primary ciliary dyskinesia: diagnosis and standards of care Andrew Bush. Viruses and asthma: causal or coincidental? Andrew Bush. Difficult Asthma: Diagnosis And Management Rubin B.K., Okamoto K., Kishioka C., Arima S., Kim J. Macrolide antibiotics as biologic response modifiers National guidelines of allergic rhinitis Lithuanian standard of medicine: pulmonologist |
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Genetics, epigenetics and pharmacogenetics of bronchial asthma
Arunas Petronis
In this article, epidemiological, clinical, and molecular genetic studies of asthma are reviewed. Asthma belongs to the group of complex non-Mendelian diseases with numerous non-Mendelian features including relatively late age at onset, discordance of monozygotic twins, presence of environmental factors, prevalence of sporadic cases over familiar ones, parent of origin effects and differential penetrance of maternal and paternal alleles, genetic heterogeneity, among others. All these factors impede the molecular genetic studies. However, a number of genome scan-based linkage studies and candidate-gene association studies have been performed, and several loci exhibited strong statistical evidence for linkage and association with asthma. In addition to the more traditional genetic linkage and association designs, epigenetic and pharmacogenetic studies may lead to very interesting developments in understanding of the molecular substrate and the basic etiopathogenic mechanisms of asthma. It is expected that combined genetic, epigenetic and pharmacogenetic approach will assist in creating new and efficient medications for this severe disease.
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SPACE (Study on Prevention of Allergy in Children in Europe): the first stage data
Jurgis Bojarskas, Laimute Vaideliene, Jolanta Kudzyte, Johannes Forster, Hassan Arshad, David Hide, Stella Tsitoura
International SPACE study results about prevalence of atopy in families were compared in between five countries: Germany, England, Greece and Lithuania. Questionnaire's data and skin prick test results showed that 42 perc. of the families has atopy. Atopic symptoms most of all are spread in England: 28 perc. of examined families indicated asthma like, allergic rhinitis and eczema symptoms. Lithuanian families having 20-48 months old children had 2-4 times less allergic symptoms in comparison with other countries and eczema is the most common allergy. Lithuanian fathers are 4.5 times more allergic than mothers and more often they have pollen allergy. English parents more often are allergic to hose dust mites. Eczema was indicated more often by children from atopic families. Asthma like symptoms were mentioned by 36 perc. of Lithuanian children, though asthma was diagnosed only for 6 perc. from them. Asthma like symptoms were mentioned by very similar percentage of children in other countries, but asthma was diagnosed even for 14 perc. of them. Allergic rhinitis was not so common among toddlers, approximately 6 perc. in all the countries.
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Allergic diseases and feeding of infants in Lithuania
Birute Rockaite, Saulius Rocka, Rima Sabaliene, Migle Klimantaviciene, Arunas Valiulis
Epidemiological study was carried out in Vilnius and Utena in 1999. There were used questionnaires, in which parents of 1804 children (mean age - 7.6 years) were interviewed. 15.2 perc. of studied children were diagnosed the allergic disease. A diagnosis of bronchial asthma was present in 2.33 perc., allergic rhinitis - in 1.88 perc., atopic dermatitis - in 2.44 perc. of cases. A diagnosis of food allergy was present in 14.75 perc. of cases. There were great differences of food allowance between the groups of children breast-fed and children without breast-feeding, but the prevalence of allergic diseases was the same in both groups. There were found, that the time of developing of the allergic disease was lattered dependant on breast-feeding. Food allowance of children with and without symptoms of allergic diseases had no statistically significant differences during first 12 months of age. Children from the allergic families were allergic more than children from non allergic families with no differences in their food allowance. It was found later development of allergic diseases in breast-fed group of children.
