Intravenous magnesium sulfate for acute wheezing in young children: a randomised double-blind trial.

Magnesium sulfate has been shown to be an effective treatment in older children with asthma exacerbations, but it has not been investigated in acute severe virus-induced wheezing in young children.The study enrolled 61 children aged 6 months to 4 years. Inclusion criteria were severe wheezing, classified as a score of ≥6 points as assessed by the Respiratory Distress Assessment Instrument (RDAI) after initial treatment with salbutamol, and the symptoms of acute viral infection. The children were randomly allocated to receive either an infusion of magnesium sulfate (40 mg·kg-1) or 0.9% sodium chloride as a placebo infusion for 20 min. Primary outcome measure was mean change in RDAI scores from baseline to 6 h after the treatment.Change in the severity of wheezing from baseline to 6 h after the treatment, as measured by mean±sd RDAI scores, was 4.7±2.6 in the magnesium sulfate group and 4.2±4.2 in the placebo group (difference 0.5, 95% CI -1.3 to 2.3, p=0.594).Intravenous magnesium sulfate was ineffective in treating acute severe virus-induced wheezing in young children, in contrast to the previous efficacy demonstrated in older children.

NHLRC2 variants identified in patients with fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA): characterisation of a novel cerebropulmonary disease.

A novel multi-organ disease that is fatal in early childhood was identified in three patients from two non-consanguineous families. These children were born asymptomatic but at the age of 2 months they manifested progressive multi-organ symptoms resembling no previously known disease. The main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. In the affected children, neuropathology revealed increased angiomatosis-like leptomeningeal, cortical and superficial white matter vascularisation and congestion, vacuolar degeneration and myelin loss in white matter, as well as neuronal degeneration. Interstitial fibrosis and previously undescribed granuloma-like lesions were observed in the lungs. Hepatomegaly, steatosis and collagen accumulation were detected in the liver. A whole-exome sequencing of the two unrelated families with the affected children revealed the transmission of two heterozygous variants in the NHL repeat-containing protein 2 (NHLRC2); an amino acid substitution p.Asp148Tyr and a frameshift 2-bp deletion p.Arg201GlyfsTer6. NHLRC2 is highly conserved and expressed in multiple organs and its function is unknown. It contains a thioredoxin-like domain; however, an insulin turbidity assay on human recombinant NHLRC2 showed no thioredoxin activity. In patient-derived fibroblasts, NHLRC2 levels were low, and only p.Asp148Tyr was expressed. Therefore, the allele with the frameshift deletion is likely non-functional. Development of the Nhlrc2 null mouse strain stalled before the morula stage. Morpholino knockdown of nhlrc2 in zebrafish embryos affected the integrity of cells in the midbrain region. This is the first description of a fatal, early-onset disease; we have named it FINCA disease based on the combination of pathological features that include fibrosis, neurodegeneration, and cerebral angiomatosis.

Wheat oral immunotherapy was moderately successful but was associated with very frequent adverse events in children aged 6-18 years.

AIM: This study investigated oral immunotherapy (OIT) for children aged 6-18 years with wheat allergies. METHODS: Well-cooked wheat spaghetti was given to 100 children with wheat allergies every day for 17 weeks, increasing from 0.3 to 2000 mg of wheat protein, followed by three- and nine-month maintenance phases. Blood samples were taken before therapy and at follow-up visits. The study was carried out in 2009-2015 in four Finnish paediatric allergology units. RESULTS: The children (67% male) had a mean age of 11.6 years (range 6.1-18.6), and 57 were using wheat daily 16 months after the initiation of therapy. Allergic symptoms occurred in 94/100 children: mild in 34, moderate in 36 and severe in 24. Specific immunoglobulin E (IgE) for ω-5-gliadin was significantly higher in patients who did not reach the target dose and were related to the intensity of reactions. CONCLUSION: The majority (57%) of children with wheat allergies could use wheat in their daily diet 16 months after the initiation of OIT, but 94/100 had adverse reactions and 60 were moderate or severe. Specific IgE to ω-5-gliadin may provide a biomarker for how much wheat can be tolerated and the intensity of the reactions to immunotherapy.

School-age children enjoyed good respiratory health and fewer allergies despite having lung disease after preterm birth.

