Serum biomarkers in neuroendocrine cell hyperplasia of infancy.

BACKGROUND: Neuroendocrine cell hyperplasia of infancy (NEHI) is a form of childhood interstitial lung disease of unknown origin associated with hyperplasia of pulmonary neuroendocrine cells (PNECs). Diagnosis is based on the characteristic clinical picture and typical radiological imaging, and, in some cases, on lung biopsies. To date, no biochemical indicators of the disease have been identified. AIM: We aimed to determine biomarkers that could be useful in the management of children diagnosed with NEHI. METHODS: Patients with NEHI and healthy children were enrolled. Concentrations of serum biomarkers secreted by PNECs (calcitonin gene-related peptide and gastrin-releasing peptide) and biomarkers of the destruction of alveolar capillary membrane (surfactant proteins A and D [SP-A and SP-D]; glycoprotein Krebs von den Lungen-6 [KL-6]; metalloproteinases 7 and 9 [MMP-7 and MMP-9]; tissue inhibitor of metalloprotease 1) were measured. RESULTS: Fifty-two children with NEHI and 23 healthy children were included in the study. The median age of children with NEHI was 3.9 years. There were no differences in serum levels of biomarkers secreted by PNECs between groups. KL-6 levels were significantly higher in children with NEHI than in healthy ones (median 119.6 vs. 92.1 U/mL, p = 0.003); however, concentrations of KL-6 were low in both groups. No significant differences existed between groups for the remaining biomarkers associated with the destruction of the alveolar-capillary membrane. CONCLUSIONS: Measurement of serum biomarkers released by PNECs and those associated with the destruction of the alveolar-capillary membrane does not appear to be useful in the management of children with NEHI.

The outcomes of COVID-19 pneumonia in children-clinical, radiographic, and pulmonary function assessment.

OBJECTIVES: The goal of this study was to assess the pulmonary sequelae of COVID-19 pneumonia in children. STUDY DESIGN: Children (0-18 years old) diagnosed with COVID-19 pneumonia hospitalized between March 2020 and March 2021 were included in this observational study. All children underwent follow-up visits 3 months postdischarge, and if any abnormalities were stated, a second visit after the next 3 months was scheduled. Clinical assessment included medical history, physical examination, lung ultrasound (LUS) using a standardized protocol, and pulmonary function tests (PFTs). PFTs results were compared with healthy children. RESULTS: Forty-one patients with COVID-19 pneumonia (severe disease n = 3, mechanical ventilation, n = 0) were included in the study. Persistent symptoms were reported by seven (17.1%) children, the most common was decreased exercise tolerance (57.1%), dyspnea (42.9%), and cough (42.9%). The most prevalent abnormalities in LUS were coalescent B-lines (37%) and small subpleural consolidations (29%). The extent of LUS abnormalities was significantly greater at the first than at the second follow-up visit (p = 0.03). There were no significant differences in PFTs results neither between the study group and healthy children nor between the two follow-up visits in the study group. CONCLUSIONS: Our study shows that children might experience long-term sequelae following COVID-19 pneumonia. In the majority of cases, these are mild and resolve over time.

Pulmonary function in children with persistent tachypnea of infancy.

BACKGROUND: Data on the prevalence and type of lung function impairment in preschool and school-aged children previously diagnosed with persistent tachypnea of infancy (PTI) are scarce. Therefore, this study aims to assess pulmonary function in this age group. METHODS: Children diagnosed with PTI over 3 years old were admitted for follow-up visits and healthy controls were enrolled. The study group included children who were able to complete pulmonary function tests (PFTs). Medical history, physical examination, and pulmonary function (spirometry, body plethysmography, impulse oscillometry, nitrogen multiple breath washout test, diffusing capacity for carbon monoxide [DLCO ]) were assessed. RESULTS: Thirty-seven children (26 boys, 11 girls; median age: 5.6 years) diagnosed with PTI and 37 healthy controls were recruited. Forced expiratory volume in 1 s and forced vital capacity were significantly lower (-1.12 vs. 0.48, p = 0.002 and -0.83 vs. 0.31, p = 0.009, respectively); respiratory resistance at 5 Hz (0.06 vs. -0.62, p = 0.003), resonant frequency (1.86 vs. 1.36, p = 0.04), residual volume (RV) (2.34 vs. -1.2, p < 0.0001), RV%TLC (total lung capacity) (2.63 vs. -0.72, p < 0.0001), and specific airway resistance (5.4 vs. 2.59, p = 0.04) were significantly higher in PTI patients as compared with controls (data were presented as median z-score). Air trapping was found in 60.0%, and abnormally high lung clearance index and DLCO  were found in 73.3% and 90.9% of PTI patients, respectively. CONCLUSIONS: This study demonstrated that lung function is affected in most children with PTI. PFTs showed that peripheral airways are the major zone of functional impairment.