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Airway allergic inflammation
Ingrida Kazlauskiene, Regina Emuzyte, Regina Firantiene, Vytas Tamosiunas
The representation of allergy as an iceberg explains the consequence of allergy symptoms caused by underlying genetics, sensitization, inflammation and hyperreactivity. Airway inflammation is now recognized play a crucial role in allergic airway diseases. The cardinal features of allergic inflammation, include IgE synthesis, IgE-dependent mast cell activation and infiltration of the airway mucosa with T lymphocytes, eosinophils and mast cells. Effector receptors (FceRI) and by Th2 cell functions, i.e. mast cells, basophiles, eosinophils, are involved in allergic inflammation development in airways. The activated cells release various mediators (e.g. histamine, leukotrienes, prostaglandins, cytokines, etc.) that induce allergic inflammation which results mainly from the combination of six phenomena: cell proliferation, differentiation, priming, chemotaxis, activation/degranulation, and apoptosis inhibition (increased cell survival). The airway inflammation is unique because the airway wall is infiltrated by Th2 lymphocytes, eosinophils and mast cells. These cells contribute to the physiologic changes by their ability to secrete cytokines and/or mediators that damage the airway tissue. Biological markers (cytokines; leukotrienes; proteins contained in the granulae of inflammatory cells; adhesion molecules) reflect the degree of inflammation and/or activation of key inflammatory cells. It has recently been demonstrated that in allergy of airways minimal persistent inflammation (MPI) exist in asymptomatic patients. MPI could be an important factor in the progression from one allergic disease to another. Discovery of MPI, characterized by expression of ICAM-1, now suggests that rhinovirus infection may be a secondary phenomenon in the pathogenesis of asthma.
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The peculiarities of recurrent wheezing in early childhood
Jurgis Bojarskas, Valdone Miseviciene, Jolanta Kudzyte
Wheeze is very common during infancy with approximately 1/3 of infants wheezing at some stage during the first three years of their life. At least 60 perc. of these will be transient wheezers. Others will have early onset of asthma and will continue to wheeze into later childhood. The main risk factors, that cause recurrent wheezing in childhood and factors that could influence the pathogenesis of asthma are discussed in the article. The results of our clinical study of early wheezers (0-3 years of age), who were treated in our hospital, confirm the data that positive family history for atopic diseases in general and infantile atopic dermatitis is strongly associated with recurrent wheezing in early childhood. Respiratory virus infections were the most frequent provoking factor of wheezing in infancy.
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Recurrent and chronic bronchitis in childhood
Algimantas Vingras
The 1997-1998 year data about children morbidity with recurrent bronchitis and chronic pulmonary diseases found at Lithuanian Health Information centre are not accurate. This is because data about morbidity with bronchitis not defined as acute of chronic (J40), simple and mucous-purulent bronchitis (J41), not defined chronic bronchitis (J42), emphysema (J43), bronchektasia (J47) are not differentiated. Children morbidity with all the mentioned diseases altogether increased by 2.45 times during one-year-period. In 1998 there were 4940 children ill with chronic obstructive pulmonary disease. Such a high childhood morbidity with chronic obstructive pulmonary disease is not found in any European countries whish follow the 10th International classification of illnesses. Recurrent bronchitis is proposed to classified as J40, chronic bronchitis (when diagnosed as primary disease) as J41 or J42 (depending on it's character), obstructive bronchitis (up to 3 recurrent episodes) as J20.9. The article describes the definitions and diagnostic criteria for recurrent bronchitis, chronic bronchitis (simple and obstructive), chronic obstructive pulmonary disease, emphysema, the differences between asthma and chronic obstructive pulmonary disease. The causes for chronic cough, risk factors for primary and secondary chronic bronchitis are widely discussed. Primary chronic bronchitis is rare in childhood, most often it is a secondary disease developed as a complication of other lower respiratory tract disease. One of the main guidelines for treatment recurrent and chronic bronchitis is adequate antibacterial therapy. It's effectiveness is increased by restored mucociliar clearance. Anticholinergic drugs should be used in abundant mucous production. Immunomodulating agents decrease the number of episodes in recurrent bronchitis.
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Antimicrobial susceptibility of the most common respiratory tract pathogens in children in Vilnius
Petras Kaltenis, Jolanta Bernatoniene, Grazina Murauskaite, Gina Bernatoniene, Karl Kristinsson, Einar Hjaltested, Helga Erlendsdottir
The aim of this study was to assess the prevalence rates and the antimicrobial resistance of the most common respiratory tract pathogens. Nasopharyngeal swabs were taken from children (1-7 years old) attending day care centers in Vilnius during the period of February - March, 1999. Of the 508 children, 71% carried respiratory tract pathogens: Streptococcus pneumoniae 51%, Haemophilus influenzae 68% and Moraxella catarrhalis 46%. The prevalence of susceptible S.pneumoniae strains to penicillin was 95%. No strains were fully penicillin resistant. ß-lactamase production was 3.5% in H.influenzae and 97.4% in M.catarrhalis. The most frequently used antibiotic was erythromycin (37%). The results of the study should help the physicians to select the most proper antibiotic, especially in the cases of starting empiric treatment in out-patient departments.