AIM: This study explored the under-researched area of whether preterm birth or bronchopulmonary dysplasia (BPD) affected hospitalisation rates, allergies or health-related quality of life (HRQoL). METHODS: We studied 88 schoolchildren born preterm at a mean gestational age of 28.8 weeks (range 24.1-31.9) and matched term-born controls at the mean age of 11 years (range 8-14). Hospitalisations after the first discharge were recorded, skin prick allergy tests were performed and HRQoL was assessed with a parental questionnaire. RESULTS: Preterm children were hospitalised more than controls (64% versus 39%, p = 0.001), mostly before two years of age. The adjusted odds ratios (OR) for two-year-old preterm-born children being hospitalised for wheezing was 8.2 (95% CI 2.0-34.1). BPD affected 56% of the preterm children, but did not influence hospitalisations, and the positive skin prick rate was similar between the preterm and term-born children (35% versus 48%, p = 0.126). Preterm BPD children had fewer positive skin prick tests than those without BPD. HRQoL was lower in preterm than term children (81.25 ± 10.84 versus 86.80 ± 9.60, p = 0.001). CONCLUSION: Most health problems experienced by preterm-born schoolchildren occurred before two years of age and were mainly wheezing disorders. BPD decreased atopy but had no influence on hospitalisation rates.

Cystic fibrosis patient characteristics and healthcare resource utilization in Finland using linked registries.

Background: Knowledge of prevalence and epidemiology of cystic fibrosis (CF) and healthcare resource use among Finnish people with CF is incomplete. Methods: We conducted a population-based matched cohort study using retrospective real-world data from linked Finnish national registries. Electronic healthcare data and drug purchases of 102 people with CF were analyzed between January 2015 and December 2019 (follow-up). A 5-fold control population was matched by sex, age, and place of residence. Comorbidities and medication use that occurred at any time during follow-up were assessed; annual rates of hospital service use were adjusted for follow-up. Results: The prevalence of CF in Finland was 1.85 per 100,000. Median age at diagnosis was 1 year, with 60 % diagnosed at age <2 years and 80 % at age <10 years. Median age at death in people with CF was 31.4 years (n < 5); no controls died. The most common comorbidities included chronic sinusitis (39.2 %), pneumonia (38.2 %), diabetes (20.6 %), and nasal polyps (18.6 %). The most purchased medications were antibiotics (99.0 %) and pancreatic enzymes (84.3 %). The annualized rate of hospital visits was higher in people with CF vs controls (outpatient: mean [SD], 17.4 [14.5] vs 0.9 [3.3]; median, 13.6 vs 0.4, respectively; inpatient: mean [SD], 1.0 [1.66] vs 0.03 [0.14]; median, 0.34 vs 0, respectively). Conclusions: The prevalence of CF in Finland is remarkably low, likely reflecting unique population characteristics and, in part, delayed diagnosis. Antibiotic use is frequent among Finnish people with CF. Inpatient hospital visits are >30 times higher in people with CF than matched controls.

Allergy in children: practical recommendations of the Finnish Allergy Programme 2008-2018 for prevention, diagnosis, and treatment.

The Finnish Allergy Programme 2008-2018 is a comprehensive plan intended to reduce the burden of allergies. One basic goal is to increase immunologic tolerance and change attitudes to encourage health instead of medicalizing common and mild allergy symptoms. The main goals can be listed as to: (i) prevent the development of allergic symptoms; (ii) increase tolerance to allergens; (iii) improve diagnostics; (iv) reduce work-related allergies; (v) allocate resources to manage and prevent exacerbations of severe allergies, and (vi) reduce costs caused by allergic diseases. So far, the Allergy Programme has organized 135 educational meetings for healthcare professionals around Finland. These meetings are multidisciplinary meetings gathering together all healthcare professionals working with allergic diseases. Since the start of the program in spring 2008, more than 7000 participants have taken part. Educational material for patient care has been provided on special Web sites/therapeutic portals, which can be accessed by all physicians caring for allergic patients. Local Allergy Working Groups have been created in different parts of Finland. As a part of the Programme, a set of guidelines for child welfare clinics was prepared. Child welfare clinics have a key role in the screening of illnesses and providing advice to families with a symptomatic child. The guidelines aimed to facilitate pattern recognition and clinical decision making for public health nurses and doctors are described in this paper.

