Correlation of computed tomography findings and lung function in children and adolescents with cystic fibrosis.

BACKGROUND: The timely and appropriate monitoring of pulmonary status is of utmost importance for patients with cystic fibrosis (CF). Computed tomography (CT) has been used in clinical and research settings for tracking lung involvement in CF patients. However, as CT delivers a considerable amount of radiation, its sequential use in CF patients remains a concern. The application of CT, therefore, should take into account its potential risks. This review aims to understand whether and to what extent the CT findings correlate with the findings from other monitoring tools in CF lung disease. DATA SOURCES: PubMed was searched for articles about the correlation of chest CT findings with spirometric indices and with lung clearance index in children and adolescents with CF. The most relevant articles were reviewed and are presented herein. RESULTS: Most studies have shown that forced expiratory volume in the first second (FEV1) and other spirometric indices correlate moderately with CT structural lung damage. However, at the individual level, there were patients with FEV1 within the normal range and abnormal CT and vice versa. Furthermore, longitudinal studies have indicated that the deterioration of structural lung damage does not occur in parallel with the progression of lung function. Lung clearance index is a better predictor of CT findings. CONCLUSIONS: In general, the existing studies do not support the use of lung function tests as surrogates of chest CT.

Adherence to the Mediterranean diet and inflammatory markers in children with asthma

Introduction: There is accumulated evidence supporting a beneficial role of Mediterranean diet (MD) in the control of asthma symptoms. The aim of this study was to investigate the relationships between adherence to MD and serum levels of certain cytokines namely, interleukin (IL)-4, and IL-17 known to have a pathogenetic role in the airway changes associated with asthma. Methods: We measured serum IL-4, IL-33, and IL-17, in 44 asthmatic and 26 healthy children, 5-15 years old. Their adherence to MD was estimated with the Mediterranean Diet Quality Index for children and adolescents (KIDMED) score. Results: KIDMED score did not differ between the two groups (P = 0.59) and was not correlated with any of the three measured cytokines. However, when the analysis was restricted only to asthmatic children, the KIDMED score was correlated with IL-4, IL-33, and IL-17 (Beta: -0.56, P = 0.007; Beta: 0.57, P = 0.010; Beta: -0.62, P = 0.017, respectively). Conclusion: Our results indicate that MD can modulate the production of some of the main inflammatory mediators of asthma, in asthmatic children

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Applications of lung clearance index in monitoring children with cystic fibrosis.

A sensitive, reproducible and feasible measure of lung function for monitoring the respiratory health is a prerequisite for the optimization of management of the patients with cystic fibrosis (CF). Spirometry has been considered the method of choice, although it is applicable only in children older than 6 years of age, as good cooperation is necessary for its proper performance. However, over the last 15 years, scientific interest in gas dilution techniques and particularly in multiple breath wash out (MBW) method has been revived. The most commonly reported index of MBW is lung clearance index (LCI). The aim of this review is to present the most recent developments in the application of LCI as a monitoring index of respiratory status of CF patients. LCI is a sensitive and reproducible marker of ventilation inhomogeneity. It is more sensitive than spirometry and, unlike spirometry; it can be performed across the whole pediatric age range. Since it is dependent on body size, until at least the age of 6 years, the relative and not the absolute changes are more appropriate for providing clinically meaningful conclusion on ventilation inhomogeneity. Until now, MBW has been mainly used as a research tool. Based on the currently available data LCI cannot safely predict high-resolution computed tomography findings in children with CF, especially in infants. It can be used as an end-point measure for the assessment of beneficial effect of interventions. However, its utility as an outcome measure for the efficacy of therapeutic interventions seems to be dependent on the pathophysiologic mechanisms that underlie each intervention. It seems that more studies, especially longitudinal ones, are required in order to fully clarify the clinical usefulness of LCI, not only in the research setting, but also in every day practice of CF clinic.

Adherence to the Mediterranean diet and inflammatory markers in children with asthma.

INTRODUCTION: There is accumulated evidence supporting a beneficial role of Mediterranean diet (MD) in the control of asthma symptoms. The aim of this study was to investigate the relationships between adherence to MD and serum levels of certain cytokines namely, interleukin (IL)-4, and IL-17 known to have a pathogenetic role in the airway changes associated with asthma. METHODS: We measured serum IL-4, IL-33, and IL-17, in 44 asthmatic and 26 healthy children, 5-15 years old. Their adherence to MD was estimated with the Mediterranean Diet Quality Index for children and adolescents (KIDMED) score. RESULTS: KIDMED score did not differ between the two groups (P=0.59) and was not correlated with any of the three measured cytokines. However, when the analysis was restricted only to asthmatic children, the KIDMED score was correlated with IL-4, IL-33, and IL-17 (Beta: -0.56, P=0.007; Beta: 0.57, P=0.010; Beta: -0.62, P=0.017, respectively). CONCLUSION: Our results indicate that MD can modulate the production of some of the main inflammatory mediators of asthma, in asthmatic children.