Diagnostic accuracy of peripheral lung function measurements in paediatric asthma control assessment: a pilot study.

Introduction: Recent studies have indicated the significance of the peripheral airways in asthma control. Methods estimating airway resistance, air trapping, and ventilation inhomogeneity are useful for assessing this area of the lung and have proven utility in the evaluation of asthma; however, it is unclear which method is most effective at characterising uncontrolled asthma. Aim: To evaluate the diagnostic accuracy of various peripheral airway function measurements in the assessment of asthma control in children. Material and methods: Children with controlled (n = 35) and uncontrolled (n = 29) asthma performed a sequence of pulmonary function tests (i.e. spirometry, body plethysmography, oscillometry, nitrogen washout test, and exhaled nitric oxide). The diagnostic accuracy of each peripheral airway measure was evaluated by an area under the receiver operating characteristic curve (AUC). Results: Most peripheral airway parameters were significantly increased in children with uncontrolled asthma compared with children with controlled asthma. The measures with the highest diagnostic accuracy for asthma control were lung clearance index (LCI) (AUC = 0.76), with high specificity (0.97) and modest sensitivity (0.46), acinar ventilation heterogeneity (Sacin) (AUC = 0.73), with high sensitivity (0.85) and modest specificity (0.54), and resonance frequency (Fres) (AUC= 0.74), with perfect specificity (1.0) but low sensitivity (0.38). Conclusions: LCI, Sacin and Fres had the highest discriminative capacity for distinguishing children with controlled and uncontrolled asthma among all evaluated peripheral airways measures. Discrepancies in the performance (i.e. sensitivity and specificity) of each parameter suggest that a combination may be most effective in determining asthma control status.

Peripheral airways involvement in children with asthma exacerbation.

OBJECTIVE: The literature provides some evidence of peripheral airways key role in the pathogenesis of asthma. However, the extent to which lung periphery including acinar zone contribute to asthma activity and control in pediatric population is unclear. Therefore, the aim of the study was to estimate peripheral airways involvement in children with asthma exacerbation and stable asthma simultaneously via different pulmonary function tests. METHODS: Children with asthma exacerbation (n = 20) and stable asthma (n = 22) performed spirometry, body plethysmography, exhaled nitric oxide, impulse oscillometry (IOS), and multiple-breath washout (MBW). RESULTS: Peripheral airway's function indexes were increased in children with asthma, particularly in group with asthma exacerbation when compared with stable asthma group. The prevalence of abnormal results was significantly higher in asthma exacerbation. All children with asthma exacerbation had conductive ventilation inhomogeneity; 76% had acinar ventilation inhomogeneity. According to IOS measurements, resistance and reactance were within normal range, but other IOS parameters were significantly higher in children with asthma exacerbation compared with stable asthma group. The 36% of children with acute asthma had air trapping. CONCLUSION: Significant involvement of peripheral airways was observed in children with asthma, particularly in asthma exacerbation, which determine lung periphery as important additional target for therapy and provide new insights into pathophysiological process of pediatric asthma.

The improved clinical course of persistent tachypnea of infancy with inhaled bronchodilators and corticosteroids.