Long-Term Results of Pediatric Congenital Pulmonary Malformation: A Population-Based Matched Case-Control Study with a Mean 7-Year Follow-Up.

Symptomatic congenital pulmonary malformations (CPMs) are a group of anomalies involving the lungs. The long-term outcomes of these patients are not well known. The present research aimed to study the pulmonary function, respiratory morbidity, and health-related quality of life (QoL) of patients treated for CPMs. All children (<16 years of age) treated for CPMs in 2002−2012 (in Oulu University Hospital) were invited to the follow-up visit. Altogether, there were 22 patients, out of which 17 (77%) participated. The mean follow-up time was 6.6 (ranged from 3 to 16) years. Pulmonary function tests, diffusing capacity, respiratory morbidity, and QoL were determined as the primary outcomes. Potential residual malformations and lung anatomy were investigated using computer tomography (CT) imaging. The outcomes were compared to the age- and sex-matched healthy controls. The forced expiratory volume at 1 s (FEV1, Z-score) remained lower in operated patients compared to the healthy controls (−1.57 ± SD 1.35 vs. −0.39 ± SD −0.86, p-value 0.005). There were no differences in respiratory morbidity or QoL between the patients and the controls. The surgical approach (lobectomy vs. partial resection) did not affect lung function. A younger age (<1 year of age) at the time of the surgery seemed to result in a higher lung capacity, but the finding was not statistically significant. Patients with CPMs treated with surgery were satisfied with their wellbeing in the long-term. A lower lung function did not have an impact on their wellbeing. However, there was a slight decrease in lung function compared to the healthy controls, and a clinical follow-up of the patients was recommended.

[Congenital ciliary dysfunction in children]. / Värekarvojen synnynnäiset toimintahäiriöt lapsilla.

Congenital ciliary dysfunctions are recessively inherited disorders. The disorder is poorly recognized, if the patient has no situs inversus. The diagnosis is delayed, being made on the average at the age of over five years. The review deals with a recent European multinational survey of the occurrence, genetics, diagnostics and treatment of congenital ciliary dysfunctions. Data of Finnish pediatric patients under treatment have also been collected for the survey. The number of congenital ciliary dysfunctions found in Finland is approximately one fifth of that found in other Nordic countries.

Contributing factors in self-poisoning leading to hospital admission in adolescents in northern Finland.

AIM: To evaluate the frequencies of different agents used in self-poisonings and acute factors contributing to intoxication of patients aged 12-18 years in northern Finland. MATERIAL: Retrospective medical record review of all hospitalized patients during the period from January 1, 1991 to December 31, 2006. OUTCOME MEASURES: Cause of the admission, contributing factors, readmissions within one year. RESULTS: There were 309 admissions during the period, 54% were females. The leading cause of admission was alcohol, in 222 cases (71.8%). Hospitalizations related to alcohol consumption were associated with accidental poisoning in recreational use. There were no acute contributing factors in the majority of all patients. Over one-third of all intoxications were intentional self-harm, although previously diagnosed psychiatric diseases were rare. CONCLUSIONS: It is crucial to recognize adolescent psychiatric disorders in time and consult child and adolescent psychiatrist in case of poisoning.

Cytokine responses in cord blood predict the severity of later respiratory syncytial virus infection.

BACKGROUND: It has been claimed that an early respiratory syncytial virus (RSV) infection can induce asthma and recurrent wheezing. OBJECTIVE: We addressed the question of whether infants contracting an early RSV infection differ from healthy children in their cytokine production at birth. METHODS: In a prospective cohort study cord blood samples were collected from 1084 newborns during autumn 2001. Of 47 of these newborns with subsequent virologically confirmed RSV infection before 6 months of age, 24 had enough cells for stimulation in cord blood samples (14 of those were hospitalized). Twenty-eight children had other respiratory virus infections (16 with enough cells), and samples from 48 healthy children of the 1084 total served as control specimens. Stimulated cytokine production of mononuclear cells was measured. The responses in the groups were evaluated by means of factor analysis. RESULTS: The infants hospitalized for RSV infection had higher LPS-stimulated combined IL-6 and IL-8 responses than the infants treated as outpatients (P = .005) or the healthy control subjects (P = .02). The hospitalized patients with RSV showed lower IL-1beta, IL-2, IL-4, IL-5, and IL-10 responses than those treated as outpatients (P = .02). High IL-6 and IL-8 responsiveness predicted a severe RSV infection (odds ratio, 2.20; 95% CI, 1.17-4.14; P = .01). The unstimulated cytokine responses at birth did not differ between the patients and healthy control subjects. CONCLUSION: The results suggest that natural differences in innate immunity predispose children to severe RSV infection rather than the infection modifying immune responses in childhood.