Is obesity related to the lung function of non-asthmatic children?

Overweight and obesity are highly prevalent in developed and developing countries among children and adolescents. During the last two decades, it became evident that excess weight is adversely related to respiratory health in childhood and adolescence mainly in terms of asthma occurrence. Additionally, there is a mounting body of evidence that overweight/obesity may also affect lung function in non-asthmatic subjects. The aim of this review was to present and discuss the studies that investigated this issue in non-asthmatic children and adolescents. Only a few studies have evaluated the impact of excess weight on static volumes and their results point towards an inverse relationship between overweight/obesity and functional residual capacity. More studies have been conducted on the impact of excess weight on dynamic lung volumes with inconsistent, however, results. Nevertheless, a relatively consistent finding was that the ratio of forced expiratory volume in 1 s/forced vital capacity was significantly lower among overweight/obese children compared to their counterparts with normal weight. The underlying mechanisms of these observations have not been adequately elucidated but it is believed to result from complex interaction of mechanical, developmental, and metabolic causes. There is a need for more well-designed studies in order to clarify the impact of excess weight on lung function in non-asthmatic subjects, as well as to explore the contribution of factors such as duration and degree of obesity, and fat distribution. Despite the absence of conclusive data, there are still convincing evidence to be communicated to the children and their families as part of the arguments to encourage them to adopt a healthier lifestyle.

Differentiating vocal cord dysfunction from asthma.

Vocal cord dysfunction (VCD)-associated symptoms are not rare in pediatric patients. Dyspnea, wheezing, stridor, chest pain or tightness and throat discomfort are the most commonly encountered symptoms. They may occur either at rest or more commonly during exercise in patients with VCD, as well as in asthmatic subjects. The phase of respiration (inspiration rather than expiration), the location of the wheezing origin, the rapid resolution of symptoms, and the timing occurring in relation to exercise, when VCD is exercise induced, raise the suspicion of VCD in patients who may have been characterized as merely asthmatics and, most importantly, had not responded to the appropriate treatment. The gold standard method for the diagnosis of VCD is fiberoptic laryngoscopy, which may also identify concomitant laryngeal abnormalities other than VCD. However, as VCD is an intermittent phenomenon, the procedure should be performed while the patient is symptomatic. For this reason, challenges that induce VCD symptoms should be performed, such as exercise tests. Recently, for the evaluation of patients with exercise-induced VCD, continuous laryngoscopy during exercise (such as treadmill, bicycle ergometer, swimming) was used. A definite diagnosis of VCD is of importance, especially for those patients who have been erroneously characterized as asthmatics, without adequate response to treatment. In these cases, another therapeutic approach is necessary, which will depend on whether they suffer solely from VCD or from both conditions.

Etiology and clinical features of viral bronchiolitis in infancy.

BACKGROUND: Bronchiolitis is a common lower respiratory tract infection in infancy. The aim of this review is to present the clinical profile of viral bronchiolitis, the different culprit viruses and the disease severity in relation to the viral etiology. DATA SOURCES: Databases including PubMed and Google Scholar were searched for articles about the clinical features of bronchiolitis and its viral etiology. The most relevant articles to the scope of this review were analyzed. RESULTS: Currently there are two main definitions for bronchiolitis which are not identical, the European definition and the American one. The most common viral pathogen that causes bronchiolitis is respiratory syncytial virus which was identified in 1955; now many other viruses have been implicated in the etiology of bronchiolitis such as rhinovirus, adenovirus, metapneumovirus, and bocavirus. Several studies have attempted to investigate the correlation of bronchiolitis severity with the type of detected virus or viruses. However, the results were not consitent. CONCLUSIONS: For the time being, the diagnosis of bronchiolitis remains clinical. The isolation of the responsible respiratory pathogens does not seem to confer to the prognosis of the disease severity.

Clinical spectrum of primary ciliary dyskinesia in childhood.

Although the triad of bronchiectasis, sinusitis and situs inversus was first described by Kartagener in 1933, the clinical spectrum of primary ciliary dyskinesia is still under investigation. Heterotaxy defects as well as upper and lower respiratory tract symptoms are the main manifestations in childhood. It is now recognized that situs inversus is encountered in only half of patients. The first lower respiratory symptoms may be present from infancy as neonatal respiratory distress. The most common lower airway manifestations are chronic wet cough, recurrent pneumonia and therapy resistant wheezing. Patients are at risk of developing bronchiectasis which may even be the presenting finding due to delayed diagnosis. Upper respiratory tract infections such as nasal congestion, nasal drainage and recurrent sinusitis as well as otologic manifestations such as otitis media or otorrhea with conductive hearing loss are also often encountered. It seems that the type of ciliary ultrastructure defects and the involved mutated genes are associated to some extent to the clinical profile. The disease, even in nowadays, is not recognized at an early age and the primary care clinician should have knowledge of its clinical spectrum in order to select appropriately the children who need further investigation for the diagnosis of this disorder.