BACKGROUND: Persistent tachypnea of infancy (PTI) is the most common interstitial lung disease in young children. As no standardized therapeutic guidelines exist, different pharmaceuticals are used to treat PTI; inhaled corticosteroids (ICS) and bronchodilators being mostly used. This observation assessed the effectiveness of bronchodilators and ICS in children with PTI enrolled in the children's interstitial lung diseases (chILD)-EU Register. METHODS: Symptomatic children with PTI were observed according to a predetermined stepwise protocol including bronchodilators as the first choice treatment (6 weeks). In patients with incomplete response, additionally, ICS was given (12 weeks). Signs, symptoms, and pulmonary function were evaluated at three time points: at baseline, 6 (±1) weeks after initiation of bronchodilators, and 12 (±1) weeks after bronchodilators/ICS. RESULTS: Thirty-one children (median age: 44 months, interquartile range [IQR]: 15-67) were included. The therapy was associated with a significant reduction of tachypnea (53.3% of patients, p = 0.02), exercise intolerance (52.2% of patients, p < 0.001), chest retractions (43.8% of patients, p = 0.04), and crackles (29.2% of patients, p = 0.02). Also, a significant improvement in forced expiratory volume in 1 s (FEV1 ) (median z score: -2.21 vs. -0.47, p = 0.03), residual volume (RV) (median z score 5.28 vs. 1.07, p = 0.007), RV% total lung capacity (TLC) (median z score: 6.05 vs. 1.48, p = 0.01), sRaw (median z score: 6.6 vs. 4.64, p = 0.01), R5 (median z score: 1.27 vs. 0.31, p = 0.009), and R5-R20 (median: 0.58 vs. 0.26 kPa/(l/s), p = 0.002) was demonstrated. CONCLUSIONS: Inhaled bronchodilators and ICS may exert a positive effect on the severity of symptoms and pulmonary function test (PFT) in symptomatic children with PTI. However, a randomized control trial should be conducted to confirm their effectiveness.

Periostin concentration in exhaled breath condensate in children with mild asthma.

OBJECTIVE: Periostin is considered to be a marker of eosinophilic inflammation in patients with asthma. However, there are no literature data on exhaled breath condensate (EBC) periostin level in pediatric patients with asthma. The aim of this study was to analyze EBC periostin concentration in children with mild asthma and to evaluate the potential usefulness of EBC periostin level as a biomarker for the disease. METHODS: EBC and serum periostin concentrations were measured by enzyme-linked immunosorbent assay in 23 children with asthma and 23 healthy controls. RESULTS: EBC periostin concentration was 250- to 780-fold lower than that found in serum. No significant differences between serum nor EBC periostin concentration in asthmatics and the control group were showed. The comparison between children with Th2 and non-Th2 type of asthma did not show significant differences in periostin concentration, both in serum and EBC. Serum periostin concentration inversely correlated with BMI and age not only in asthma patients but also in controls. CONCLUSIONS: In children with mild asthma, periostin may be measured not only in serum but also in EBC. The low periostin level in patients with mild asthma and lack of difference between asthmatic subjects and controls indicate that EBC periostin may not be useful as an asthma biomarker in this group.

Glomerular filtration rate in patients with obstructive sleep apnea: the influence of cystatin-C-based estimations and comorbidity.

BACKGROUND: Recent studies indicate that chronic kidney disease (CKD) is a comorbidity in patients with obstructive sleep apnea (OSA). We hypothesized that the use of the classical muscle-dependent, creatinine-based equation to estimate glomerular filtration rate (GFR) in patients with OSA may be inaccurate due to the extreme body mass index (BMI) of some patients. The aim of this study was to establish the role of cystatin-C-based estimation of GFR for the detection of CKD in patients with OSA and typical comorbidities. METHODS: Two hundred and forty consecutive patients with newly diagnosed OSA were enrolled into this cross-sectional study. In all patients estimated GFR (eGFR) was calculated with chronic kidney disease-epidemiology collaboration group (CKD-EPI) equations using creatinine and cystatin-C. All patients were examined for comorbidities. RESULTS: In obese patients with OSA significant differences between GFR estimations based on creatinine and cystatin were found: eGFR based on muscle-dependent creatinine measurement was significantly higher than the muscle-independent eGFR based on cystatin-C measurement. CONCLUSIONS: GFR can be routinely screened for using creatinine-based estimations (eGFRcreat). In a selected group of patients with OSA with BMI over 30 kg/m2 the addition of cystatin-C for assessment of eGFR is suggested.

The Influence of National Guidelines on the Management of Community-Acquired Pneumonia in Children. Do Pediatricians Follow the Recommendations?

