Heikki Lukkarinen

Prednisolone reduces recurrent wheezing after first rhinovirus wheeze: a 7-year follow-up.

To better understand the role of human rhinovirus‐associated wheeze as a risk factor for childhood recurrent wheezing, a cohort of young children experiencing their first wheezing episode was followed until school age.

Neuroendocrine cell hyperplasia of infancy: a prospective follow-up of nine children

Neuroendocrine cell hyperplasia of infancy (NEHI) has recently been described as an obstructive airway disease that affects infants aged 1–24 months, and presents typically with tachypnoea, crackles and hypoxia. The pathogenesis of the disease is unknown. We describe the clinical course of nine infants with radiologically and histologically confirmed NEHI. Host or environmental factors were not associated with the disease development. All infants with lung function tests demonstrated findings consistent with severe irreversible peripheral airway obstruction, assessed with whole body plethysmography (6/6) or the rapid thoracoabdominal compression technique (5/5). While the symptoms abated in all infants, six infants developed a non-atopic asthma during the follow-up. Systemic or inhaled corticosteroid treatment did not affect the duration of the symptoms. NEHI may mimic severe asthma and thus this entity should be taken into account when evaluating infants with chronic respiratory symptoms.

CLOSTRIDIUM DIFFICILE RIBOTYPE 027-ASSOCIATED DISEASE IN CHILDREN WITH NOROVIRUS INFECTION

Two previously healthy children developed Clostridium difficile ribotype 027-associated disease concomitantly with norovirus infection. Viral gastroenteritis may contribute to epithelial homeostasis of the intestine and exacerbate the effects of toxins produced by C. difficile ribotype 027.

Cytokine profile and maternal depression and anxiety symptoms in mid-pregnancy—the FinnBrain Birth Cohort Study

Maternal prenatal psychological symptoms are associated with child health outcomes, e.g., atopic diseases. Altered prenatal functioning of the immune system is a potential mechanism linking maternal symptoms with child health. Research on prenatal distress and cytokines is warranted. The study population comprised consecutive N = 139 women from a general population-based FinnBrain Birth Cohort Study. Standardized questionnaires for depressive, overall anxiety, and pregnancy-related anxiety symptoms were used. Serum concentrations of selected cytokines were analyzed using Multiplex bead arrays from samples drawn at the gestational week 24. The concentrations of T helper (Th)2-related interleukins (IL)-9 and IL-13 and Th1-related IL-12 correlated positively with prenatal depressive and overall anxiety symptom scores (p values, range 0.011–0.029). Higher interferon (IFN)-γ/IL-4 ratio (p = 0.039) and Th2-related IL-5 (p = 0.007) concentration correlated positively with depressive symptoms. Pregnancy-related anxiety score correlated positively with IL-12 (p = 0.041), IL-13 (p = 0.025), and anti-inflammatory IL-10 (p = 0.048) concentrations. IL-6 and TNF-α concentrations were unrelated to prenatal symptoms. As a novel finding, we observed positive correlations between concentrations of potentially proallergenic cytokines and maternal prenatal psychological symptoms. Different symptom measures may yield distinct cytokine responses. This provides hypotheses for studies on mechanisms bridging prenatal stress and child health.

IFN-α/IFN-λ responses to respiratory viruses in paediatric asthma

We analysed the influence of rhinovirus (RV) in nasopharyngeal fluid (NPF) on type I and III interferon (IFN) responses (e.g. IFN-α and IFN-λ) and their signal transduction, at baseline and during disease exacerbation, in cohorts of pre-school children with and without asthma. At the time of recruitment into the Europe-wide study PreDicta, and during symptoms, NPF was collected and the local RV colonisation was analysed. Peripheral blood mononuclear cells (PBMCs) were challenged in vitro with RV or not. RNA was analysed by quantitative real-time PCR and gene arrays. Serum was analysed with ELISA for IFNs and C-reactive protein. We found that PBMCs from asthmatic children infected in vitro with the RV1b serotype upregulated MYD88, IRF1, STAT1 and STAT2 mRNA, whereas MYD88, IRF1, STAT1 and IRF9 were predominantly induced in control children. Moreover, during symptomatic visits because of disease exacerbation associated with RV detection in NPF, IFN-α production was found increased, while IFN-λ secretion was already induced by RV in asthmatic children at baseline. During asthma exacerbations associated with RV, asthmatic children can induce IFN-α secretion, indicating a hyperactive immune response to repeated respiratory virus infection. Asthma exacerbations associated with rhinovirus in children induce IFN-α and STAT1/STAT2 in PBMCs http://ow.ly/o14r303MW32

Influenza A Induced Acute Autonomic Neuropathy in an Adolescent

Influenza A may cause serious neurologic complications, but an autoimmune autonomic ganglionopathy has rarely been reported. Autoantibodies that impair synaptic transmission in the autonomic ganglia may cause orthostatic hypotension, gastrointestinal dysmotility, and sudomotor dysfunction. A 15-year-old girl developed severe and persisting orthostatic hypotension during influenza A infection. Removal of circulating antibodies by a single course of intravenous immunoglobulin resulted in rapid and complete recovery.

Recurrent sinus arrest and asystole due to breath-holding spell in a toddler; recovery with levetiracetam-therapy.