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Acinetobacter spp. - real or supposed agent of a disease
Irena Narkeviciute, Violeta Baliukynaite, Ona Braskuviene, Laima Naskauskiene
The aim of this study was establish the prevalence of Acinetobacter spp. in hospitalized children and in the environment of the hospital and to evaluate the susceptibility of Acinetobacter spp. to antibiotics. In 1990-1994 in Vilnius university children's hospital 6822 samples of clinical material and 1203 samples from surrounding objects of hospital were taken. The sensitivity of 95 Acinetobacter spp. isolates to antibiotics was performed using disk diffusion method. Acinetobacter spp. have been isolated in hospitalized patients in 0.45 perc. cases and from hospital environment objects - 2.16 perc.. In most cases positive cultures were in children with respiratory tract diseases Acinetobacter spp. were isolated in 25.8 cases from blood and cerebrospinal liquor. In 1997-1998 Acinetobacter spp. isolates were sensitive to amicacin, polimixin (100 perc.), tobramicin, ceftazidim (93.6, 73.9 perc.), ampicillin, amoxycillin/clavulanic acid, cefaclor, cefamandol, cefotaxim, gentamicin, chloramphenicol (54.2-22.0 perc.). Acinetobacter spp. is a potential pathogen of nosocomial infection, especially in patients in intensive care units.
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Bronchial tuberculosis
Edvardas Danila
30 patients with bronchial tuberculosis were examined in Clinic of Pulmonology and Allergology of Vilnius University Hospital Santariskiu klinikos at 1995-1999 years. Most common clinical signs were: cough in 100 perc. cases, hemoptysis in 23 perc. cases, fever in 63 perc. cases. Chest X-ray revealed segmental/lobar shadowing in 57 perc. cases, rounded shadow in the lung in 10 perc. cases, increased of segmental/lobar lung pattern in 13 perc. cases. There were normal chest X-ray in 20 perc. cases. Bronchoscopy revealed mucosal inflammation and mucosal inflammation with granulation tissue in most cases. Lymph node invasion was detected in 20 perc. cases.
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Asthma and wheezy bronchitis
Erica von Mutius
There is conclusive evidence that the prevalence of wheezing illnesses is on the increase in western, affluent countries. Most of these studies failed, however, to differentiate between different wheezing phenotypes. Longitudinal studies have demonstrated that wheezing is a common symptom occurring in about half of all children up to school age. The natural course of wheezing illnesses clearly points towards different outcomes and risk factors. Transient early wheezing has been related to small airway size, whereas childhood asthma has more frequently been associated with atopy and familial predisposition. Increased exposure to viral infection has been disputed as both risk and protective factor for the development of childhood asthma and atopy.
Annales Nestle 1999; N2, with permission
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Advances in the treatment of mucus clearance disorders
Bruce K. Rubin
Respiratory mucus is a mixture of submucous gland, goblet cell, and epithelial cell secretions. The secretion and transport of mucus requires that mucus exhibit non-Newtonian behavior. Accumulation of mucus can be due to impaired ciliary activity, mucus hypersecretion, and abnormal biophysical properties of mucus. Chronic airway inflammation is associated with mucous gland and goblet cell hypertrophy, increased mucus production, decreased mucus clearance, and changes in sputum properties. Mucokinetic agents improve the cough clearance of secretions by increasing air flow or by decreasing the sputum-epithelium interaction without altering sputum viscoelasticity. Decreased sputum adhesivity is strongly associated with increased cough transportability. Mucoregulatory agents inhibit mucus production or mucus secretion. Anticholinergics can reduce the volume of stimulated secretions without increasing mucus viscosity. Mucus transport by expiratory airflow (including cough) is the primary mucus transport mechanism used by patients with inflammatory pulmonary diseases who have damaged mucociliary development of effective mucoactive therapy and allow us to better determine which patients are most likely to benefit from a specific therapy.