Risk factors for croup in children with recurrent respiratory infections: a case-control study.

Croup accounts for approximately 15% of all lower respiratory disease in children, but little is known about risk factors or its recurrence rate. The aim of this study was to determine the risk factors for croup and recurrent croup and to find out whether it is possible to predict the course of the disease. We considered croup patients who visited the Paediatric Department of Oulu University Hospital as primary health care patients at night during 1996-2000. For most analyses we used sex- and age-matched control patients who had had other respiratory infection but for environmental factors we used population controls. We performed conditional logistic regression analysis on data applying to 182 pairs of patients and controls. The recurrence rate was high, as 61% of the croup patients had had at least three episodes. Family history of croup was the most significant risk factor for both croup itself and recurrent croup. In multivariable analysis the odds ratio (OR) for the parents having a history of croup was 3.2 (95% CI 1.5, 7.1, P < 0.01) and 4.1 (95% CI 1.4, 11.7, P < 0.01) for recurrent croup. Parental smoking appeared to be a risk factor for respiratory infections but not for croup. Patients with croup had a cat as a pet less often than the controls, with OR 0.5 (95% CI 0.2, 1.0, P = 0.04). Family history appeared to be an exceptionally strong predictive factor for croup and its recurrence. In this patient series prone to respiratory infections recurrence of croup was common.

Structural Pulmonary Abnormalities Still Evident in Schoolchildren with New Bronchopulmonary Dysplasia.

BACKGROUND: A new pattern of bronchopulmonary dysplasia (BPD) has emerged with the improved survival of preterm children. OBJECTIVES: Our aim was to characterize structural abnormalities associated with new BPD and to evaluate whether the severity of high-resolution computed tomography (HRCT) changes is associated with lung function. METHODS: HRCT scans were performed on 21 schoolchildren with a history of new BPD (mild, n = 9; moderate, n = 4; and severe, n = 8) with a mean age of 12.7 years (range: 8.7-16.7). Scans were interpreted by 2 radiologists using a structured scoring system. Spirometry (forced expiratory volume in 1 s [FEV1] and maximum mid-expiratory flow [MMEF]) and the diffusion capacity of the lung for carbon monoxide (DLCO) were measured. RESULTS: At least 1 HRCT abnormality was evident in 17 children (81%), including linear-to-triangular subpleural opacities (71%), air trapping (29%), mosaic perfusion (24%), peribronchial thickening (14%), and emphysema (14%). The HRCT score was higher in the severe BPD group (11.50; 95% CI 2.86-20.14) than in the mild or moderate BPD group (1.39; 95% CI 0.24-2.54, and 2.75; 95% CI 0.28-5.22, respectively). HRCT scores were inversely related to FEV1 (ß -4.23; 95% CI -6.97 to -1.49, p = 0.004) and MMEF (ß -3.45; 95% CI -6.10 to -0.80, p = 0.013) but not to DLCO. The duration of the initial mechanical ventilation was associated with HRCT scores (p = 0.014). CONCLUSIONS: Structural lung abnormalities are common among schoolchildren with a history of new BPD, resembling abnormalities described in the presurfactant era. HRCT abnormalities are associated with the duration of early mechanical ventilation and the severity of BPD and they are correlated with spirometry.

Infections in child day care centers and later development of asthma, allergic rhinitis, and atopic dermatitis: prospective follow-up survey 12 years after controlled randomized hygiene intervention.