This is a retrospective study whose main objective was to analyze the influence of the Polish Guidelines for the Management of Respiratory Tract Infections of 2010 (PGMRTI) on in-hospital treatment of children with community-acquired pneumonia (CAP). Files from four Warsaw hospitals were reviewed to identify children with uncomplicated CAP, treated before (2008-2009) (pre-PGMRTI) and after (2011-2012) (post-PGMRTI) publication of the guidelines. Predefined data on the management were compared. A cohort of 2,359 children (1,081 pre-PGMRTI and 1,278 post-PGMRTI) was included. We found that co-amoxiclav was the most common first-line therapy in children >3 months of age (34.6% and 40.4% pre- and post-PGMRTI, respectively), followed by cefuroxime (31.8% and 20.9% pre- and post-PGMRTI, respectively; p < 0.0001) and macrolides (17.4% and 24.5% pre- and post-PGMRTI, respectively; p < 0.0001). Amoxicillin was rarely used (5.4% and 4.9%, pre- and post-PGMRTI, respectively). The study revealed an overuse of inhaled bronchodilators, corticosteroids, and mucoactive drugs. Blood diagnostic tests were applied to a significant percentage of patients: blood cultures (41.2% and 44.5% pre-and post-PGMRTI, respectively) and serology for atypical pathogens (27.9% and 44.9% pre-and post-PGMRTI, respectively; p < 0.0001). The number of follow-up chest X-rays increased (30.5% and 53.8% pre- and post-PGMRTI, respectively; p < 0.0001). In conclusion, the study demonstrates an unsatisfactory influence of the guidelines on in-hospital management of CAP in children. Despite an explicit recommendation for the use of amoxicillin, it was still underused. Other methods of education and guideline dissemination are needed to optimize the prescribing of antibiotics.

Risk factors for local complications in children with community-acquired pneumonia.

AIM: The aim of this study was to evaluate the factors that could predict the development of local complications (parapneumonic effusion/pleural empyema, necrotizing pneumonia, and lung abscess) in children with community-acquired pneumonia (CAP). METHODS: Demographic, clinical, and laboratory data were prospectively collected and compared in children with noncomplicated and complicated CAP. RESULTS: Two-hundred and three patients aged from 2 months to 17 years were enrolled. There were 141 and 62 children with noncomplicated and complicated CAP, respectively. Significantly longer duration of fever and a higher level of acute phase reactants were demonstrated in complicated when noncomplicated to complicated CAP. Asymmetric chest pain as well as prehospital treatment with ibuprofen and acetaminophen were significantly more common in patients with complicated CAP (P < .001, P = .02 and P = .003, respectively). Preadmission cumulative dose of ibuprofen exceeding 78.3 mg/kg (median dose for the entire group) was associated with 2.5-fold higher odds ratio (OR) for CAP complications [OR 2.54 CI (1.31-4.94); P = .008)]. In contrast, pneumococcal vaccination was associated with lower odds ratio [OR.03 CI (.23-.89); P = .03] for local complications. CONCLUSIONS: Some clinical and laboratory data including chest pain, longer duration of fever, higher acute phase reactants, and especially preadmission treatment with ibuprofen or acetaminophen were associated with local complications of CAP. The results of this study highlight the association between the dose of ibuprofen and local CAP complications.

The influence of comorbidities on mortality in sarcoidosis: a observational prospective cohort study.

AIM: The aim of this study was to identify the frequency and prevalence of comorbidities in sarcoid patients and to assess their influence on overall mortality in the cohort of patients with sarcoidosis. MATERIALS AND METHODS: A cohort of 557 patients with histologically confirmed sarcoidosis diagnosed between 2007 and 2011 and a group of non-sarcoid controls were observed. All patients were carefully observed for comorbidities and mortality. RESULTS: 291 males (52.2%) and 266 females (47.8%) with mean age 48.4 ± 12.0 years in sarcoidosis group and a group of 100 controls with mean age (49.25 ± 10.3) were observed. The mean number of comorbidities in both groups was similar (0.9 ± 0.99 vs 0.81 ± 0.84 NS). The frequency of thyroid disease was significantly higher in sarcoidosis group comparing to controls at the time of diagnosis (OR = 3.62 P = 0.0144). During the observation period (median 58.0 months), 16 patients died (2.9%). The mean number of comorbidities was significantly higher in the groups of non-survivors as compared to survivors (2.8 ± 1.0, vs 0.8 ± 0.9), P < 0.0001. CONCLUSION: The comorbidity burden has strong impact on mortality in sarcoidosis. Thyroid diseases are more frequent in sarcoidosis than in non-sarcoid controls.