Anemia and autoimmunity markers in an adolescent with Castleman disease.

We describe herein the case of an adolescent girl with anemia non-responsive to oral iron, associated with low-grade fever, diminished appetite and fatigue. A palpable mass below the xiphoid was noted. Laboratory findings were consistent with anemia of inflammation. Direct antiglobulin test was positive without any other evidence of autoimmune anemia. Other autoantibodies, such as anti-thyroid and anti-nuclear antibodies, were also positive. After thorough investigation, Castleman disease was the most likely diagnosis on the basis of high serum interleukin (IL)-6 and the magnetic resonance imaging findings. (18)F-FDG positron emission tomography-computed tomography showed a localized hypermetabolic mass, which was resected. Castleman disease of plasma type was identified on histology. Hemogloblin and IL-6 gradually returned to normal, whereas positive autoantibodies became negative. This case emphasizes the need to investigate thoroughly for the underlying cause of anemia of inflammation and to include Castleman disease in the differential diagnosis, on the measurement of IL-6.

Acalculous cholecystitis or biliary dyskinesia for Epstein-Barr virus gallbladder involvement?

We present two patients with Epstein-Barr virus (EBV) infection related to gallbladder involvement. Such an association is already known as EBV induced acalculous cholecystitis, diagnosed on the basis of ultrasonographic findings. In our patients, radioisotopic cholescintigraphy was also performed and it showed that gallbladder was visualized in both patients in contrast to that what can be observed in cases of cholecystitis. However, the value of ejection fraction was compatible with biliary dyskinesia. We, therefore, consider that impaired gallbladder contractility in EBV infection cases may actually represent biliary dyskinesia and not acalculous cholecystitis taking into account the radioisotopic findings and the self limited course of the disorder.

Controversial role of pets in the development of atopy in children.

BACKGROUND: Exposure to environmental allergens originating from different sources has been implicated in the sensitization to the respective allergens and development of atopic diseases. Keeping domestic animals is associated with exposure to relevant allergens but there are controversial data whether this exposure promotes or protects from the development of atopy. DATA SOURCES: We herein reviewed the literature regarding the available data for the exposure to pets (cats and/or dogs) and the development of atopy. For this purpose, we searched the PubMed database. RESULTS: This review attempts to answer the following questions that arise from the daily practice and the relevant studies, which are: a) is pet keeping associated with sensitization? b) is there an association between keeping pets and the development of asthma, allergic rhinitis and eczema, and, c) what is the underlying mechanism of any possible protective association? Despite the fact that several studies and meta-analyses have been conducted to explore the role of pets in the development of atopy, there are still conflicting pieces of evidence. It seems that there are different effects depending on the type of pets, the time and duration of exposure, and the genetic background of the individual. CONCLUSION: Further appropriately designed birth cohort studies are needed to explore whether exposure to relevant allergens from pets promotes or protects from the development of atopy.

The recent progress in RSV vaccine technology.

The most effective way to control RSV infection would be the development of an expedient and safe vaccine. Subunit vaccines, live attenuated RSV vaccines, plasmid DNA vaccines have been tested either in human or in mouse models without reaching the ultimate goal of efficacy and safety, at least in humans. Viruses such as adenovirus, sendai virus, measles virus were also used as vectors for the generation of RSV vaccines with promising results in animal models. Recent patents describe new techniques for the generation of candidate vaccines. These patents include virus like particles as vaccine platforms, recombinant RSVs or modified RSV F protein as component of the vaccine. Despite the number of the candidate vaccines, the new RSV vaccines should overcome many obstacles before being established as effective vaccines for the control of RSV infections especially for the young infants who are more susceptible to the virus.

HSV-2 meningitis disseminated from a herpetic whitlow.

HSV-2 meningitis is uncommon in childhood and is mainly associated with genital lesions or a history of sexual abuse. A 7-year-old boy with recurrent herpetic whitlow developed HSV-2 meningitis. HSV-2 was identified in the CSF by PCR. In children with herpetic whitlow, the risk of HSV-2, although rare, should be considered.

Severe jaundice in two children with Kawasaki disease: a possible association with Gilbert syndrome.