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Primary ciliary dyskinesia: diagnosis and standards of care
Andrew Bush, Peter Cole, Mohamed Hariri, Ian Mackay, Gill Phillips, Christopher O'Callaghan, Robert Wilson, John Oliver Warner
Primary ciliary dyskinesia (PCD) is characterized by disease of the upper and lower respiratory tract, in association with visceral mirror image arrangement in 50 perc. of cases, due to abnormal structure and/or function of cilia. The purpose of this paper is to review the clinical feature, diagnosis and management of PCD. Presentations include neonatal respiratory distress, recurrent lower respiratory tract infection, chronic rhinosinusitis and male infertility. PCD enters the differential diagnosis of bronchiectasis, atypical asthma, and unusually severe upper airway disease. Diagnosis is by a cascade of investigations, starting with the saccharin test in patients older than 10 years; ciliary beat frequency and pattern on light microscopy; and electron microscopy to assess ciliary morphology and orientation. It is important not to confuse primary and secondary ciliary abnormalities. Nasal nitric oxide is low in PCD, and this measurement shows promise as a screening test for PCD. Diagnosis is important, in order to prevent the development of bronchiectases and to avoid any unnecessary otorhinolaryngological procedures. Regular follow-up is essential, and management should be multidisciplinary, with input from centres with a special interest in PCD, having access to paediatric and adult chest physicians, otorhinolaryngologists and audiological physicians, physiotherapists, counseling services and fertility clinics. The prognosis is good, but morbidity can be considerable if PCD is incorrectly managed.
Eur. Respir. J 199;12:982-988, with permission
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Viruses and asthma: causal or coincidental?
Andrew Bush
The relationship between viral infection and respiratory disease is complex. This communication will discuss the following issues: does viral infection cause asthma, or do children who wheeze with colds have pre-existing abnormal lung function; what is the relation between acute viral infection and exacerbation in known asthmatics; what is the relationship between respiratory syncytial virus (RSV) infection, atopy, and long term symptoms; what chronic lung diseases can be caused by acute viral infection? Much viral induced wheeze has its bases in a developmental reduction in baseline airway calibre, rather than eosinophilic airway inflammation. It has been known for many years that viral infection is the commonest trigger for an asthma exacerbation. The balance of the evidence is that RSV does not cause asthma; pre-existing atopy and small airways maldevelopment may predispose to increased severity of the acute episode. Most infants will have a prolonged post-bronchiolitis syndrome of cough and wheeze, which is refractory to treatment with inhaled steroids but gradually improves over time. At the moment the interactions between viruses and the allergic response are difficult to interpret, and a fruitful area for further research. In practice however, at the moment there is no evidence to justify the use of inhaled or oral corticosteroids at any stage of RSV disease, which implies that eosinophilic airway disease is not likely to be clinically important.
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Difficult Asthma: Diagnosis and Management
Andrew Bush
Most children with asthma respond to simple treatment. For those who do not, a systematic approach should be adopted. The purpose of this communication is to suggest ways by which scientific advances in the understanding of asthma may be utilized to try to rationalize the management of this difficult group. Not all difficult asthma is the same in terms of pathopysiological phenotype. The first point to determine is what the family actually mean by the word "wheeze". We need to know more about the different types of difficult asthma to design specific treatment plans. Every effort must be made to identify and correct environmental factors, and offer psychological support where indicated. The best treatment is of course allergen avoidance, but this may not always be possible. There is no justification for the use of immunotherapy in asthma at the present time.
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Macrolide antibiotics as biologic response modifiers
Bruce K. Rubin, Kosuke Okamoto, Chikako Kishioka, Shinobu Arima, Jungsoo Kim
Macrolide antibiotics have a diversity of non-antibiotic properties, the most familiar being motilin receptor stimulation which is primarily responsible for gastrointestinal side effects. The immunomodulatory effects of macrolides have been suspected since the 1960s when it was first reported that troleandomycin enabled some steroid-dependent asthmatic to reduce their dose of prednisolone. The impressive clinical efficacy of macrolides in treating diffuse panbronchiolitis has driven much of the recent interest in the immunomodulatory effects of these antibiotics. Macrolide therapy was beneficial even in patients infected with macrolide resistant P.aeruginosa. A recent letter reported encouraging results of macrolide therapy in a small group of patients with CF. Based on in vitro data there are five major hypotheses that might explain the beneficial effect of long term and low dose macrolide antibiotic therapy in chronic lung disease. Additional research is needed primarily to address the following questions: what is the mechanism of action for these immunomodulatory effects? What is the optimal dosage and duration of use for the treatment of chronic inflammatory diseases? Are there other chronic inflammatory disease that would benefit from macrolide therapy as biologic response modifiers? It is possible that other chronic inflammatory conditions such as arthritis, collagen vascular diseases, and chronic atopic dermatitis or eczema might also benefit but there are no published data related to these other potential uses.
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March, 2000, Vol. III, No.1 (p. 1-160)