Abnormalities in lung volumes and airflow in children with newly diagnosed connective tissue disease.

INTRODUCTION: Connective tissue diseases (CTDs) of childhood are rare inflammatory disorders, involving various organs and tissues including respiratory system. Pulmonary involvement in patients with CTDs is uncommon but may cause functional impairment. Data on prevalence and type of lung function abnormalities in children with CTDs are scarce. Thus, the aim of this study was to asses pulmonary functional status in children with newly diagnosed CTD and follow the results after two years of the disease course. MATERIAL AND METHODS: There were 98 children (mean age: 13 ± 3; 76 girls), treated in Department of Pediatric Rheumatology, Institute of Rheumatology, Warsaw and 80 aged-matched, healthy controls (mean age 12.7 ± 2.4; 50 girls) included into the study. Study procedures included medical history, physical examination, chest radiograph and PFT (spirometry and whole body-plethysmography). Then, the assessment of PFT was performed after 24 months. RESULTS: FEV1, FEV1/FVC and MEF50 were significantly lower in CTD as compared to control group, there was no difference in FVC and TLC. The proportion of patients with abnormal lung function was significantly higher in the study group, 41 (42%) vs 9 (11%). 24-months observation didn't reveal progression in lung function impairment. CONCLUSIONS: Lung function impairment is relatively common in children with CTDs. Although restrictive ventilatory pattern is considered typical feature of lung involvement in CTDs, airflow limitation could also be an initial abnormality.

The Influence of the Reference Values on the Interpretation of Lung Function in Children: Comparison of Global Lung Initiative 2012 and Polish 1998 Reference Values.

Interpretation of spirometry strongly depends on the applied predicted values. New Global Lung Initiative (GLI) reference values have recently been published but their influence on spirometry interpretation in children has not been widely evaluated. The aim of the study was to compare the interpretation of spirometry using GLI-2012 vs. Polish-1998 reference values. Spirometry results of 315 Caucasian children aged 4-18 were analyzed. Airway obstruction was defined as FEV1/FVCLLN. The findings were that FEV1 and FVC expressed as GLI-2012 or Polish-1998 z-scores differed significantly (p<0.05). The mean FEV1 z-score was -0.68±1.25 vs. -0.13±1.70 and the mean FVC was -0.34±1.08 vs. 0.30±1.15 for GLI-2012 and Polish-1998, respectively. There was no difference for FEV1/FVC z-scores. Obstructive and restrictive ventilatory patterns were diagnosed in 20.3% and 7.6% children using GLI-2012 values compared with 17.5% and 3.8% when using Polish-1998 reference values, respectively. In conclusion, the use of GLI-2012 reference values in the population of Polish children increases the number of detected lung function abnormalities compared with Polish-1998 reference values.

Necrotizing Pneumonia and Its Complications in Children.

Necrotizing pneumonia (NP) is an emerging complication of community acquired pneumonia (CAP) in children. This study aimed at the evaluation of etiology, clinical features, treatment, and prognosis of NP. The institutional database of children with CAP treated between April 2008 and July 2013 was searched to identify children with NP. Then, data on the NP characteristics were retrospectively reviewed and analyzed. We found that NP constituted 32/882 (3.7%) of all CAPs. The median age of children with NP was 4 (range 1-10) years. The causative pathogens were identified in 12/32 children (37.5%) with Streptococcus pneumoniae being the most common (6/32). All but one patient developed complications: parapneumonic effusion (PPE), pleural empyema or bronchopleural fistula (BPF), which required prompt local treatment. The median duration of hospital stay and antibiotic treatment was 26 (IQR 21-30) and 28 (IQR 22.5-32.5) days, respectively. Despite severe course of the disease no deaths occurred. A follow-up visit after 6 months revealed that none of the patients presented with any signs and symptoms which could be related to earlier pneumonia. Chest radiographs showed complete or almost complete resolution of pulmonary and pleural lesions in all patients. We conclude that necrotizing pneumonia is a relatively rare but severe form of CAP that is almost always complicated by PPE/empyema and/or BPF. It can be successfully treated with antibiotics and pleural drainage without major surgical intervention.

Low prevalence of pulmonary involvement in children with inflammatory bowel disease.