10-month-old girl was referred to our institution forevaluation of recurrent loss of consciousness that oc-curred for 30 seconds 1 to 3 times a day. The seizuresoccurred after crying, pain, or frustration. Because of tonic-like seizures before the loss of consciousness, the girl wasinitially remitted to pediatric neurology, where a movie-assisted electroencephalography was registered (Movie I ofthe online-only Data Supplement). When the girl was crying,she held breath, stiffened, and the recording showed asignificant bradycardia and a 30s asystole followed by flat-tening of assisted electroencephalography activity and loss ofconsciousness consistent with anoxia. Consciousness returnedrapidly after her cardiac function normalized. Between theseizures she was otherwise healthy and cardiac ultrasound andelectrocardiogram (ECG) were normal. Girl was diagnosed tosuffer from severe breath-holding spells.Ambulatory ECG demonstrated similar episodes daily anda treatment with atropine (8 g/kg, orally 3 times a day) wasinitiated by a pediatric cardiologist. Atropine did not signif-icantly affect the occurrence of the spells and pharmacolog-ical treatment was changed two months later to propranolol(0.4 mg/kg 3 times a day) without any significant improve-ment in the incidence of the spells. Since the girl wasoccasionally hurt by the falls caused by loss of consciousness,an off-label treatment with levetiracetam (8 mg/kg twice aday) was started. Levetiracetam did not affect the occurrenceof the breath-holding seizures, but after the treatment wasinitiated, breath-holding did not result in unconsciousness.Ambulatory ECG showed that her heart rate still slightlydecelerated during breath-holding, but no asystole was rec-orded. After the girl had been spell-free for 1 month,levetiracetam was discontinued and the symptoms reappearedwithin few days. Levetiracetam therapy was resumed and thesymptoms disappeared. However, because of the side-effects(hyperreactivity, aggressive behavior, and loss of appetite)the drug was eventually discontinued. As the symptoms weresevere, implantation of permanent pacemaker was warranted.Breath-holding spells is a relatively common disorder inyoungchildrenthatusuallyspontaneouslyresolvesandneedsnotreatment. The pathogenesis is incompletely understood, but animbalance between sympathetic and parasympathetic nervoussystem has been proposed.

Physical exercise increases nasal patency in asthmatic and atopic preschool children.

Background Physical exercise causes a decrease in nasal mucosal congestion and hence an increase in nasal patency. This nasal response has been studied only in adults. A correlation between nasal obstruction and asthma or allergic rhinitis has been previously found. This study evaluates the influences of atopy and asthma on nasal patency and the changes in nasal patency induced by physical exercise in preschool children. Methods An 8-minute exercise challenge test was conducted in 31 children aged between 4.1 and 6.4 years: 13 children had asthma, 17 were atopic, and 13 had neither asthma nor atopy. Nasal patency was measured with acoustic rhinometry at baseline and 10 minutes after the exercise. Results At baseline, the total acoustic values were 17–25% larger in nonasthmatic children than in asthmatic children. Accordingly, the acoustic values in nonatopic children were 16–35% larger than in atopic children. After physical exercise, there was an overall increase in mean total nasal volume from 2.973 (SD = 0.647) to 3.405 cm3 (SD = 0.705), indicating an improvement of 15% in nasal volume (p = 0.025). The increase in nasal patency was similar in asthmatic and nonasthmatic children, as well as in atopic and nonatopic children. Conclusion A significant increase in total nasal volume after physical exercise was found in all preschool children. The minimal cross-sectional areas remained smaller in asthmatic and atopic children after exercise, indicating partly irreversible nasal mucosal congestion in these children.

Contribution of repeated infections in asthma persistence from preschool to school age: Design and characteristics of the PreDicta cohort

The PreDicta cohort was designed to prospectively evaluate wheeze/asthma persistence in preschoolers in association with viral/microbial exposures and immunological responses. We present the cohort design and demographic/disease characteristics and evaluate unsupervised and predefined phenotypic subgroups at inclusion.

Inhaled Sargramostim Induces Resolution of Pulmonary Alveolar Proteinosis in Lysinuric Protein Intolerance

Pulmonary alveolar proteinosis (PAP) is a potentially fatal complication of lysinuric protein intolerance (LPI), an inherited disorder of cationic amino acid transport. The patients often present with mild respiratory symptoms, which may rapidly progress to acute respiratory failure responding poorly to conventional treatment with steroids and bronchoalveolar lavations (BALs). The pathogenesis of PAP in LPI is still largely unclear. In previous studies, we have shown disturbances in the function and activity of alveolar macrophages of these patients, suggesting that increasing the activity and the number of macrophages by recombinant human GM-CSF (rhuGM-CSF) might be beneficial in this patient group.Two LPI patients with complicated PAP were treated with experimental inhaled rhuGM-CSF (sargramostim) after poor response to maximal conventional therapy. BAL fluid and cell samples from one patient were studied with light microscopy and transmission electron microscopy.Excellent response to therapy was observed in patient 1 with no compliance problems or side effects. Macrophages with myelin figure-like structures were seen in her BAL sample. Slight improvement of the pulmonary function was evident also in patient 2, but the role of sargramostim could not be properly evaluated due to the complicated clinical situation.In conclusion, inhaled rhuGM-CSF might be of benefit in patients with LPI-associated PAP.