Kawasaki disease is a systemic vasculitis, mainly encountered in children. It may affect any organ. Acute cholestasis and severe obstructive jaundice is an atypical manifestation of the disease. We herein present two children with Kawasaki disease and severe direct hypebilibirunemia who also were homozygous and heterozygous respectively for the (TA)(7) promoter polymorphism of Gilbert syndrome. Intravenous immunoglobulin was administered to both patients at the acute phase of the disease and the fever remitted within 24 hr following the immunoglobulin administration. Furthermore oral aspirin at a dose of 80-100 mg/kg/24 hr was also given. The first child did not develop any coronary ectasia or aneurysm, whereas dilation of the right coronary artery was identified in the second child, one month after the disease onset. We discuss the possible contribution of Gilbert syndrome to the development of jaundice in our patients.

Miller-Fisher syndrome in association with enterovirus infection.

Miller-Fisher is a rare syndrome of childhood that presents with external ophthalmoplegia, ataxia, and areflexia. It has been mainly associated with a preceding Campylobacter infection and less commonly with other bacterial or viral infections. This report describes, for the first time, a child with Miller-Fisher syndrome and documented Enterovirus infection, as it was proven by the isolation of Enterovirus from cerebrospinal fluid by polymerase chain reaction testing.

Gilbert syndrome.

UNLABELLED: Gilbert syndrome is a common autosomal dominant hereditary condition with incomplete penetrance and characterized by intermittent unconjugated hyperbilirubinemia in the absence of hepatocellular disease or hemolysis. In patients with Gilbert syndrome, uridine diphosphate-glucuronyl transferase activity is reduced to 30% of the normal, resulting in indirect hyperbilirubinemia. In its typical form, hyperbilirubinemia is first noticed as intermittent mild jaundice in adolescence. However, Gilbert syndrome in combination with other prevailing conditions such as breast feeding, G-6-PD deficiency, thalassemia, spherocytosis, or cystic fibrosis may potentiate severe hyperbilirubinemia and/or cholelithiasis. It may also reduce plasma oxidation, and it may also affect drug metabolism. Although in general the diagnosis of the syndrome is one of exclusion, molecular genetic tests can now be performed when there is a diagnostic problem. The most common genotype of Gilbert syndrome is the homozygous polymorphism A(TA)7TAA in the promoter of the gene for UDP-glucuronosyltransferase 1A1 (UGT1A1), which is a TA insertion into the promoter designated UGT1A1*28. No specific management is necessary as Gilbert syndrome is a benign condition. CONCLUSION: Gilbert genotype should be kept in the clinician's mind, at least as a contributor factor, in cases with unexplained indirect hyperbilirubinemia.

Transient elevation of the ipsilateral hemidiaphragm associated with pneumonia.

Seventeen children with lobar or segmental pneumonia and ispilateral elevation of the diaphragm are described. These children did not differ significantly with respect to clinical and laboratory findings from their counterparts with pneumonia but without elevation of the hemidiaphragm. The elevation was transient and resolved by the time the repeat chest x-ray was taken six to eight weeks later.

Is Ceftriaxone-Induced Biliary Pseudolithiasis Influenced by UDP-Glucuronosyltransferase 1A1 Gene Polymorphisms?

Ceftriaxone (cfx), a third-generation cephalosporin antibiotic, leads to transient cholelithiasis in some children, also known as pseudolithiasis. However, the underlying pathogenetic mechanism of this adverse effect has not yet been elucidated. We describe 3 children with ceftriaxone-induced pseudolithiasis, who were also carriers of the A(TA)(7)TAA polymorphism of the UGT1A1 gene, implying that a cause and effect relation may exist.

The puzzling clinical spectrum and course of juvenile sarcoidosis.

BACKGROUND: Juvenile sarcoidosis is a rare, chronic, multisystem, granulomatous disease of obscure etiology which is seen in childhood and adulthood. The disease in childhood has a course different from that in adulthood. DATA SOURCES: PubMed database was searched using terms sarcoidosis, children or childhood sarcoidosis or juvenile sarcoidosis in combination with one of the following terms: epidemiology, clinical manifestations, genetics, diagnosis, treatment, and prognosis. We also retrieved the terms such as early onset sarcoidosis and Blau syndrome. Furthermore, e-medicine and European Respiratory Society monographs for sarcoidosis were reviewed. RESULTS: Sarcoidosis in childhood presents with two age dependent, distinct forms. In younger children it is clinically evident before the age of four years and characterized by the triad of rash, arthritis and uveitis. In their older counterparts, the juvenile late onset sarcoidosis involves several organs and its clinical appearance resembles the adult type of the disease, with the respiratory system being most frequently affected (hilar lymphadenopathy, pulmonary infiltrations). Steroid is the main agent of treatment whereas methotrexate is also used for beneficial steroid sparing effects. New, novel therapies may change the outcome of the disease especially in difficult morbid cases. CONCLUSIONS: Sarcoidosis in childhood is recognized as a systemic disease affecting various organs and having diverse clinical course depending on the age of onset.