BACKGROUND: Since extraintestinal sites of inflammation have been demonstrated in patients with Crohn's disease (CD) and ulcerative colitis (UC), both entities are regarded as systemic disorders. There are only scarce data on the prevalence of inflammatory bowel disease (IBD)-associated lung involvement in children. OBJECTIVES: The aim of our study was to investigate pulmonary involvement in pediatric patients with IBD. MATERIAL AND METHODS: Fifty children with IBD (25 UC and 25 CD, mean age 14.2 ± 3.2 yrs) and 39 age-matched, healthy, control subjects were included in the study. Pulmonary function testing, methacholine bronchial challenge, fractional exhaled nitric oxide (FeNO) and high resolution computed tomography (HRCT) were used to detect functional and/or structural pulmonary involvement. RESULTS: There were no differences in spirometric parameters, lung volumes or lung diffusion capacity for carbon monoxide between IBD patients and control subjects. Highly significant differences were found in FeNO between CD, UC and control patients (mean 9.3 ± 3.3, 27.7 ± 14.8 and 16.6 ± 9.28, respectively; p = 0.000). Bronchial hyperresponsiveness was diagnosed in six IBD cases (14.6%). HRCT (performed in 32 patients from the study group) revealed mild bilateral bronchiectasis in one patient. CONCLUSIONS: The prevalence of pulmonary involvement in children with IBD is low. Screening for pulmonary involvement in children and young adults with IBD may enable early detection of IBD-related pulmonary diseases which, seems to be notably more common in adult patients. Elevated FeNO could probably be regarded as a marker of airway involvement in non-smoking UC pediatric patients. This requires further studies.

Local treatment of empyema in children: a systematic review of randomized controlled trials.

UNLABELLED: The aim of the study is to systematically evaluate data from randomized controlled trials (RCTs) on the efficacy of using intrapleural fibrinolytic agents in the treatment of complicated parapneumonic effusions or empyema in children. The Cochrane Library, MEDLINE and EMBASE databases were searched in July 2009. Four RCTs, involving 194 children, were included. In two RCTs, intrapleural fibrinolytic treatment was compared with normal saline. One of these RCTs showed a significantly reduced hospital stay in those treated with urokinase compared with those treated with normal saline. Otherwise, no fibrinolytic agent had an effect on any other outcome. Two RCTs that compared fibrinolytic treatment with video-assisted thoracoscopic surgery (VATS) revealed no benefit of VATS. CONCLUSION: There is little evidence that intrapleural fibrinolysis is more effective than normal saline in the local treatment of complicated parapneumonic effusions or empyema in children. There is no evidence that VATS is more effective than fibrinolytic treatment. Only a limited number of trials were available for analysis, so some caution must be exercised in interpreting the strength of the evidence presented.

Parental tobacco smoking is associated with augmented IL-13 secretion in children with allergic asthma.

BACKGROUND: Exposure to environmental tobacco smoke (ETS) has been shown to increase symptoms of allergic bronchial asthma, but direct effects on the expression of inflammatory markers have not been demonstrated thus far. OBJECTIVE: The aim of this study was to assess the correlation of ETS exposure with the expression of proinflammatory mediators in airway secretions, including IFN-gamma and IL-12, as well as IL-5 and IL-13, in allergic asthmatic schoolchildren and healthy control subjects. METHODS: By using the nasopharyngeal aspiration technique, airway secretions were collected from 24 atopic children with asthma (age, 6-16 years) and 26 healthy control subjects, and the concentration of cytokines was measured with immunoenzymatic methods. RESULTS: IL-13 levels were highly increased in patients with asthma (P < .005), and parental tobacco smoke resulted in a significant increase in airway IL-13 secretion in these children compared with that seen in nonexposed children and healthy control subjects (median, 860 pg/mL vs 242 pg/mL and 125 pg/mL, respectively). Furthermore, a positive correlation between IL-13 levels and serum IgE concentrations (r(s) = 0.55) was found in children with allergic asthma. CONCLUSIONS: These results indicate that ETS augments the expression and secretion of IL-13 in allergic asthma and that nasopharyngeal aspiration is a suitable method to assess cytokine measurements in airways in children. Measurements of IL-13 in secretions might be taken into account as a noninvasive marker of airway inflammation and to assess the detrimental effects of ETS.