OBJECTIVE: To evaluate the effect of successful prevention of common infections in child day care centers on the later development of allergic diseases. DESIGN: Prospective follow-up survey with a questionnaire administered 12 years after a controlled randomized hygiene intervention. SETTING: Twenty municipal child day care centers in Oulu, Finland. PARTICIPANTS: A questionnaire was sent to 1354 prior participants (98%) in the intervention trial. The response rate was 68% (928 of 1354 participants). MAIN INTERVENTION: Hygiene intervention from March 1, 1991, to May 31, 1992. MAIN OUTCOME MEASURES: The number of respondents who had a diagnosis of asthma, allergic rhinitis, and/or atopic dermatitis made by a physician, and the number of those who reported symptoms of atopic diseases. RESULTS: Asthma was diagnosed by a physician in 48 of the 481 respondents (10%) from the intervention child day care centers, with markedly fewer infections, and in 46 of the 447 controls (10%) (relative risk, 1.0; 95% confidence interval, 0.7-1.4). Similarly, no differences were found in the numbers of children who had a diagnosis of other atopic diseases or who had reported such symptoms. CONCLUSION: The prevention of common respiratory tract and enteric infections during early childhood does not change later allergic morbidity.

Intrauterine growth restriction predicts lower lung function at school age in children born very preterm.

OBJECTIVE: Children born preterm have lower lung function compared with term-born children. Intrauterine growth restriction (IUGR) may predispose individuals to chronic obstructive pulmonary disease. The purpose of this observational study was to investigate the role of IUGR as predictor of lung function at school age in children born very preterm. We further studied the difference in lung function between term-born and preterm-born children with distinct morbidities. DESIGN: Preterm-born children and age-matched and sex-matched term-born comparison groups (88 of each) were studied at the mean age of 11 years. Spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) were recorded. All preterm-born subjects with IUGR (n=23), defined as birth weight less than -2 SD, were compared with preterm-born subjects without IUGR (n=65). RESULTS: In the preterm-born children exposed to IUGR, the forced expiratory volume in 1 s (FEV1) was 5.7 (95% CI -10.2 to -1.3) and DLCO 9.2 percentage points lower (95% CI -15.7 to -2.7) than in the preterm-born children with appropriate in utero growth (expressed as percentage of predicted values). The effect of IUGR in decreasing FEV1 and DLCO remained significant after adjustment for bronchopulmonary dysplasia (BPD). Further study indicated that after adjustment with IUGR and BPD, prematurity explained reduction in FEV1 but not in DLCO. CONCLUSIONS: In children born very preterm, IUGR is an independent risk factor for a lower lung function in school age. We propose that IUGR and BPD are the major early factors predisposing the children born very preterm to lower lung function.

New BPD predicts lung function at school age: Follow-up study and meta-analysis.

New treatment practices have improved survival of preterm infants and decreased airway pathology in bronchopulmonary dysplasia (BPD). Our aim was to investigate whether preterm birth, BPD, and the severity of BPD predict lung function in school children that are born in surfactant era. We studied pulmonary function of 88 school-aged children born very preterm (gestational age <32 weeks) and paired them with 88 age- and sex-matched controls born at term. Spirometry and diffusion capacity were recorded. We also performed a meta-analysis covering the era of antenatal corticosteroid and surfactant treatment. BPD was defined as oxygen dependence for ≥ 28 days and it was severity-graded by oxygen requirement at 36 weeks postmenstrual age (mild, none; moderate, FiO2 = 0.22-0.29; severe, FiO2 ≥ 0.30). Preterm children had lower forced expiratory volume in 1 sec (FEV1 ) 86.4 ± 11.8 versus 94.9 ± 10.1 (mean % predicted ± SD; P < 0.001), and lower diffusion capacity (DLCO) 87.6 ± 13.9 versus 93.7 ± 12.0 (P = 0.005) compared with term controls. BPD group differed in both FEV1 (P = 0.037) and DLCO (P = 0.018) from those without BPD. For meta-analysis, search identified 210 articles. Together with present results, six articles met the inclusion criteria. FEV1 of no BPD, all BPD, and moderate to severe BPD groups differed from that in term controls by -7.4, -10.5, and -17.8%, respectively. According to meta-analysis and follow-up study, the adverse effects of prematurity on pulmonary function are still detectable in school-age. BPD was associated with reductions in both diffusion capacity and spirometry. New interventions are required to document a further decrease in the life-long consequences of prematurity.